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Journal:	Journal of Urology
Authors:	Walsh PC, Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, Reuter VE, Venkatraman ES, Leibel SA.	Issue:	2001, 166: 876-881

Title:

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localised prostate cancer

Abstract:
This paper reports the results in terms of outcome and tolerance of 3D conformal and intensity modulated radiation therapy for localised prostate cancer. This technique uses new algorithms for dose calculations, and computer aided optimisation to generate treatment plans that conform to the prescribed dose to the prostate, thus attempting to exclude adjacent normal organs from harmful irradiation. This technique is only available at present in a limited number of centres. The authors studied 1,100 patients with localised cancer (T1c-T3) and divided them into three prognostic risk groups according to pre-treatment variables. If pre-treatment PSA was less than 10, stages T1-2 and Gleason of 6 or greater, the patients prognosis was considered favourable. If 1 of these values was increased they were intermediate and if 2 values were increased they were classified in the unfavourable group. 3D conformal therapy was administered in 810 patients 64.8 to 75.6 Gy was given (the initial 61 received 81 Gy) and 229 received 81 and 86.4 Gy intensity modulated therapy. Their results, in terms of PSA relapse-free survival rate for the favourable group, were 85%, for the intermediate group 58% and for the unfavourable group 38%. The radiation dose was the most powerful variable to have an impact on PSA relapse-free survival in each prognostic group. For example, in the favourable group, the PSA relapse-free survival was 90% in those treated with 75.6 to 86.4 Gy, compared with 77% for those in the same group treated with 64.8 to 70.2 Gy. The incidence of toxicity was found to be dose-related with 3D conformal therapy. At 5 years (with 3D conformal therapy) the rate of rectal toxicity was 14% (with 75.6 Gy or greater) compared to 5% (in those treated at a lower level). They reported that the incidence of rectal toxicity was significantly decreased in those treated with intensity modulated radiotherapy, compared with those treated with 3D conformal therapy. In conclusion, they stated that these sophisticated radiotherapy techniques offered improved biochemical outcome to those with localised prostate cancer, and that this technique is associated with decreased local toxicity. This data is, at first glance, very powerful, although it is weakened by their definition of PSA failure, which is defined as 3 successive PSA elevations after achieving a post-treatment nadir. This therefore makes their outcome sensitive to the duration of follow up. This is particularly important in those prognostic groups who may not experience a third relapse until 3 or 4 years after treatment. Therefore, if their follow up is not "long enough," their PSA failure will not be recorded.

Reviewer: Jon-Paul Meyer

Journal:	Cancer
Authors:	Coffey RNT, Watson RWG, Hegarty PK, Watson CL, Wolohan L, Brady HR, O’Keane C, Fitzpatrick JM.	Issue:	2001, 92: 2297-2308

Title:

Priming prostate carcinoma cells for increased apoptosis is associated with up-regulation of the caspases

Abstract:
This paper explores the possibility of priming prostate cancer cell lines for apoptosis. It has previously been demonstrated that cell lines, pre-treated with diethyl-maleate, (DEM) are increasingly susceptible to apoptosis prior to the induction of the process of apoptosis by the Fas antibody, cycloheximide, etoposide and radiation. Despite this, the underlying mechanisms are not fully known. In this study the authors evaluated the effects of DEM on both protein and RNA expression using Western blot analysis and a ribonuclease protection assay. They found that DEM did not affect the expression of the caspases at the transcriptional level but it was associated with increased procaspase-3 and caspase-8 protein levels. Also demonstrated was the fact that pre incubation of DEM restored sensitivity to the Fas antibody and radiation induced apoptosis in cells from the LNCaP bcl-2 cell line which are normally resistant to these apoptotic stimuli. This research provides a potential target, ie the caspases, for chemical manipulation in the treatment of prostate cancer. They may serve as an effective approach in strategies that rely on the activation of these death effector proteases.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Recker F, Kwiatkowski K, Huber A, Stamm B, Lehmann K and Tscholl R	Issue:	2001, 166: 851-855

Title:

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng/ml combined with free to total ratio 20% or less: The Aarau experience

Abstract:
In this paper the authors prospectively examined the incidence and clinical relevance of prostate cancer in men with PSAs in the range 1-3 with free-to-total ratios of less than 0.20. They recruited 168 men for this study, with the patients being taken from the Aarau, Switzerland, section of the European Randomised Study of Screening for Prostate Cancer. Out of the 168 men, 158 underwent prostatic biopsy, and prostate cancer was detected in 17 men (10.8%). Of these 17 men, 14 underwent surgery. There was no statistical difference between prostate cancer and benign prostatic hyperplasia with regard to patient age, prostatic volume, PSA, free-to-total-ratio, PSA density, or PSA transition zone density. In those with prostate cancer, the median Gleason score on biopsy was 5, whereas the median Gleason score was 6 on retropubic prostatectomy specimen. In the 14 who underwent radical surgery, there were positive lymph nodes in 1, stage pT3b Gleason & disease in 1, organ confined disease in 2 (Gleason 5), Gleason 6 in 5 and Gleason 7 in 5. In conclusion, the authors felt that there were a significant number of cancers being detected in those with PSAs of between 1 and 3. These findings certainly need verifying in a larger cohort of patients and if correct, certainly give food for thought in relation to performing a prostatic biopsy in those with PSAs of less than 3.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Yao S.L, Lu-Yao	Issue:	2001, 166: 861-865

Title:

Interval after prostate specific antigen testing and subsequent risk of incurable prostate cancer.

Abstract:
In this study the authors examined the relationship of less frequent PSA testing and the risk of non-localised incurable cancer. They also studied the effect of testing frequency on the risk of prostate biopsy in men who were ultimately diagnosed with prostate cancer. Their study population was 36,422 men, 65 years of age or older, each with newly diagnosed prostate cancer. Their primary endpoint was the risk of non-localised cancer, as determined by logistic regression. As covariates, the authors included age, geographic region, year of diagnosis and race. They found that the risk of non localised prostate cancer in those who would be diagnosed with prostate cancer did not differ significantly between those tested every 2 to 3 years and those tested a year prior to diagnosis. However, they reported that the risk of prostatic biopsy in these men was directly related to the number of PSA tests performed. The authors conclude that patients receiving PSA testing could undergo biennial testing rather than annual testing. This would represent an economic boost, as PSA testing costs could be effectively halved. Also, the quality of life of screened patients may be optimised, with less frequent PSA testing.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Borboroglu P.G, Sur R.L, Roberts J.L, Amling C.L	Issue:	2001, 166: 866-870

Title:

Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy

Abstract:
In this paper the authors report their results of repeat biopsy in those with high grade prostatic intraepithelial neoplasia (PIN) and/or small acinar proliferation. Their figures reveal that, of the 1,391 men biopsied, 137 (9.8%) had high grade PIN or atypical small acinar proliferation; 100 of these patients underwent repeat prostatic biopsy. Adenocarcinoma was detected in 47 of these 100 patients. In 22 cases (47%) the area of cancer in the prostate matched with the initial area of PIN or atypical small acinar proliferation. Therefore they stated that, if repeat biopsy was only directed to the initial area of PIN or atypical small acinar proliferation, then 53% of cancers would have been missed. In 12 of the 47 men (26%) cancer was limited to the side of the prostate contralateral to the side of high grade PIN or atypical small acinar proliferation. 31 patients had the transitional zone sampled and, in 4 (13%), cancer was limited to this region alone and, cancer was noted to be evident at other sites in 13 (42%). This study, albeit using a small group of only 100 men, suggests that all those with high grade PIN should be offered a second biopsy, especially as this study reports a 47% incidence of cancer on second biopsy. Also, if the repeat biopsies were taken of the initial abnormal areas, only 47% of the cancers would have been detected. Therefore it would seem appropriate to perform a standard sextant bilateral biopsy of the prostate gland.

Reviewer: Jon-Paul Meyer

Journal:	Urology
Authors:	Soulie M, Seguin P, Benoit JM, Escourrou G, Tollon C, Vazzoler N, Pontonnier F, Plante P.	Issue:	2001; 58 (2): 217-221.

Title:

Impact of a modified apical dissection during radical retropubic prostatectomy on the occurrence of positive surgical margins: a comparative study in 212 patients.

Abstract:
The authors present a series of 212 patients which assesses the impact of using a modified technique for the apical dissection during a radical retropubic prostatectomy (RRP) on the occurrence of positive surgical margins (PSM). During a 6 year period 212 patients with either T1 or T2 localized prostate cancer underwent RRP. Patients having surgery in the first 2 years were assigned to group 1 (85 men) and in the last 4 years assigned to group 2 (127 men). Group 2 patients underwent a modified technique of apical dissection consisting of a wide excision of periprostatic tissue at the apex, which included the neurovascular bundles bilaterally. The authors then compared the PSA, clinical stage, pathological stage, Gleason score and PSM rate between the groups. They reported no significant difference between the two groups in terms of PSA, Gleason score and pathological staging. However, the PSM rate was different between the two groups, with a PSM rate of 53% in group 1 and 20.5% in group 2. The authors concluded reporting that using this modified technique of apical dissection the PSM rate is significantly reduced. It could be argued that this difference exists, because in the first 2 years there was an element of a learning curve developing, giving an initial higher PSM rate. Also, these are results from 2 surgeons rather than a single surgeon. Despite this, the results here are promising and a further study looking at a larger series of patients should be considered.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Boomsma JHB, Groenier K, Piers DA, Mensink HJA	Issue:	2001; 88: 226-230

Title:

Routine bone scans in patients with prostate cancer related to serum prostate specific antigen and alkaline phosphatase

Abstract:
In this paper the authors evaluate the need to perform bone scan routinely on patients diagnosed with prostate cancer. They evaluated this need in relation to the prostate specific antigen (PSA) and the alkaline phosphatase (ALP) levels. They looked retrospectively at 363 patients with newly diagnosed prostate cancer. They found that of these 363 patients 111 had a positive bone scan. 144 patients with a PSA of <20 had bone scans and it was reported that 19 of them were positive, they termed this group of 19 patients as ‘missed diagnosis’. They used the term ‘false positive’ to describe the group of 125 patients with a PSA of >20 and with a negative bone scan. The authors felt that a "cut off" level of ALP of 100 provided a better balance for the number of ‘false positives’ and ‘missed diagnosis’. They reported that ALP values rather than PSA readings correlated better with bone scan findings (although not significantly so). In conclusion, they reported that they felt that a patient with a newly diagnosed case of prostate cancer should have a bone scan if their ALP is >90, or if they suffer with pain of boney origin. This is an interesting study as the debate as to whether patients should have bone scans routinely has waged for a considerable time, with recent reports discouraging the use of routine bone scans in men with a PSA of <20. However, this study suggests that there is a greater chance of men with PSAs of <20 having a positive bone scan than other studies suggest. In order to confirm or refute these beliefs a prospective rather than a retrospective study needs to be conducted.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Wymenga LFA, Groenier K, Schuurman J, Boomsma JHB, Elferink R, Mensink HJA	Issue:	2001; 88:231-5

Title:

Pre-treatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis.

Abstract:
This is a retrospective study designed to assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD) as indicators of bone turnover in patients with prostate cancer. The authors assessed urinary DPD, serum ALP and PSA in 23 patients with benign prostatic hypertrophy (BPH), 115 with prostate cancer, 21 of whom had bone metastasis, and also in 16 age-matched controls. The results reported revealed that in patients with prostate cancer and bone metastasis higher levels of urinary DPD and higher levels of PSA and ALP were recorded when compared to patients with BPH and patients with prostate cancer without bone metastasis. The authors therefore concluded that urinary DPD and serum ALP are the best predictors of bone metastasis in men with prostatic carcinoma. In order to verify this a larger study group is required, although a combination of serum ALP and PSA along with urinary DPD, could help determine who has bone metastasis and therefore who should have a bone scan.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Jeffrey M. Carey, Howard J. Korman	Issue:	2001; 166: 82-85.

Title:

Transrectal ultrasound guided biopsy of the prostate. Do enemas decrease clinically significant complications?

Abstract:
This retrospective review attempts to assess the role of bowel preparation with an enema before transrectal ultrasound (TRUS) guided biopsy of the prostate, and it’s effects on complications of the procedure. Two cohorts of demographically similar patients (including identical antibiotic prophylaxis) were compared, the only variable being the use of an enema before biopsy. The study involved a retrospective review of a total of 448 TRUS biopsies performed by 3 urologists, two of whom used Sodium biphosphate enemas 4 hours before the procedure, and one of whom did not. Of the 448 patients, 38 were excluded due to the use of alternate antibiotics. Of the remaining 410 patients, 225 received enemas before biopsy, while 185 did not. Patient variables - age, serum PSA, co-morbidity were assessed as were biopsy parameters - number of core samples, presence/absence of prostatitis or adenocarcinoma on the pathology report. All patients were counseled before the procedure on the antibiotic prophylaxis and possible complications, and were instructed to contact the office should any complications arise. Patients were also questioned about complications when informed of the biopsy reports. Clinically significant complications included urinary tract infections, secondary clinic visit, treatment, procedure or hospitalisation. Complications occurring after 30 days were excluded. A total of 10 patients (4.4%) developed clinically significant complications in the enema group, while 6 (3.2%) of the patients who did not receive an enema had complications. There were no significant differences in the variables between the two groups, nor was there a significant difference between the diagnosis. Although the rate of complications was statistically significant in each of the two groups, there was no statistically significant difference between the two groups, concluding that the use of an enema before TRUS biopsy confers no clinical advantage. TRUS biopsy accompanied by antibiotic prophylaxis remains a relatively safe procedure. Two possible criticisms of this study are it’s retrospective design and that the two groups of patients were biopsied by different urologists. The latter may be a possible cause of some bias.

Reviewer: Biral Patel

Journal:	BJU International
Authors:	L.Mucci, R. Tamimi, P.Lagiou, A.Trichopolou, V.Benetou, E.Spanos, D. Trichopolous	Issue:	2001, 87:814-20

Title:

Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?

Abstract:
The strange thing about this paper is that, although its title mentions prostate cancer, the disease appears incidental to the trial; indeed, there is no mention of any attempts to establish a diagnosis in any of the subjects. The paper therefore describes a study that has little to do with prostate cancer and is essentially a correlation of an epidemiological assessment of dietary intake with levels of IGF-1 and its binding protein, IGFBP-3. The authors have then linked this to prostate cancer risk on the basis of previously published studies linking IGF-1 levels with prostate cancer risk. One wonders whether the same data has been used in other papers discussing the risk of other cancers known to be linked to IGF levels. The subjects are 112 patients admitted to Greek teaching hospitals for non-cancer diagnoses, who were questioned about dietary intake and this was then correlated with serum IGF-1 & IGFBP-3 levels. Most of the patients are over 65 years of age and thus in a high-risk group for prostate cancer. It is strange therefore that the authors did not even perform a serum PSA assay by way of excluding prostate cancer. It is also questionable whether dietary patterns at this age are likely to have any effect on prostatic carcinogenesis (as the authors mention, IGF levels fall with rising age). The major finding was that intake of cooked tomatoes correlates inversely with serum IGF-1 level, as does alcohol to a lesser extent. Before all urologists start recommending high doses of ‘Bloody Marys’ to their middle-aged male patients, it is worth noting that, as mentioned above, no evidence of any link to prostate cancer has been shown in the study. Serum IGF-1 has been used as a surrogate end-point for prostate cancer risk which constitutes a major flaw in the study.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	J.Peters, A.Thompson, T.McNicholas, J.Hines, D.Hanbury, G.Boustead	Issue:	2001, 87:827-30

Title:

Increased patient satisfaction from transrectal ultrasonography and biopsy under sedation

Abstract:
There is increasing interest in the patient experience associated with transrectal prostatic biopsy and this is one of many papers which have examined the role of anaesthesia or sedation for this procedure. The design of the study is rather strange in that it includes both retrospective and prospective elements. Strangely, the prospective part was not randomised and patients were allocated according to an anaesthetist's assessment of their suitability for sedation. This is unfortunate because it is an obvious potential source of bias; clearly the study personnel had assumed that sedation was desirable prior to the trial. As might be expected, patient discomfort was less with sedation and overall satisfaction was also improved. Assessment was made using visual analogue scores performed at least two weeks after the procedure. There were no complications relating directly to the sedation. One feature that the authors have overlooked is the quality of biopsy specimens obtained. I remain to be convinced that converting a moderately unpleasant outpatient procedure to a day case procedure requiring anaesthetic support is progress. If the authors had shown better sampling and a smaller requirement for repeat biopsies, this would have been a useful addition. Overall, this trial is let down by its poor design and limited parameters. A properly controlled randomised trial would have been more informative.

Reviewer: Kieran Jefferson

Journal:	Lancet
Authors:	F.Frauscher, A.Klauser, E.Halpern, W.Horninger, G. Bartsch	Issue:	2001, 357: 1849-50

Title:

Detection of prostate cancer with a microbubble ultrasound contrast agent

Abstract:
The high incidence of negative TRUSS-guided biopsy specimens in suspected prostate cancer warrants a search for better prostate imaging, to both improve the chance of hitting a cancer with the biopsy needle and to reduce the need for biopsy in normal prostates. This paper describes the use of an intravenous microbubble ultrasound contrast agent (which resonates at the ultrasound frequencies used and therefore highlights areas of increased vascularity, such as tumours) to improve prostatic tumour imaging and biopsy. Ninety asymptomatic volunteers participating in a screening trial were recruited, of whom 84 were evaluable. All patients had a microbubble contrast enhanced colour Doppler scan with targeted biopsies (5 or fewer) prior to a standard grey scale ultrasound scan with non-targeted systematic biopsies (10). Twenty-four patients had prostate cancer, of whom 23 were detected using the contrast enhanced targeted biopsy technique, compared with 17 using the conventional systematic biopsy technique. The probability of each core containing cancer tissue was increased by a factor of three. Cancers detected using the contrast technique were of moderate to high Gleason grade. This study suggests that contrast enhancement of transrectal ultrasound could considerably improve targeting of biopsy specimens, both improving detection and reducing pathology costs and possibly patient morbidity associated with TRUSS-guided biopsy.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Chang S, Reuter V, Heston DW, Gaudin PB	Issue:	2001: 57:1179-1183

Title:

Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma

Abstract:
Prostate specific membrane antigen (PSMA) is expressed in all types of primary prostatic tissue. Prostate cancer PSMA expression has made PSMA an attractive diagnostic target. Indium 111 labelled 7E11 conjugate is used as a radiodiagnostic marker for prostate cancer. In this paper the authors set out to compare the immunohistochemical properties of the 7E11 anti prostate specific membrane antigen (anti PSMA) monoclonal antibody (mAb) with the anti PSMA mAb, PM2J004.5. They examined 23 formalin fixed specimens of metastatic prostate cancer from various sites. They performed immunohistochemical reactions with anti PSMA mAbs 7E11 and PM2J004.5 and with antibodies to prostate specific antigen and prostatic acid phosphatase. The reactions being scored by pathologists blinded to the clinical and pathological data on the specimens. They found that anti-PSMA mAbs consistently immunoreacted with metastatic prostate cancer specimens and were positive when prostate specific antigen staining was negative. The anti PSMA mAbs revealed similar patterns but in some cases the PM2J004.5 mAb did show more intense staining. The authors concluded that the anti PSMA mAbs 7E11 and PM2J004.5 are useful in the pathological evaluation of metastatic prostate cancer specimens, although clearly a larger study is required.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Solsona E, Iborra I, Rubio J, Casanova JL, Ricos JV, Calabuig C.	Issue:	2001, 165: 1506-9

Title:

Prospective validation of the association of local tumour stage and grade as a predictive factor for occult lymph node micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes

Abstract:
This paper is of great interest, despite its cumbersome title. It follows on from a paper published by the same group in 1992, describing how tumour stage and grade was a reliable predictor of occult lymph nodal involvement in a retrospective series of 66 patients treated over a 28 year period. The authors are to be commended for subjecting their recommendations from the first study to prospective analysis in a further 37 patients over an 8 year period. This new study confirms the findings of their original study; i.e. prophylactic lymphadenectomy is essential for patients with high stage and grade primary tumours of whom 83.3% had micrometastases, but unnecessary in patients with low stage and grade disease. Unfortunately, around a third of the patients fall into an intermediate group, for whom the decision to operate or not remains unclear. Patients were followed up for a minimum of 36 months. As the authors state, further predictive markers are needed for the intermediate group, however one can provide clear advice to patients with either high or low risk disease on the basis of this study, which is relatively large for this uncommon disease.

Reviewer: Kieran Jefferson

Journal:	International Journal of Cancer
Authors:	Lacombe L, Maillette A, Meyer F, Veilleux C, Moore L, Fradet Y.	Issue:	2001, 95: 135-9

Title:

Expression of p21 predicts PSA failure in locally advanced prostate cancer treated by prostatectomy

Abstract:
One of the dilemmas of selecting patients for radical prostatectomy is trying to predict those who will develop biochemical failure. Clinicopathological criteria such as Gleason score, lymph node metastases and seminal vesicle involvement exist which help to do this. This paper investigates another potential prognostic indicator by studying the expression of a protein - p21, in patients who had undergone RRP and were subsequently found to have pT3 tumors, and correlated it to several clinicopathological features and PSA failure. The p21 WAF1/ CIP1 gene is regulated by p53 and may be involved in arresting the cell cycle. A prospective cohort of 296 patients provided the tissue samples to which the specific monoclonal antibody to p21 WAF1/CIP1 was added. 124 of them received neoadjuvant hormone therapy and all cases were adenocarcinoma of the prostate. The pattern of p21 over-expression was determined using standard immunohistochemical techniques. The results showed no statistical difference in p21 over-expression for any of the clinicopathological variables analyzed. Similarly, for the entire group, there was a higher rate of PSA failure in those with p21 positive tumors (i.e. > 5% of tumor cell nuclei staining for p21) although the difference was not significant. However, in the 172 patients who only had RRP, p21 positive tumors had a higher rate of PSA failure, which was statistically significant (p=0.01). In most cancers, except for prostate and hepatocellular carcinoma, a negative p21 expression is associated with a poor prognosis. In the few reports on prostate cancer, the results were somewhat contradictory. In series, it is possible that p21 over-expression is compensating for other defective inhibitory pathways of the cell cycle which would explain its association with a poorer outcome. Alternatively, p21 positivity may be due to its sequestration in an inactive form or a normal response to an increase in proliferation stimuli. The authors thus conclude that in patients with pT3 tumors treated by RRP alone, p21 over-expression appears to be an independent predictor of PSA failure and may be useful in identifying those who will require adjuvant therapy.

Reviewer: Marto Sugiono

Journal:	Urological Oncology
Authors:	Arnold PM, Niemann TH, Bahnson RR	Issue:	2001; 6:91-93

Title:

Extended sector biopsy for detection of carcinoma of the prostate.

Abstract:
This paper examines whether an extended sector biopsy of the prostate increases the detection of prostate cancer. The authors performed a transrectal ultrasound and biopsy on 74 men with either an elevated PSA or abnormal digital rectal examination. A single operator performed the biopsies, taking 12 samples in total, a normal sextant biopsy, 2 from each of the peripheral zones and 2 from the transitional zone. Of the 74 men, 40 (54.1%) were positive for adenocarcinoma of the prostate, with 10 of these 40 (25%) cancers being detected in the additional zones only, or 13.5% of all patients biopsied. In these 74 men there was 1 complication (1.4%) of urinary retention and fever. The results from this study suggest that taking an extended sector biopsy may increase the detection of prostate cancer with respect to the normal sextant biopsy, without any significant rise in patient morbidity. To verify these finding a larger study should be performed.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Boyle BJ, Zhao XY, Cohen P, Feldman D	Issue:	2001, 165: 1319-24

Title:

Insulin-like growth factor binding protein 3 mediates 1a,25-dihydroxyvitamin D3 growth inhibition in the LNCaP prostate cancer cell line through p21/waf1

Abstract:
This paper potentially provides some insight into the mechanism of vitamin D mediated anticancer effects in the prostate. The same group has previously shown that high doses of IGFBP3 can induce apoptosis in prostate cancer cells, which may explain the epidemiological association between high IGFBP3 levels and reduced risk of prostate cancer. 1,25OH-D3 inhibited cellular proliferation in the LNCaP cell line and elevated levels of IGFBP-3 in the culture medium. The authors tested the hypothesis that IGFBP-3 had a causal role in this inhibition by the use of blocking polyclonal antibodies to IGFBP-3 and antisense oligonucleotides to decrease IGFBP-3 mRNA synthesis. Exogenous IGFBP-3 had similar effects. The authors went on to show that both 1,25OH-D3 and IGFBP-3 up-regulated expression of p21/waf1, a cyclin-dependent kinase inhibitor, and postulated that this was the mechanism of their effects. There are two potential concerns about this paper. Firstly, the experimental culture conditions are unusual in that the medium used for the experiment is different to that used to grow the cells. The authors comment upon this and appear to imply that these effects are not seen using other media, which must lead one to question their significance. Also, a general urological journal would not be the obvious place to publish such work, suggesting that a cell science journal may not have had confidence in the findings.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Power DA, Brown RS, Brock CS, Payne HA, Majeed A, Babb P	Issue:	2001, 87: 361-365

Title:

Trends in testicular carcinoma in England & Wales 1971-1999

Abstract:
This paper uses a database held by the National Cancer Intelligence Centre to analyse trends in the incidence of testicular cancer and its treatment. Incidence data were available for 1971-1997, as were mortality data for 1971-1999. Annual and age-standardised incidence and mortality rates were calculated, and the effect of social status on incidence and survival was also assessed. The incidence of testicular tumours almost doubled over the period studied, but mean age at diagnosis remained static at 36 years. Seminomas were more common than teratomas. Mortality, however, has fallen by a factor of 3 despite the increased incidence, which appears directly attributable to the introduction of platinum-based chemotherapeutics in the late 1970s. The most recent year assessable had a 1-year survival of 98% and 5-year survival of 95%. Interestingly, social class has a significant effect on survival with those in the lowest socioeconomic group, having about a 6% smaller chance of surviving 5 years. The reasons for this are uncertain, but the authors propose that social factors may affect presentation and compliance with treatment.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Moody J, Lingeman J	Issue:	2001, 165:459-62

Title:

Holmium laser enucleation for prostate adenoma greater than 100gm.: comparison to open prostatectomy

Abstract:
This paper attempts to compare holmium laser prostate enucleation with open prostatectomy in a small number of patiebts in a single institution with very large prostates. It is a retrospective unrandomised analysis of ten patients in each group with comparison of a number of patient, operative and post-operative parameters. To a large extent the paper confirms the safety of holmium laser enucleation in these patients although a significant number of short-term complications were seen. Unfortunately the work is entirely retrospective and does not address the main question about such novel BPH treatment technologies. It seems unlikely that any institution could justify the expense of such a system for the small number of patients with very large prostates, therefore the real issue is how holmium laser enucleation compares with standard TURP for the bulk of BPH patients. Hopefully the authors of this paper are in the process of conducting a prospective randomised controlled trial to confirm the potential of the holmium laser.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Kamai T, Arai K, Tsujii T, Honda M and Yoshida K.	Issue:	2001, 87: 227-31

Title:

Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour

Abstract:
In this paper the authors aim to clarify the role of the Rho small GTP binding protein in the progression of testicular germ cell tumour (GCT). The Rho subfamily (RhoA, RhoB and RhoC) regulates the formation of stress fibres and focal adhesions in cells, and is known to be overexpressed in breast, colon and lung cancer. Observations in these tumours suggest that Rho may be associated with carcinogenesis, progression and metastasis in human tumours. To ascertain its involvement in testicular GCT the authors studied specimens of testicular GCT tissues from 45 Japanese patients. The mRNA levels of Rho A, B and C were analysed in the surgical specimens of testicular GCT tissues, and in the corresponding unaffected tissue originating from the same patient. A reverse transcription-polymerase chain reaction was used. They compared the expression levels in tumour tissue with non-tumour tissue, and expression levels between seminomas and tumours with mixed seminoma and nonseminoma components. Interestingly, they found that the levels of RhoA were higher in tumour tissue than non tumour tissue, and that the increase in RhoA was related to tumour stage. RhoB and C were not detected in either tissue. It was reported that RhoA levels were higher in tumours with seminomatous and nonseminomatous components than in tumours with seminoma only. The authors felt that the results suggested that RhoA is involved in testicular germinal epithelial carcinogenesis and progression in testicular GCT. As a result of this study RhoA may turn out to be a useful prognostic marker for progression in testicular GCT. As a follow on from this study, the authors plan to investigate the relationship between mRNA levels of Rho genes and prognosis.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Lance RS, Freidrichs PA, Kane CR, Powell CR, Pulos JW, Moul JW, Mcleod DG, Cornum RL and Thrasher JB	Issue:	2001, 87: 61 - 5

Title:

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group

Abstract:
This paper describes a retrospective review of 1382 men who were treated by radical retropubic prostatectomy (RRP) and 316 men treated by radical perineal prostatectomy (RPP). The authors assessed the following variables; age, race, prostate specific antigen (PSA) level before surgery, clinical stage, biopsy Gleason sum, estimated blood loss (EBL) which was defined as the volume of blood loss during surgery as recorded by the anaesthetist, margin positive rate, pathological stage, biochemical recurrence rate, short and long term complication rates, impotence and incontinence rates. The aims of this study were to compare the outcomes of those undergoing the ‘gold standard’ RRP group with the RPP group. The men were identified using the Uniformed Services database, with patients being drawn from San Diego, Washington and San Antonio. The authors used pairs of patients from the two groups matched by race, preoperative PSA level, clinical stage and biopsy Gleason sum to provide ‘the most accurate comparison’ between the two groups. 190 matched patients were studied. The results showed that there were no significant differences between the RRP and RPP groups in either organ-confined (57% vs 55%), margin positive (39% vs 43%), or biochemical recurrence rates (12.9% vs 17.6%) at a mean follow up of 47.1 vs 42.9 months respectively. The mean EBL was 1575mls in the RRP group and 802mls in the RPP group (P<0.001). The authors recorded a significant difference in complication rates in that there was a higher incidence of rectal injury in the RPP group (4.9%) than in the RRP group (none, P<0.05). This aside the morbidity rates were not significantly different between the two groups. The reported results would suggest that RPP compares favourably with the ‘gold standard’ RRP. Potential weaknesses of this study are that, their results for a decreased EBL could be open to question given that this figure was assessed by different anaesthetists in different centres therefore introducing intraobserver variations, and that relatively short follow up times were used to assess biochemical recurrence. Ultimately, a longer follow up period is required to compare cancer control rates in the patients undergoing RPP, to see how it compares to the ‘gold standard’ RRP.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Ouyang RC, Kenwright DN, Nacey JN and Delahunt B	Issue:	2001, 87: 70 - 4

Title:

The presence of atypical small acinar proliferation in prostate needle biopsy is predictive of carcinoma on subsequent biopsy.

Abstract:
Most prostatic biopsies that are taken are readily diagnosed as benign or malignant, although a small proportion are reported as containing atypical features. To differentiate between atypical and benign or malignant biopsies the term ‘atypical small acinar proliferation’ (ASAP) has been introduced. This paper sets out to determine the significance of finding ASAP in prostatic biopsies with clinical findings suggestive of malignancy. The authors looked at 331 patients who underwent prostatic biopsies over a period of 30 months. Of this number 21 (6.3%) had atypical features histologically and, out of these, 17 underwent a second biopsy. A further group of 20 patients with normal histology also underwent a repeat biopsy for persistent abnormal clinical findings. The clinical features of patients who were diagnosed with carcinoma after an initial atypical biopsy were compared with those who had a second biopsy on clinical grounds. The variables recorded by the authors were age, initial PSA level and the mean interval between first and second biopsy. In the biopsies diagnosing carcinoma, the Gleason pattern was compared between the 2 groups. They reported that 9 patients with atypical histology and 4 patients with normal histology initially, were found to have carcinoma on subsequent biopsy. They found that the Gleason pattern was not significantly different between the 2 groups and that the measured variables did not differ between those with atypical features and those with normal histology initially. They reported that only the PSA level varied significantly in patients with normal or malignant repeat biopsy in the group with an initial normal biopsy. The authors felt that the presence of atypical features on prostatic biopsy is a strong indication for repeat biopsy. Of interest, they reported that, in 7 of the 9 patients who were subsequently found to have carcinoma, the areas of malignancy were in different sites to the initial sites of the atypical features. This they felt strengthened the view that on finding atypical features the whole gland should be sampled and not just the area of atypia. In conclusion, the authors felt that the presence of atypical features on prostatic biopsy is a strong predictor of underlying malignancy requiring follow up investigation. Despite the small numbers involved in this study, this would appear to be a very valid conclusion and would certainly warrant a further study with larger numbers of patients.

Reviewer: Jon-Paul Meyer

Journal:	Nature Medicine
Authors:	DeFeo-Jones D, Garsky VM, Wong BK, Feng DM, Bolyar T, Haskell K, Kiefer DM, Leander K, McAvoy E, Lumma P, Wai J, Senderak ET, Motzel SL, Keenan K, Zwieten MV, Lin JH, Freidinger R, Huff J, Oliff A and Jones RE	Issue:	2000, 6: 1248-1252

Title:

A peptide-doxorubicin ‘prodrug’ activated by prostate-specific antigen selectively kills prostate tumor cells positive for prostate specific antigen in vivo.

Abstract:
This paper describes initial results of using a peptide-doxorubucin conjugate to act as a prodrug, which is activated by the serine protease activity of PSA. Since most plasma PSA is either conjugated with plasma proteins or inactivated by circulating inhibitor proteins, the prodrug releases doxorubicin only close to PSA-bearing tissue. It therefore provides a useful means of targetting doxorubicin to malignant prostatic tissue. The authors have used this molecule in both cell culture and animal models of prostate cancer and show effective tumour cell killing with low systemic toxicity. Control arms involving unconjugated doxorubicin and a non-PSA susceptible peptide conjugate showed a considerably reduced therapeutic ratio. Such conjugates offer great potential as ‘magic bullets’ to reduce the systemic toxicity of chemotherapeutic regimens and improve local tumour toxicity. Clinical studies will be awaited with interest.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Shariat SF, Bergamaschi F, Adler HL, Nguyen C, Kattan MW, Wheeler TM and Slawin KM	Issue:	2000, 56(3): 423-429

Title:

Correlation of preoperative plasma IGF-1 levels with pathological parameters and progression in patients undergoing radical prostatectomy.

Abstract:
This paper investigates whether serum IGF-1 levels can be used to predict stage and grade prior to radical prostatectomy and/or disease recurrence or progression. The authors measured IGF-1 levels in preoperative plasma samples and rigorously followed patients post-operatively with regular biochemical and clinical evaluations, notably PSA. Plasma IGF-1 levels have been shown to be an independent and strong risk factor for prostate cancer in middle aged male populations. At a median follow-up of four years, preoperative IGF1 levels did not correlate with prostatic malignancy when compared to normals, with stage or grade of prostatic malignancy nor with prognosis. These results are perhaps not surprising given the nature of IGF physiology; most circulating IGF is complexed and this limits exchange between the circulating and tissue compartments. Furthermore, there is a high circulating level synthesised by the liver and any leak back into the circulation from the tissues might be expected to have little effect on the overall plasma level. These results, however do not rule out a role for IGFs in prostate cancer pathogenesis and progression. In addition to epidemiological data reporting the link between IGF levels and cancer risk, there is direct evidence from a number of experimental systems of paracrine and autocrine IGF effects. In order to gauge these effects, more subtle assays than plasma IGF1 level will be required.

Reviewer: Kieran Jefferson

Journal:	Journal of the American Medical Association
Authors:	Fowler FJ Jr, McNaughton Collins M, Albertsen PC, Zietman A, Elliott DB and Barry MJ	Issue:	2000, 283: 3217-3222

Title:

Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localised prostate cancer.

Abstract:
This paper describes the results of a postal survey examining therapeutic recommendations coming from different specialists. The authors sent out a large mailshot to physicians registered as urologists or radiation oncologists with the AUA and received a good proportion of replies (64% of urologists and 76% of radiation oncologists). They analysed data from these cohorts of 504 urologists and 559 radiation oncologists. The questionnaire differed between the two specialties and unfortunately no examples are given as appendices to the paper. The urologists’ questionnaire apparently also included questions about prostatitis and benign prostatic hypertrophy but this data is not discussed. Urologists promoted PSA testing to a younger group of patients and felt testing to be worthless at an earlier age than oncologists. As might be expected, the vast majority of respondents felt that benefit from radical prostatectomy, external beam radiation or brachytherapy was limited to patients with a greater than 10-year life expectancy and tended to believe more in the efficacy of the treatments that they actually performed. The striking differences were in the perceived effectiveness of radical prostatectomy and external beam radiotherapy in organ confined, moderately differentiated tumours in younger men. Here, urologists were much more likely to predict advantage for RP over radiotherapy. The paper is interesting, but a poor substitute for what all doctors treating prostate cancer need, i.e. definitive data comparing treatment regimens with long-term follow-up. I suspect its content will come as little surprise to doctors with a prostate cancer practice.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Tiguert R, Gheiler EL, Grignon DJ, Littrup PJ, Sakr W, Pontes JE and Wood DP	Issue:	2000, 163:1486-1490

Title:

Patients with abnormal ultrasound of the prostate but normal digital rectal examination should be classified as having clinical stage T2 tumors.

Abstract:
Prostate tumours with abnormal transrectal ultrasound but normal digital rectal examination are currently classified as clinical stage T2. However, most urologists consider these tumors as clinical stage T1c due to the perceived inaccuracy of transrectal ultrasound in clinical staging. This group examined the role of transrectal ultrasound in the clinical staging of prostate cancer. They evaluated the pathological stage and disease-free survival of patients undergoing radical prostatectomy who had tumour detected by needle biopsy because of elevated serum prostate specific antigen with or without transrectal ultrasound abnormalities. Between 1991 and 1996, 738 patients underwent radical retropubic prostatectomy as monotherapy for clinically localised prostate cancer. Patients with normal digital rectal examination and transrectal ultrasound had a better disease-free survival compared to patients with normal digital rectal examination but abnormal transrectal ultrasound and patients with abnormal digital rectal examination (p = 0.003 and p = 0.002, respectively). There was no difference in disease-free survival between the later two groups (p = 0.39). This supports the use of transrectal ultrasound findings in the clinical staging system for prostate cancer. Patients with normal digital rectal examination, elevated serum prostate specific antigen and abnormal transrectal ultrasound should be considered as having clinical stage T2 disease.

Reviewer: Matthias Winkler

Journal:	BJU International
Authors:	Brossner C, Bayer G, Madersbacher S, Kuber W, Klingler C and Pycha A	Issue:	2000, 85: 705-7

Title:

Twelve prostate biopsies detect significant cancer volumes (> 0.5 ml).

Abstract:
Extended field biopsy of the prostate (incorporating far lateral peripheral zone biopsies) has been shown to increase cancer detection rate by up to 20%. It is not clear whether this increases the pick up rate of insignificant tumours that do not require radical treatment. In a retrospective study, pathological specimens of prostate cancer detected in additional areas of a 12-core biopsy were compared with tumours detected using traditional sextant biopsy. The study included 27 patients who had undergone radical prostatectomy (RP) for prostate cancer. Of the 27 patients, six (29%) had cancer detected in the extra six biopsy cores which would otherwise have been undetected using sextant biopsy. Only two insignificant cancers were detected. The mean Gleason score was 6.1 for cancer detected by the sextant or 12-core method (p = 0.907). The mean (median, range) tumour volume was 5.7 (3.5, 0.312-23.75) mL for cancers detected on sextant biopsy and 1.99 (1. 85, 0.4-3.6) mL in the six cancers detected using extra cores (p = 0. 0138). As shown in prospective studies the detection of prostate cancer was increased using extra biopsy cores. Although there was a significant difference in tumour volume, Gleason score and final pathological tumour stage were similar between tumours diagnosed using 12 cores and those detected on sextant biopsy.

Reviewer: Matthias Winkler

Journal:	Am. J. Surg. Pathol.
Authors:	Pan CC, Potter SR, Partin AW and Epstein JI	Issue:	2000, 24: 563-569

Title:

The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system.

Abstract:
The Gleason grading system of prostatic adenocarcinoma does not account for the existence of a tertiary (third most prevalent) pattern, and the authors hypothesise that the latter may have prognostic influence. One hundred and fourteen radical prostatectomies with small tertiary components, which mostly occupied less than 5% of whole tumours were analysed . These specimens were compared with a prostatectomy database which was comprised of 2,276 cases without a tertiary component. The pathologic stages of "typical" Gleason score 5 to 6 tumours (Gleason scores 2 + 3 = 5, 3 + 2 = 5, 3 + 3 = 6), which contained tertiary patterns 4 or 5, were significantly higher than those of "typical" Gleason score 5 to 6 tumours without pattern 4 (p = 0.018) but lower than those of "typical" Gleason score 7 tumours (p = 0.021; Gleason scores, 3 + 4 = 7, 4 + 3 = 7). Typical Gleason score 7 tumours with a tertiary pattern 5 showed significantly worse pathologic stages than typical Gleason score 7 tumours (p = 0.008) without pattern 5 and were not different statistically from typical Gleason score 8 (Gleason score, 4 + 4 = 8) tumours. Both typical Gleason score 5 to 6 and 7 tumours with tertiary components revealed significantly higher progression rates than typical Gleason score 5 to 6 tumours (p <0.0001) and Gleason score 7 tumours (p = 0.003) without tertiary components, and progressed like typical Gleason score 7 and 8 tumours respectively. Tertiary high-grade components seem to have an adverse impact on biological behaviour. The authors propose that the Gleason system for radical prostatectomy specimens be modified to take into account small volumes of patterns 4 and 5, which are important prognostically.

Reviewer: Matthias Winkler

Journal:	European Urology
Authors:	Salomon L, Hoznek A, Lefrere-Belda MA, Bellot J, Chopin DK and Abbou CC	Issue:	2000, 37(3): 297-300

Title:

Nondissection of pelvic lymph nodes does not influence the results of perineal radical prostatectomy in selected patients.

Abstract:
We know from retrospective studies that pelvic lymph node dissection can be dispensed with in selected men undergoing radical prostatectomy. The influence of nondissection of pelvic lymph nodes on tumour progression was prospectively evaluated in 100 perineal prostatectomies. Forty-three of the 100 patients (group 1) did not undergo pelvic lymph node dissection because their preoperative PSA level was below 10 ng/ml and the Gleason score of their positive biopsies was below 7. Group 1 was compared with 25 of the 114 patients operated on during the same period by the retropubic approach and who had pelvic node dissection and the same preoperative criteria (group 2: PSA <10 ng/ml and a Gleason score of positive biopsies <7). In groups 1 and 2 respectively, specimen weight was 44.5 and 54.3 g (p = 0.04), Gleason score was 6.2 and 5.6, tumour volume was 0.91 ml and 0.8 ml, 81.4% and 84% of patients were in stage pT2, 13.9% and 12% had extracapsular disease, 4.6% and 0% had seminal vesicle invasion, and 13.9% and 16% had positive surgical margins. The actuarial 5-year recurrence-free rate was 78% in group 1 and 80% in group 2 (p>0.05). From this small prospective study there is no evidence that the lack of pelvic lymph node dissection influences the intermediate term results of perineal radical prostatectomy in selected patients (preoperative PSA <10 ng/ml and Gleason score for positive biopsies<7).

Reviewer: Matthias Winkler

Journal:	European Urology
Authors:	Malavaud B, Villers A, Ravery V, Tollon C, Rischmann P, Charlet J, Plante P, Boccon-Gibod L and Sarramon JP	Issue:	2000, 37(3): 281-288

Title:

Role of preoperative positive apical biopsies in the prediction of specimen-confined prostate cancer after radical retropubic prostatectomy: a multi-institutional study.

Abstract:
The risk of positive margins increases when it is not possible to obtain a wide excision of periprostatic fascia, as at the apex. This study examines the prognostic value of positive preoperative apical biopsies for predicting positive surgical margins. A multi-institutional study of 280 radical prostatectomy specimens was undertaken to validate a nomogram developed for the prediction of specimen confined prostate cancer after prostatectomy. Biopsy Gleason score, prostate specific antigen (PSA) and apical location of positive biopsies that were identified with a previous logistic regression formula were collected. The predictive indexes of positive margins were compared with the actual margin status in terms of predictive characteristics. It was confirmed that positive apical biopsies (p<0.001), PSA (p<0.005) and the Gleason score (p<0.005) were strongly linked to the occurrence of positive margins. A cut off value of 0.5 gave an adequate compromise between sensitivity and specificity with respective values of 68% and 73% and a test accuracy of 72%. It was possible to predict 85% of negative margins, and to delineate two groups with different rates of positive margins (14.5% vs. 50%). Perhaps we should routinely include apical biopsies in our biopsy protocols?

Reviewer: Matthias Winkler

Journal:	International Journal of Cancer
Authors:	Latil A, Bieche I, Pesche S, Valeri A, Fournier G, Cussenot O and Lidereau R	Issue:	2000, 89:167-171

Title:

VEGF overexpression in clinically localised prostate tumours and neuropilin-1 overexpression in metastatic forms.

Abstract:
Angiogenesis seems to contribute to the pathogenesis of prostate cancer. This group examined 42 primary sporadic prostate tumors at different clinical stages, together with 3 prostate cancer cell lines (DU145, PC3 and LNCaP), for expression of VEGF and the gene encoding the recently identified VEGF165 isoform-specific receptor neuropilin-1, by using a quantitative reverse transcription (RT)-PCR method. Up-regulation of VEGF and neuropilin-1 was observed in 12 and 14 tumours, respectively. The VEGF165 isoform was slightly over represented in tumours that overexpressed VEGF. VEGF overexpression correlated with stage II disease (p < 0.05). Neuropilin-1 overexpression correlated with advanced disease (p < 0. 01) and a high Gleason grade (p < 0.02). This study may suggest that VEGF expression could be used as a prognostic marker in early-stage prostate tumors, whereas neuropilin-1 overexpression might be a marker of aggressiveness.

Reviewer: Matthias Winkler

Journal:	European Urology
Authors:	Schroeder FH, Kranse R, Dijk MA, van Kemenade M, de Jong FH, Blom JHM, Tijburg LBM, Westerstrate JA and Dagnelie PC	Issue:	2000, 37: 1-175

Title:

Tertiary prevention of prostate cancer by dietary intervention: results of a randomised, double blind, placebo controlled, crossover study.

Abstract:
Although good epidemiological evidence exists to suggest that dietary factors influence the progression of prostate cancer, there is very little clinical evidence. This elegant study evaluates a composite dietary supplement consisting of soya extract, green tea extract, phytosterols, carotenoids, selenium and vitamin E on the slope of 2log PSA of 37 men with rising PSA after radical treatment for confined prostate cancer. The effect of the supplement was tested against placebo during 2 crossover periods of 6 weeks. The slope of the normal rise of PSA during the verum periods decreased. PSA doubling times during placebo and verum periods amounted to 29.5 and 60 weeks (p<0.05). This is the first randomised, double blind, placebo controlled study of a dietary supplement in the tertiary prevention of prostate cancer which shows a relative advantage. The magnitude and duration of the response was encouraging. The effect did not seem to be related to endocrine parameters. Can this be translated into primary prevention and what is the active ingredient?

Reviewer: Matthias Winkler

Journal:	Seminars in Urologic Oncology
Authors:	Wei JT and Montie JE	Issue:	2000, 18(1): 76-80

Title:

Comparison of patients' and physicians' rating of urinary incontinence following radical prostatectomy.

Abstract:
Reported incontinence rates following a radical prostatectomy have been quite variable. It has been demonstrated that the physician's assessment of a patient's symptom does not correlate with the patient's own assessment. To further explore the differences in the reported outcomes between physicians and patients, the assessment of urinary incontinence in a cohort of men undergoing radical prostatectomy was evaluated. A total of 145 individuals completed a brief urinary continence questionnaire post-operatively at the 1-year anniversary of their operation and also had the physicians' assessment of incontinence documented in the medical record. Patient-reported incontinence rates varied from 13% to 65% depending on the definition of incontinence applied and the greatest agreement was seen when the physicians' assessment of incontinence was compared with the patient's report of pad use and urinary bother. These comparisons resulted in only moderate to good levels of agreement, which suggests that a more reliable and accurate means to evaluate urinary incontinence following radical prostatectomy needs to be developed.

Reviewer: Matthias Winkler

Journal:	Journal of Urology
Authors:	Presti JC, Chang JJ, Bhargava V and Shinohara K	Issue:	2000, 163: 163-167

Title:

The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial.

Abstract:
This prospective study demonstrates that extenuated field biopsies (including fare lateral peripheral zone biopsies) are ultimately better than traditional sextant biopsies which missed 20% of the cancers. This and the recent evidence that extended field biopsy regimens do not cause more discomfort and major complications calls for a change in clinical practice.

Reviewer: Matthias Winkler

Journal:	British Journal of Cancer
Authors:	Schroder FH, Collette L, de Reijke TM and Whelan P	Issue:	2000, 82: 283-90

Title:

Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organisation for Research and Treatment of Cancer.

Abstract:
As pharmacological androgen blockade has become established as a treatment for asymptomatic metastatic prostate cancer, research has begun to concentrate on the side-effects of such treatments and the consequent quality of life for such patients. Many authors have suggested that non-steroidal anti-androgens as single agents offer effective androgen blockade with fewer negative effects on libido and erectile function. This paper reports the sexual function data from EORTC protocol 30892 which randomised 310 patients to monotherapy with either the non-steroidal anti-androgen flutamide or the steroidal anti-androgen cyproterone acetate. Median age was 71 and sexual function was assessed via an investigator-administered questionnaire at three-month intervals. At the start of the trial, sexual activity was similar in both groups with about half experiencing nocturnal penile tumescence and about one third having on-going sexual relations. After commencement of anti-androgen therapy, a decline in sexual function was seen with 80-90% of previously potent patients in both treatment groups eventually losing potency. There was no statistically significant difference in the data from the flutamide and cyproterone arms. Interestingly, it took several months for impotence to develop with either therapeutic option; perhaps the intermittent use of androgen blockade with either agent might delay this further or even prevent it. This study offers useful information because it is a prospective randomised controlled trial with a reasonable duration of follow-up. Patient and physician choices regarding androgen ablation need information from this type of trial in order to assess the merits of the various androgen-ablative regimens on offer.

Reviewer: Kieran Jefferson

Journal:	Med Decis Making
Authors:	Mazur DJ, Hickam DH and Mazur MD	Issue:	1999, 19: 394-398

Title:

How patients' preferences for risk information influence treatment choice in a case of high risk and high therapeutic uncertainty: asymptomatic localized prostate cancer.

Abstract:
Counselling of patients with asymptomatic confined prostate cancer in regard to treatment options is influenced by the type of information given. This study assesses how patients' preferences for non-numerical risk information are related to their tendency to choose early surgical treatment for asymptomatic gland-confined prostate cancer. The authors conducted a cross-sectional study of 228 patients receiving continuing care in a general medicine clinic. After being provided with three data disclosures related to the treatment decision, subjects were given a choice between surgery now and watchful waiting. Data about surgical complications were presented in numerical format. The subjects were also asked whether they preferred communication with their physician about the chance (probability) of adverse outcomes related to management strategies in terms of words (such as possible or probable) or numbers (such as percentages). Of the 226 patients who chose either surgery now or watchful waiting, 71.2% preferred risk information in terms of words only or numbers only, 44% words only, and 56% numbers only. Younger patients (OR = 1.06 per year; CI = 1.02-1.10, P = 0.0008) and those wanting risk communication in terms of words only (OR = 2.41; CI = 1.24-4.70, P = 0.01) tended to prefer surgery now over watchful waiting as the management strategy for asymptomatic gland-confined prostate carcinoma. The authors conclude that there is a significant association between patients' preferences for risk communication with their physicians in terms of words only and a tendency to prefer early surgical intervention for prostate cancer when surgical risk data are provided numerically. Different types of risk communication may potentially introduce bias in the patients decision making process.

Reviewer: Matthias Winkler

Journal:	BJU International
Authors:	Egawa S, Ohori M, Iwamura M, Kuwao S and Baba S	Issue:	1999, 84: 815-820

Title:

Efficacy and limitations of delayed/salvage radiation therapy after radical prostatectomy.

Abstract:
This study assesses the kinetics of prostate specific antigen (PSA) and the degree of PSA suppression, to better understand the efficacy and limitations of delayed/salvage radiation therapy after radical prostatectomy. The PSA doubling time was calculated in patients with biochemical failure after radical prostatectomy and in those who underwent delayed/salvage radiation therapy. Patients in whom PSA was undetectable by conventional assay after irradiation were followed using a hypersensitive PSA assay. Of 125 patients who underwent radical prostatectomy for clinically resectable prostate cancer, 47 developed biochemical failure at a mean of 11.8 months after surgery and 38 of these underwent radiotherapy (36 for isolated biochemical failure and 2 for local progression with elevated PSA levels). The mean (SD) PSA doubling time after surgery was 14.6 (16.2) months (n=44) and after radiation therapy it was 13.3 (23.9) months (n=32). Eleven of 30 evaluable patients (37%) had a sustained PSA suppression lasting at least 12 months after radiotherapy. Only the time to biochemical failure after surgery approached statistical significance for predicting a durable response to radiotherapy (P=0.08). The rapidity with which PSA levels double after surgery may provide a clinically significant indication of the nature of these recurrent tumours, which deserve the best possible attempt at cure. Slow-growing tumours with longer PSA doubling times may be better candidates for delayed/salvage radiation therapy. Larger studies involving more patients are needed to determine whether the PSA doubling time can define subgroups for which specific treatment strategies should be developed.

Reviewer: Matthias Winkler

Journal:	Med Care
Authors:	Wilt TJ, Cowper DC, Gammack JK, Going DR, Nugent S and Borowsky SJ	Issue:	1999, 37(10): 1046-56

Title:

An evaluation of radical prostatectomy at Veterans Affairs Medical Centers: time trends and geographic variation in utilization and outcomes

Abstract:
Temporal trends and geographic variation in utilization of radical prostatectomy (RP) as well as 30-day mortality and complication rates were examined in this study. A total of 13,398 men aged 45 to 84 years underwent RP at Veterans Affairs Medical Centers. From 1986 to 1996, the annual number of RP at VAMCs (range, 695-1,545 RP) more than doubled, and the rate of RP at VAMCs per male VA user increased by 40% (range, 48/100,000-66/100,000). Geographic variation in utilization decreased during the period between 1986 and 1996, but a twofold difference in RP utilization in 1996 remained between high- and low-utilization divisions. Major cardiopulmonary complications, vascular complications, and colorectal injuries occurred in 1.7%, 0.2%, and 1.8% of men respectively. Thirty-day mortality was 0.73%, it declined from 1986 to 1996, and was associated with a history of diabetes and congestive heart failure. Differences in utilization may be caused by uncertainty regarding the effectiveness of early detection and treatment of prostate cancer.

Reviewer: Matthias Winkler

Journal:	Aust N Z J Surg
Authors:	Gerard JP, Xie C, Carrie C, Romestaing P, Pommier P, Mornex F, Clippe S, Sentenac I and Ginestet C	Issue:	1999, 69: 707-711

Title:

Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon.

Abstract:
Conformal radiotherapy has been introduced recently in an attempt to improve the results of external beam radiation therapy (EBRT). The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. In the EBRT group of 231 patients, the5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. The curative treatment of patients with prostate cancer using EBRT gives good long-term survival comparable to radical prostatectomy series. Rectal toxicity is low. Conformal radiotherapy continues to be a promising approach to improve local control and perhaps survival.

Reviewer: Matthias Winkler

Journal:	British Journal of Cancer
Authors:	Blok LJ, Chang GT, Steenbeek-Slotboom M, van Weerden WM, Swarts HG, De Pont JJ, van Steenbrugge GJ and Brinkmann AO	Issue:	1999, 81(1):28-36

Title:

Regulation of expression of Na+,K(+)-ATPase in androgen-dependent and androgen-independent prostate cancer

Abstract:
The main function of Na+,K(+)-ATPase is to maintain sodium and potassium homeostasis in animal cells. The resulting electrochemical gradient is facilitative for transport of several compounds (cisplatin) over the cell membrane. Cisplatin is a chemotherapeutic agent experimentally used in the treatment of hormone-refractory prostate cancer. This group observes that a ouabain-induced decrease of Na+,K(+)-ATPase activity in androgen-dependent human prostate cancer cells (LNCaP-FGC) results in reduced sensitivity of these cells to cisplatin-treatment. Surprisingly, androgen-induced decrease of Na+,K(+)-ATPase expression, did not result in significant protection against the chemotherapeutic agent.

Reviewer: Matthias Winkler

Journal:	Cancer Research
Authors:	Jacob K, Webber M, Benayahu D and Kleinman HK	Issue:	1999, 59(17):4453-4457

Title:

Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone

Abstract:
The mechanism underlying the "organ-specific" metastasis of prostate cancer cells to the bone is still poorly understood. It is not clear whether the cells only invade the bone and proliferate there or whether they invade many tissues but survive mainly in the bone ("seed and soil"). Extracts from various organs were used as chemoattractants in the in vitro chemotaxis and invasion assays by this group. It was shown that, in comparison with extracts of other tissues, bone extracts promote a 2- to 4-fold increase in chemotaxis by human prostate epithelial cells and a 4-fold increase in the invasive ability of human prostate carcinoma cells. The purified active factor from bone and from marrow stromal-cell-conditioned medium is a low glycosylated osteonectin that specifically promotes the invasive ability of bone-metastasizing prostate cancer cells but not that of non-bone-metastasizing tumour cells. It is further concluded that prostate cancer cell metastasis to the bone is, in part, mediated by the ability of osteonectin to promote migration, protease activity, and invasion because osteonectin specifically enhances matrix metalloprotease activity in prostate cells.

Reviewer: Matthias Winkler

Journal:	European Urology
Authors:	Iversen P	Issue:	1999, 36: 20-26

Title:

Quality of life issues relating to endocrine treatment options

Abstract:
Hormone therapy in prostate cancer is increasingly used for both the management of patients with non-metastatic disease and as a neoadjuvant or adjuvant to curative therapies. This has resulted in patients with fewer symptoms being treated for longer periods of time. Quality of life issues in these patients are at least as important as conventional measures of outcome. Endocrine treatments for prostate cancer, such as castration, combined androgen blockade and non-steroidal antiandrogen monotherapy, have shown similar results in terms of time to progression and survival. The main difference between these treatments is their impact on patients' quality of life. Data from two large studies of bicalutamide monotherapy show that this non-steroidal antiandrogen is associated with significant health-related quality of life advantages in the treatment of patients with locally advanced (M0) disease compared with castration, suggesting that this treatment may benefit patients with early disease. Bicalutamide was favoured in 8 out of 9 evaluable quality of life dimensions, and this was statistically significant for sexual interest and physical capacity. This review highlights the fact that endocrine treatments with minimal adverse effects on quality of life are likely to be favoured by patients with non-metastatic disease who are being treated for longer periods of time.

Reviewer: Matthias Winkler

Journal:	Technical Urology
Authors:	Djavan B, Susani M, Bursa B, Basharkhah A, Simak R and Marberger M	Issue:	1999, 5(3): 139-142

Title:

Predictability and significance of multifocal prostate cancer in the radical prostatectomy specimen.

Abstract:
Multifocal prostate cancer has been reported in 50-76% of all cases of radical retropubic prostatectomy (RRP) specimens, but the clinical and prognostic significance of this finding is still unclear. The authors present a retrospective analysis of patients who underwent RRP between 1993 and 1997. Preoperative screening parameters and 4-mm RRP specimen sections were examined. The location, Gleason score, and extracapsular extension of the tumor were recorded. Three hundred and eight cases were reviewed with a mean follow-up of 4.2 +/- 1 years (range 2-6 years). Two hundred six patients (66.9%) had multifocal prostate cancer and 102 (33.1%) had unifocal prostate cancer. Of those with multifocal disease, 63% had two foci and 37% had three or more foci. There were statistically significant differences between both groups with respect to preoperative prostate-specific antigen (PSA) density of the transition zone (PSA-TZ), free/total (f/t) PSA, as well as percentage of patients with organ confined disease, high-grade tumors, and local recurrence. PSA-TZ (P = 0.001) and f/t PSA (P = 0.004) were significantly different between patients with unifocal and multifocal disease (0.9 vs. 2.2 ng/ml/cc and 18% vs. 6.5%, respectively). These data suggest that multifocal prostate cancer is associated with higher grade, stage, and recurrence rate than unifocal prostate cancer.

Reviewer: Matthias Winkler

Journal:	Journal of Urology
Authors:	Perrotte P, Litwin MS, McGuire EJ, Scott SM, von Eschenbach AC and Pisters LL	Issue:	1999, 162(2): 398-402

Title:

Quality of life after salvage cryotherapy: the impact of treatment parameters

Abstract:
The fundamental principles of treating recurrent prostate cancer are giving way to an approach that increasingly attempts to balance quality and quantity of life. Cryotherapy has emerged as a promising salvage therapy option for treatment of locally recurrent prostate cancer after initial therapy. This retrospective study evaluates patient quality of life after salvage cryotherapy and correlates complications impairing quality of life with specific cryotherapy treatment parameters. A modified UCLA Prostate Cancer Index measuring health related quality of life was used on 150 patients who underwent salvage cryotherapy. The relationships among incontinence, pain, impotence, sloughing of tissue and problematic voiding symptoms, and cryotherapy treatment parameters, including use of a urethral warming catheter, number of cryotherapy probes and number of freeze-thaw cycles was evaluated. Only 112 (74%) surveys were returned. Mean follow-up was 16.7 months (range 0.5 to 31.5). Treatment without an effective urethral warming catheter was highly associated with urinary incontinence (p<0.003), perineal pain (p<0.001) and issue sloughing (p<0.003). Impotence was higher in the double freeze-thaw cycle group (p<0.05). Overall, satisfaction with cryotherapy was 33%. Quality of life may be compromised in a substantial number of patients following salvage cryotherapy. Effective urethral warming is essential in reducing complications and maximizing quality of life. Salvage cryotherapy does not appear to offer any quality of life advantages compared to salvage prostatectomy.

Reviewer: Matthias Winkler

Journal:	Cancer Causes Control
Authors:	Nilsen TI and Vatten LJ	Issue:	1999, 10(4):269-275

Title:

Anthropometry and prostate cancer risk: a prospective study of 22,248 Norwegian men.

Abstract:
Not many risk factors for prostate cancer are known, but both endocrine changes and dietary factors have been implicated in the etiology of the disease. Anthropometry is said to provide a tool in the search for carcinogenic mechanisms connected to these suggested causal components. The association between body size and prostate cancer risk in a prospective study of 22,248 Norwegian men was evaluated. Six hundred and forty two men developed cancer of the prostate during the 12 years of follow up. No significant trend for height, weight, body mass index (BMI), and lean body mass (LBM)) was observed. However, an excess risk of prostate cancer with increasing height was suggested by an age-adjusted relative risk of 1.2 (95% CI = 0.9-1.6) for the tallest compared to the shortest quintile of men. According to this well conducted study there seems to be no strong association between anthropometric factors and risk of prostate cancer.

Reviewer: Matthias Winkler

Journal:	Journal of the American Medical Association
Authors:	Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD and Walsh PC	Issue:	1999, 281: 1591-1597

Title:

Natural history of progression after PSA elevation following radical prostatectomy

Abstract:
This study was performed to describe the natural history of patients who develop a raised PSA after radical prostatectomy. At Johns Hopkins between 1992 and 1997, the PSA became greater than 0.2 ng/ml in 304 of 1997 men and 103 developed metastases. The actuarial metastasis-free survival for all men was 82% at 15 years and the median time to the development of metastases after PSA elevation was 8 years. An algorithm was constructed to create risk groups for the development of metastatic disease using time to PSA rise (more or less than 2 years), Gleason score (5 to 7 cf. 8 to 10) and PSA doubling time (more or less than 10 months). The PSA doubling time was not a statistically significant predictor for men with a Gleason score greater than 7 when the time to PSA failure was known. The median time to death after the development of metastases was 5 years and none within the study died from other causes if metastases were present. A single surgeon in a tertiary referral teaching hospital performed all the radical prostatectomies. It is important that the algorithm is examined in a test set from a general population treated by a number of different surgeons to assess its general applicability. Nevertheless, the data suggest that patients with PSA recurrence may have an extended time period to the development of metastases and that additional therapy may not be needed for a considerable time.

Reviewer: Marc Laniado

Journal:	Journal of the American Medical Association
Authors:	Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD and Walsh PC	Issue:	1999, 281(17): 1591-1597

Title:

Natural history of progression after PSA elevation following radical prostatectomy

Abstract:
This paper is compulsory reading for anyone who deals with follow-up of radical prostatectomy patients. What does a rising PSA that has been undetectable post radical prostatectomy mean for the patient and for the clinician? This question is central to a careful characterization of disease progression in men with biochemical recurrence who were kept in a stringent follow-up protocol that only allowed treatment for symptoms of proven metastatic disease. The information provided in this paper allows us to put treatment failure in perspective. For instance, a rising PSA level after radical prostatectomy is not a death warrant for most patients. Not all patients with relapsed disease need immediate intervention or treatment. In this study, 1997 men undergoing radical prostatectomy were reviewed retrospectively. The median follow-up was 5.3 years but only 17% of patients had been followed up for more than 10 years. Fifteen percent developed biochemical PSA level elevation. Of these, 136 had biochemical recurrence within 2 years, 108 between 2 and 5 years and 71 after 5 or 10 years. This indicates the importance of continued follow-up, in contrast to the results of some other studies. Only 8% of patients had high-grade disease reflecting a rigorous selection policy. Four percent of patients with organ-confined disease experienced recurrence, as opposed to 62% of patients with a Gleason tumor score of between 8 and 10. The median actuarial time to metastases was 8 years from time of PSA level elevation, yet 63% of the patients with rising PSA values remained free of metastases at 5 years. No patient with a Gleason tumor score of less than 6 developed metastatic disease. This underlines the importance of appropriate patient selection. An algorithm constructed to predict metastatic progression for high and low risk patients was developed. Combining time to recurrence of PSA and high grade histology, the proportion of patients with metastases at 3, 5, and 7 years was 23%, 40% and 53% respectively, if the time to recurrence was greater than 2 years. If the time to recurrence was less than 2 years then the proportion of patients with metastases at 3, 5, and 7 years was 47%, 69% and 79%. The interval from surgery to the documentation of metastasis was predictive of death from prostate cancer once metastatic disease had occurred. The 5-year survival rate was only 13% for patients who developed metastatic disease within 3 years, while those who developed metastases more than 8 years after surgery had a 5-year survival of 78%. The long interval between documentation of biochemical progression and clinical metastatic disease implies that much of the investigation performed at the time of biochemical relapse can be eliminated. Due to the small population size some of the findings have to be viewed with caution. The lack of an association between high-grade histology and metastatic progression does not mean that the tumor grade would not be predictive if a larger population were evaluated.

Reviewer: Matthias Winkler

Journal:	Journal of the American Medical Association
Authors:	Shipley WU, Thames HD, Sandler HM, Hanks GE, Zietman AL, Perez CA, Kuban DA, Hancock SL and Smith CD	Issue:	1999, 281(17): 1598-1604

Title:

Radiation therapy for clinically localized prostate cancer - a multi-institutional pooled analysis.

Abstract:
To counsel a patient with localized prostate cancer about treatment options requires solid data on outcome for each treatment option. This group delivers a multi-institutional pooled analysis of 1765 men treated with external beam radiation alone and reports the PSA information for up to 9 years of follow-up. PSA failure rates after 5 and 7 years for patients with a presenting PSA of less than 10% were 77.8% and 72%, respectively. Five-year survival, disease-specific survival, and freedom from biochemical failure were 85%, 95.1% and 65%, respectively. Derived by recursive partitioning, 4 prognostic subgroups were identified. Patients with a pre-treatment PSA of < 9.2 have an 81% 5-year survival free of biochemical failure, as compared to 29% for patients with an initial PSA of >19.7 and a Gleason score of 7 - 10. These pooled estimated PSA control rates are similar to those of single institutions and are a good basis for evidence based counseling of prostate cancer patients until the results of well-controlled, prospective, randomized studies are available.

Reviewer: Matthias Winkler

Journal:	Urology
Authors:	Klotz LH, Goldenberg SL, Jewett M, Barkin J, Chetner M, Fradet Y, Chin J and Laplante S	Issue:	53(4): 757-763

Title:

CUOG randomised trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results

Abstract:
Patients undergoing radical prostatectomy were randomized to surgery alone or to receive a prior 12-week course of cyproterone acetate (300 mg/day). Patients were stratified by stage, PSA, and Gleason score. Outcome was measured by biochemical progression. There was no difference in the probability of progression between the two groups overall. Following subset analysis, the probability of progression was lower in patients with a baseline PSA in the range 25 – 50 ng/ml. The authors also reported a lower incidence in positive margin rate for patients receiving CPA pre-op. They do, however, question the validity of this finding. Overall the authors conclude that neoadjuvant therapy either does not confer a biochemical survival benefit or the study was not sufficiently powerful enough to demonstrate an effect.

Reviewer: Jon Cartledge

Journal:	Urology
Authors:	Zelefsky MJ, McKee AB, Lee H and Leibel SA	Issue:	53(4): 775-778

Title:

Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate

Abstract:
The patients in this trial were derived from a group of 1,050 men that underwent conformal radiotherapy for clinically localised prostate cancer. Of these, 265 were seen at routine follow up. Of this group, 75 were previously potent and had already requested and tried sildenafil. Fifty of these reported that they used the medication and are therefore included in this paper (4.7% of the original group). The authors report that the degree of sexual impairment pre-treatment is the most important predictor of success, with 90% of patients with partial erections reporting success, compared to 52% of those with no erections. Using data from this self-selected group of patients, the authors conclude that sildenafil improves erectile function in 66% of patients with post radiotherapy impotence.

Reviewer: Jon Cartledge

Journal:	Cancer
Authors:	Polascik TJ, Manyak MJ, Haseman MK, Gurganus RT, Rogers B, Maguire RT and Partin AW	Issue:	1999, 85: 1586-1592

Title:

Comparison of clinical staging algorithms and 111Indium-capromab pendetide immunoscintigraphy in the prediction of lymph node involvement in high risk prostate carcinoma patients

Abstract:
The need to identify lymph node deposits in patients suitable for radical prostatectomy is important because the actuarial 10-year metastasis-free survival falls from 99% to 68% with micrometastases to the lymph nodes. Clinical algorithms to predict positive lymph nodes include preoperative PSA, Gleason pattern on prostate biopsies and clinical stage. Sensitivity ranges from 90% upwards but with specificity of 30% or less in prior studies. This study evaluated patients judged to be at high risk of lymph node metastases. The Prostascint scan uses an antibody to an epitope of prostate specific membrane antigen inside the cell which can be detected when cells are damaged. This study evaluated mostly Caucasian patients with T2 to T3 disease, mean age 56 years, mean PSA 57 and mean biopsy Gleason score 7.1 Using a combination model of Prostascint scan result and clinical algorithm, a positive result increased the probability of lymph node deposits from 0.39 to 0.72 and a negative result decreased the probability to 0.25. The critical questions are: what are the probability thresholds that will alter management; at what probability are lymph node deposits so unlikely that a radical prostatectomy can be performed without question or lymph node deposits so likely that curative surgery should not be attempted? Between those two thresholds it may be necessary to perform additional investigations such as a staging lymphadenectomy. Even a negative result in such a population would mean that 1 in 4 patients would avoid a radical prostatectomy by a staging lymphadenectomy.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Kallakury BV, Sheehan CE, Rhee SJ, Fisher HAG, Kaufman RP, Rifkin MD and Ross JS	Issue:	1999, 85: 1569-1576

Title:

The prognostic significance of proliferation associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2

Abstract:
This study evaluated whether p34 cyclin dependent kinase (cdk) (a cell cycle protein that regulates progression from G2 to M phase) was an additional explanatory variable in predicting disease recurrence either because it was a surrogate marker of proliferation or for other reasons. Immunohistochemical staining of radical prostatectomy specimens was performed for p34 cdk and associated cell cycle proteins (p120, cyclin A and B1) and proliferation markers (Ki-67, proliferating cell nuclear antigen). A multivariate analysis was performed including PSA, pathological stage and Gleason score to predict disease recurrence determined by a PSA > 0.4 on two occasions. P34 cdk and pathological stage were the only independent explanatory variables in the analysis, suggesting a potential use in clinical practice dependent on further studies. Other proliferation markers alone were not additional explanatory variables, suggesting that p34 cdk has specific properties of importance.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Liebross RH, Pollack A, Lankford SP, Zagars GK, von Eschenbach AC and Geara FB	Issue:	1999, 85: 1577-1585

Title:

Transrectal ultrasound for staging prostate carcinoma prior to radiation therapy: an evaluation based on disease outcome

Abstract:
This study evaluated whether staging by transrectal ultrasound (TRUS) was a prognostic variable of importance in determining the outcome after radical radiotherapy with curative intent when compared with staging by digital rectal examination (DRE) alone. The study did not find any benefit of TRUS. This is not surprising as TRUS and DRE are unable to determine microscopic pathological extraprostatic extension and negative results do not lower the prior probability of this significantly.

Reviewer: Marc Laniado

Journal:	Journal of Urology
Authors:	Maillefert JF, Sibilia J, Michel F, Saussine C, Javier RM and Tavernier C	Issue:	1999, 161: 1219-1222

Title:

Bone mineral density in men treated with synthetic gonadotrophin-releasing hormone agonist for prostatic carcinoma

Abstract:
The authors evaluate the relationship between gonadotrophin-releasing hormone agonists and bone density in 12 men with prostate cancer. Bone density for both lumber and femoral neck bone decreased over time although the reduction in bone density did not reach statistical significance. Serum osteocalcin, a marker of bone turnover, increased significantly by 12 months, suggesting accelerated bone turnover. No pathological fractures were observed over the 18-month study period.

Reviewer: Andrew Elves

Journal:	Journal of the American Medical Association
Authors:	Stamey TA, McNeal JE, Yemoto CM, Sigal BM and Johnstone IM	Issue:	1999, 281: 1395-1400

Title:

Biological determinants of cancer progression in men with prostate cancer

Abstract:
This study from Stanford evaluated the variables predicting a PSA > 0.07 following a radical prostatectomy. Between 1983 and 1992, 600 radical prostatectomies were performed by faculty surgeons from which sufficient data were available from 379. Patient follow up was a median and mean 5 years and survival analyses were constructable for up to 7 years. Eight morphological outcome criteria were applied blindly. These included percentage of each cancer occupied by Gleason score 4/5, cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin and preoperative PSA level. If multiple cancers were present the largest cancer was selected for study. In a Cox proportional hazards model only log10 cancer volume, log10 Gleason grade 4/5 % cancer, positive lymph nodes and log10 vascular invasion were significant. The cumulative failure increased steeply with percentage Gleason grade 4/5 cancer, which was present in 81% of specimens. Men with no Gleason grade 4/5 had a cumulative failure rate of 5.6% but this rose to almost 50% with 50% Gleason grade 4/5. Thirty percent of men had no evidence of progression despite greater than 41% grade 4/5 cancer, but their cancer volumes were much smaller. Failure rates were 14% for tumours of 0.5 to 2.0 ml and 97% for tumours of 6.0 to 12.0 mls. Interestingly, PSA, extraprostatic extension and positive surgical margins were not significant in this model, probably because of correlation with cancer volume, which was more significant. These data suggest that patients with localised cancer of high volume or grade are likely to fail biochemically after radical prostatectomy. It is still possible that the majority might not suffer additional morbidity attributable to operation and indeed, untreated, their outcome might be worse.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Matsushima H, Goto T, Hosaka Y, Kitamura T and Kawabe K	Issue:	1999, 85: 1822-1827

Title:

Correlations between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation

Abstract:
The relationship between intratumoral microvessel density and apoptosis in prostate cancer is unknown although inhibition of angiogenesis induces further apoptosis in androgen dependent and independent states. This study attempted to draw conclusions based on histological observations of radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy. There was a significant inverse relation between apoptosis and angiogenesis in untreated patients compared to a positive relationship in treated patients. It is not certain whether hypervascular tumours were more likely to undergo apoptosis when deprived of androgens. Although there was a three-fold increase in apoptosis and 60% fall in proliferation, there was no difference in angiogenesis per se in treated and untreated patients. A hypothesis that short-term androgen ablation induces apoptosis in hypervascular tumours more commonly might be suggested from these observations. The authors suggest that angiogenesis inhibitors should not be used until tumours become hormone refractory because inhibition of vascularisation might reduce the sensitivity of the tumours to hormone ablation.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Kallakury BV, Sheehan CE, Rhee SJ, Fisher HA, Kaufman RP Jr, Rifkin MD and Ross JS.	Issue:	1999, 85: 1569-1576

Title:

The prognostic significance of proliferation-associated nuclear protein p120 expression in prostate adenocarcinoma - A comparison with Cycline A and B1, Ki-67, Proliferating cell nuclear antigen, and p34 cdc2.

Abstract:
This is a further attempt to identify prognostic parameters that can separate the aggressive tumours from the relatively indolent ones to aid allocation of treatment options. Previously, the group showed that p34cdk, a G2M regulator, predicts disease recurrence independently after radical prostatectomy. This paper tries to evaluate the immunohistochemical profile of further cell proliferation markers. Significant coexpression was noted and p120, cyclin A and p34cdk correlated with disease recurrence. Proliferation-associated nuclear protein p120 appears to be an additional marker of aggressive disease in prostate cancer. This study supports further work into the possible therapeutic role of blocking the functions of cell proliferating proteins.

Reviewer: Matthias Winkler

Journal:	Urology
Authors:	Gao CL, Maheshwari S, Dean RC, Tatum L, Mooneyhan R, Connelly RR, McLeod DG, Srivastava S and Moul JW	Issue:	1999, 53(4): 714-721

Title:

Blinded evaluation of reverse transcriptase-polymerase chain reaction prostate-specific antigen peripheral blood assay for molecular staging of prostate cancer.

Abstract:
The use of RT-PCR PSA assay for staging of prostate cancer is highly controversial. Here, a very stringent protocol is followed for performing PCRs on 85 patients prior to radical prostatectomy, 22 control human subjects and 12 patients with locally advanced or advanced disease, to prevent any contamination. There was no correlation of RT-PCR detected PSA-expressing cells before radical prostatectomy with pathologic stage and grade or early PSA recurrence. This questions the hypothesis that circulating PSA-expressing cells equates to circulating tumour cells and, therefore, occult metastases.

Reviewer: Matthias Winkler

Journal:	Journal of the American Medical Association
Authors:	Stamey TA, McNeal JE, Yemoto CM, Sigal BM and Johnstone IM	Issue:	1999, 281: 1395-1400

Title:

Biological determinants of cancer in men with prostate cancer.

Abstract:
The annual mortality of prostate cancer is second only to lung cancer, and yet only a fraction of untreated men will die from it. This paper addresses the need to find better ways to distinguish patients with innocuous disease from those that need treatment to eradicate the disease and from those for whom curative treatment would ultimately fail. The authors undertook a retrospective analysis of selected morphological and clinical variables and a modified version of Gleason grade and their association with disease progression after radical prostatectomy. Three hundred and seventy nine men with prostate cancer in the peripheral zone were selected from a series of 600 consecutive radical prostatectomies. The number of exclusions was very high. Biochemical progression, as indicated by a serum PSA level of 0.07% or more was the main outcome measure. Both median and mean follow-up time for the 379 men was 5 years. Data were analyzed in a quantitative way using the Cox proportional hazards model. It was shown that percentage Gleason grade 4/5, a new modification of the Gleason grading system, has a greater significance than any of the other variables (vascular invasion, cancer volume, positive lymph nodes, serum PSA, prostate weight, intraductal cancer and capsular penetration). The cumulative failure rate was only 5.6% for the 19% of patients who had no evidence of any Gleason grade 4/5 cancers. This low failure rate may imply that surgery is not needed for this patient group. The authors suggest a move away from the Gleason scoring system to simply estimating the percentage Gleason grade 4/5 in core biopsy specimen. They have previously reported a good correlation (R2=0.63) of percentage Gleason grade in biopsy specimen with the cancer within the prostate. If the biopsy specimen contained at least 20% Gleason grade 4/5 cancer then the prostate also contained at least 20% Gleason grade 4/5 in 90% of men. It is hoped that percentage Gleason grade 4/5 rather than the traditional Gleason score can contribute to ending the debate about which patients with prostate cancer should be treated. Furthermore, it seems that prostate cancer volume is a highly significant and independent determinant of biochemical failure suggesting that volume might have greater significance than PSA level as an independent predictor. We need new and refined techniques to measure cancer volume and percentage Gleason 4/5 to predict cancer progression better.

Reviewer: Matthias Winkler

Journal:	Urology
Authors:	Klotz LH, Goldenberg SL, Jewett M, Barkin J, Chetner M, Fradet Y, Chin J and Laplante S	Issue:	1999, 53(4): 757-763

Title:

CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results.

Abstract:
Neoadjuvant therapy has been shown in recent studies to produce up to 50% reduction in positive surgical margins. This reduction could not be translated into a better disease-specific survival. This paper evaluates the impact of neoadjuvant CPA 12 weeks prior to radical prostatectomy on biochemical progression in a prospective, randomized, open-label, controlled multicenter study. Two hundred and thirteen patients were randomized to either surgery alone or CPA before surgery. The probability of biochemical progression after 36-month follow-up was similar in both groups. It is doubtful however, whether this study with only a sample size of 100 patients in each arm and a power of 50% will ever detect a significant difference.The benefit of neoadjuvant androgen ablation remains uncertain.

Reviewer: Matthias Winkler

Journal:	Journal of Urology
Authors:	Rabbani F, Perrotti M, Bastar A and Fair WR	Issue:	1999, 161: 847-852

Title:

Prostate specific doubling time after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy.

Abstract:
Pre-operative neoadjuvant androgen deprivation therapy has been shown to reduce the incidence of non-organ confined disease in randomised studies. However, this does not appear to translate into improved PSA relapse survival benefit. The authors retrospectively reviewed a cohort of 1,462 patients undergoing radical prostatectomy with or without neoadjuvant androgen deprivation to determine the predictors of PSA doubling time. When stratified by pre-treatment PSA, clinical stage and biopsy grade, differences in PSA doubling time were significantly longer for those patients with a PSA between 4.1 to 10 ng/ml. In this group, the PSA doubling time was 7.6 +/- 1.0 months for those receiving neoadjuvant androgen deprivation versus 15.6 +/- 2.6 months for those treated with radical prostatectomy alone. The method of neoadjuvant androgen deprivation is not described but, given the prolonged effects of some forms of neoadjuvant androgen deprivation upon serum testosterone, this finding is unexpected.

Reviewer: Andrew Elves

Journal:	Cancer
Authors:	Cheng L, Bergstralh EJ, Scherer BG, Neumann RM, Blute ML, Zincke H and Bostwick DG	Issue:	1999, 85: 1300-1304

Title:

Predictors of cancer progression in T1A prostate adenocarcinoma.

Abstract:
The prognosis of patients with T1A prostate cancer is uncertain. This study from the Mayo clinic analysed features in patients with T1a cancer and survival to determine what factors might be important. All TURP specimens between 1960 and 1970 were analysed and 119 were found to have prostate cancer meeting the American Joint Committee on Cancer (AJCC) 1997 criteria for T1A cancer defined as 5% of cancer in the resected tissue. Mean patient age was 69 and median resected tissue was 18 g. In a multivariate analysis of survival, only the weight of TURP specimen was significant (0.04). Patients with TURP weight > 30 had 100% progression-free survival at 10 years compared to 73% if the specimen was less than 12 g. There was a tendency for tumour involving less than 3 chips to be less important (P=0.16). Patient age, Gleason score, cancer volume, number of cancer foci and high grade prostatic intraepithelial neoplasia were not additional explanatory variables. It may be that low weight of TURP resection specimen represents undersampling of the prostate and that tumours were really T1B and not T1A. There was no test set to examine these findings and these issues need to be resolved, but with PSA testing now possible, most people will probably follow this to guide management.

Reviewer: Marc Laniado

Journal:	Journal of Urology
Authors:	Adolfsson J, Steineck G and Hedlund PO	Issue:	1999, 161: 505-508

Title:

Deferred treatment of locally advanced nonmetastatic prostate cancer: a long-term follow-up

Abstract:
The authors report the 5 and 10 year survival of 50 patients with clinical stage T3 Nx M0 tumours managed by watchful waiting. Actual (cumulative incidence) overall and disease specific survival rates at 5 and 10 years were 68% and 90%, and 34% and 74% respectively. A third of patients had not received anti-tumour therapy at follow-up or before death.

Reviewer: Andrew Elves

Journal:	Urology
Authors:	Sanda M, Smith D, Charles L, Hwang C, Pienta K, Schlom J, Milenic D, Panicali D and Montie J	Issue:	3(2): 260-266

Title:

Recombinant vaccinia-psa (prostvac) can induce a prostate-specific immune response in androgen-modulated human prostate cancer

Abstract:
In this phase I trial, the authors gave a single dose of recombinant-PSA vaccine to men with prostate cancer and rising PSA after radical prostatectomy. All men were androgen sensitive having shown a PSA response to androgen blockade. Vaccinia-PSA (prepared by genetic modification of smallpox virus to include the human PSA gene) was given on the same day as the due dose of monthly zoladex, which was then stopped. PSA and testosterone levels were monitored. The authors report a variable response in the return of testosterone which was followed by a rise in serum PSA in all but 1 patient. Toxicity was minimal. They conclude that an immune response to PSA may be generated in some patients through vaccinia-PSA immunization.

Reviewer: Jon Cartledge

Journal:	Urology
Authors:	Goluboff ET, Shabsigh A, Saidi JA, Weinstein B, Mitra N, Heitjen D, Piazza GA, Pamukcu R, Buttyan R and Olsson CA	Issue:	53(2): 440-445

Title:

Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis

Abstract:
Exisulind is a derivative of the non-steroidal anti-inflammatory drug (NSAID) sulindac that has been shown in vitro to suppress prostate cancer cell lines. The authors induced human prostate cancer cell lines in nude mice. Twenty-one days later one group was fed low dose Exisulind, and another group was fed high dose Exisulind. The authors report a significant reduction in tumour growth in the presence of Exisulind (158%-control, 24%-low dose, 18%-high dose). They conclude that a non-COX inhibitory NSAID has in vivo tumour inhibitory effects.

Reviewer: Jon Cartledge

Journal:	Urology
Authors:	Grado GL, Collins JM, Krieghauser JS, Balch CS, Grado MM, Swanson GP, Larson TR, Wilkes MM and Navickis RJ.	Issue:	1999, 53(1): 2-10

Title:

Salvage brachytherapy for localized prostate cancer after radiotherapy failure

Abstract:
The authors reviewed 64 month follow-up data for 49 patients that had undergone brachytherapy following previous failure of external beam radiotherapy treatment for localised prostate cancer. Of this group, 6 had undergone orchiectomy, 5 anti-androgen therapy and 4 prostatectomy. Previous treatments were considered to have failed because of rising PSA (36), abnormal DRE (8) or local symptoms (2). Recurrence was confirmed by biopsy in all patients. Following brachytherapy disease-specific survival was 89% (3-year) and 79% (5-Year). Biochemical disease free survival was reported at 48% and 34%. The authors conclude that brachytherapy offers a potentially curative salvage for patients that have escaped control following radiotherapy.

Reviewer: Jonathan Cartledge

Journal:	Journal of Urology
Authors:	Adler HL, McCurdy MA, Kattan MW, Timme TL, Scardino PT and Thompson TC	Issue:	1999, 161:182-187

Title:

Elevated levels of circulating interleukin-6 and transforming growth factor b -1 in patients with metastatic prostatic carcinoma

Abstract:
A number of cytokines have been found to be secreted by and influence the growth of prostate cancer cells in culture. In this paper, the authors measured serum levels of IL-6, TNF-a , and GM-CSF in patients with prostate cancer as well as non-cancer controls. Plasma TGF-b1 was only measured in controls and patients with metastatic disease. IL-6 and TGF-b1 both appeared to correlate with tumour burden, as assessed by PSA or clinically evident metastasis, but there appeared to be little correlation with local tumour stage.

Reviewer: Andrew Elves

Journal:	Lancet
Authors:	Dearnaley DP, Khoo VS, Norman AR, Meyer L, Nahum A, Tait D, Yarnold J and Horwich A	Issue:	353: 267-272

Title:

Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial

Abstract:
This randomised controlled study attempted to determine whether conformal radiotherapy has fewer side effects that last beyond 3 months than conventional radiotherapy in the treatment of prostate cancer. Conformal radiotherapy allows irradiation to a smaller volume of tissue by technical improvements in imaging and three-dimensional radiotherapy-planning systems. There were 242 patients eligible and most had T3 disease. Neoadjuvant hormonal therapy was given to 68% in each group: 114 patients received conformal and 111 conventional radiotherapy (64 Gy). Clinical features were equal, although the PSA was higher in the group receiving conventional radiotherapy. The most common and troublesome side effect was proctitis, which usually appeared as rectal bleeding in 56% of the conventional group and 37% of the conformal group. There was no difference in tumour control and these results suggest dose escalation studies are possible.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Hoedemaeker RF, Kranse R, Rietbergen JB, Kruger AE, Schroder FH and van der Kwast TH	Issue:	1999, 85: 145-152

Title:

Evaluation of prostate needle biopsies in a population based-screening study: the impact of borderline lesions

Abstract:
One of the worries of performing a large scale screening study for prostate cancer is the possible detection of a large number of lesions for which no specific diagnosis can be made (e.g. high grade prostatic intraepithelial neoplasia (PIN) or borderline lesions). In the European randomised study of prostate cancer screening (ERSPC), 8763 patients from the Rotterdam arm were screened for prostate cancer by PSA, digital rectal examination and transrectal ultrasound (TRUS). TRUS biopsies were performed on finding a suspicious abnormality. Biopsies were performed on 1,824 from 8,763 men and 384 (4%) had prostate cancer, 12 (0.1%) had prostatic intraepithelial neoplasia and 43 (0.5%) had borderline lesions. Cancer was found on repeat biopsies in 5 patients who had PIN (42%) and 15 patients with borderline lesions (38%). Tumours were similar in those detected on first and second biopsy. Only 3.1% patients had an indication for repeat biopsy indicating that the excess workload from a screening study is unlikely to be significant.

Reviewer: Marc Laniado

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Gleave MM, Goldenberg SL, Bruchovsky N and Rennie P.	Issue:	1998, 1(6): 289-96

Title:

Intermittent androgen suppression for prostate cancer: rationale and clinical experience.

Abstract:
This review explains the rationale for the use of intermittent androgen suppression (IAS) in the treatment of prostate cancer, and examines the argument that IAS can improve quality of life as well as decrease both the side-effects and cost of treatment. Whilst recommendations are made for cessation and re-institution of such therapy, no randomised prospective trials on progression and survival exist to support these views.

Reviewer: James Green

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Polascik TJ, Pearson JD and Partin AW.	Issue:	1998, 1(6): 301-06

Title:

Use of multivariate models to improve prediction of pathological stage for men with clinically localised prostate cancer.

Abstract:
Whilst serum PSA, biopsy Gleason scores and clinical stage all correlate with pathological stage by univariate analysis they are unable to accurately predict pathological stage in an individual patient. This review sets out to persuade the few who remain unconverted that multivariate analysis increases the ability to predict an outcome compared with any single variable. It generously mentions work by other researchers who have shown that the number of positive cores and the percent of cancer on the biopsy are associated with tumour volume and thus stage.

Reviewer: James Green

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Guinan P, Stewart AK, Fremgen AM and Menck HR.	Issue:	1998, 1(6): 314-20

Title:

Patterns of care for metastatic carcinoma of the prostate gland: results of the American College of Surgeons' patient care evaluation study.

Abstract:
Data on 14,716 patients with newly diagnosed prostate cancer from 730 hospitals in 1984 and from 23,214 patients from 1,035 hospitals in 1990 were collated. Over this time period there was a veritable explosion in the use of serum PSA testing from 6.3% to 74.8%. The number of cancers diagnosed on transurethral resection and perineal biopsy decreased and the proportion of Stage IV disease decreased from 25.3% to 21.2%. Also of interest, treatment by orchidectomy alone increased from 31.8% to 40.7% and exogenous hormone therapy alone decreased from 22.3% to 14.9%.

Reviewer: James Green

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Roth HJ, Stewart SC and Brawer MK.	Issue:	1998, 1(6): 327-31

Title:

A comparison of three free and total PSA assays.

Abstract:
The problems with referencing total serum PSA have now been compounded by variations in manufacturers' assays for free serum PSA. This study showed that The ACS: 180 assay produced by the sponsors of the study had greater concordance with the Hybritech assay than a competitors product. This study quite rightly underscores the requirement of laboratories and manufacturers to define appropriate cut-offs and have excellent quality control to keep standardisation tight. Further research into inter-assay standardisation of all the assays on the market would obviously benefit patients although consistent use of an established assay would be a less tortuous solution for clinicians.

Reviewer: James Green

Journal:	Urology
Authors:	Weinrich M, Jacobsen SJ, Weinrich SP, Moul JW, Oesterling JE, Jacobson D and Wise R.	Issue:	1998, 52(6): 967-973

Title:

Reference ranges for serum prostate-specific antigen in black and white men without cancer

Abstract:
The authors collected PSA results by PSA and digital rectal examination (DRE) for carcinoma of the prostate, from 1,319 men screened by a primary care physician. This data was used to produce age and race specific reference ranges for men without cancer (on the basis of negative DRE). The authors report that PSA increases by 3.3% per year in older men without cancer. They produce reference ranges for black men of 0-1.9 ng/ml (age 40-49), 0-3.8 ng/ml (age 50-59), 0-5.7 ng/ml (age 60-69) and for white men 0-2.7 ng/ml ( age 50-59) and 0-4.9 ng/ml (age 60-69). They conclude that reference ranges should take into account the ethnic population from which they are drawn.

Reviewer: Jonathan Cartledge

Journal:	Journal of Urology
Authors:	Oefelein MG	Issue:	1998, 160: 1685-1688

Title:

Time to normalisation of serum testosterone after 3 month lutenising hormone releasing agonist administered in the neoadjuvant setting: implications for dosing schedule and neoadjuvant study considerations.

Abstract:
This small series of experiments investigates the time course to normalisation of testosterone and biological duration of androgen suppression and clinical symptoms after a single 3-month formulation of LHRH agonist in the neoadjuvant setting. After administration of a single 3-month LHRH agonist the median duration of castrate level of testosterone was 6 months while the median duration of hypogonadal symptoms was 13.6 months. While these preliminary observations may have implications for neoadjuvant dosing schedules of LHRH agonists among patients receiving radical treatment they also have important implications for the justification of intermittent hormone therapy.

Reviewer: Andrew Elves

Journal:	Urology
Authors:	Klotz L and Herschorn S.	Issue:	1998, 52 (4): 537-542

Title:

Early experience with intra-operative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy.

Abstract:
The authors report the application of cavernous nerve stimulation and monitoring for penile tumescence during radical prostatectomy in patients with T1c or T2a-c, Gleason <8 prostate cancer, PSA<15 ng/ml, and no pre-operative adjuvant treatment. Nerve stimulation was performed in 23 patients. If a tumescent response was noted the pedicle was dissected medial to the site of stimulation, therefore presumably preserving the cavernous complex. Pre-operatively, 19 patients had normal erectile function. Of these, 16 demonstrated a tumescent response intra-operatively. One year post-operatively, 5 of 16 had full erections, 11 of 16 had partial erections and 3 of 19 had no erections. The authors do not report an overall rate for erectile potency, but from the data presented 21% (5/23) had normal erections and 48% (11/23) partial erections. The authors conclude that this procedure can aid the surgeon in identifying the cavernous nerve at radical prostatectomy.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Kapoor DA, Klimberg IW, Malek GH, Wegenke JD, Cox CE, Patterson AL, Graham E, Echols RM, Whalen E and Kowalsky SF.	Issue:	1998, 52 (4): 552-558

Title:

Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy.

Abstract:
This prospective randomised double blind placebo controlled trial compared the administration of 500 mg ciprofloxacin or placebo before transrectal needle biopsy of the prostate. Urine was examined on day 2-6 and day 9-15 post procedure for bacteriuria. Out of 537 patients, 269 received ciprofloxacin and 268 received placebo. A hundred patients were excluded from the analysis due to insufficient culture data. Bacteriuria was recorded in 3% of patients on ciprofloxacin and 8% on placebo. Symptomatic UTI was recorded in 3% of patients on ciprofloxacin and 5% on placebo. In this group, 4 patients were admitted for treatment of septicaemia. The authors conclude that single dose oral ciprofloxacin reduced bacteriuria after transrectal biopsy of the prostate and established that the rate of bacturia is 8% for this procedure.

Reviewer: Jonathan Cartledge

Journal:	New England Journal of Medicine
Authors:	Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ and Lowe BA	Issue:	1998, 339(15): 1036-42

Title:

Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.

Abstract:
The current randomised-controlled study by the same authors compared orchiectomy with flutamide or placebo in 1387 men with previously untreated Tx Nx M1 prostate cancer. Crawford et al. (NEJM 1989, 321: 1420) have previously reported a 25% benefit of combined androgen blockade over LH-RH agonists alone. Their findings have been used as evidence supporting combined androgen blockade in the treatment of prostate cancer of patients with newly diagnosed Tx Nx M1 disease. The maximum benefit was seen in younger patients with good performance status only on retrospective subgroup examination. Also, the LH-RH agonist in that study needed to be administered daily rendering compliance a problem, particularly in comparison to castration. Of the 1387 patients, 700 were assigned to the flutamide group and 687 to the placebo group. Median follow up was 49 months in the placebo group and 50 months in the flutamide group. Median survival in patients with good performance status was 51 months in the placebo group and 52 months in the flutamide group. Median survival in patients with poor performance status was 28 months in patients on placebo and 29 months in patients with flutamide. Diarrhoea occurred in 6% of patients on flutamide compared to 3% on placebo and anaemia was a problem in 9% of patients on flutamide compared to 5% of patients on placebo. This study indicates that even when patients are stratified by performance status a priori, there is no survival benefit to combined androgen blockade over castration alone in patients with newly diagnosed metastatic prostate cancer. This study also suggests that reduced PSA was not a surrogate marker for survival, raising concern about studies that compare treatment benefit by PSA responses alone.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Ragde H, Elgamal AA, Snow PB, Brandt J, Bartolucci AA, Nadir BS and Korb LJ.	Issue:	1998, 83(5): 989-1001

Title:

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma.

Abstract:
In 1995, 34% of all patients diagnosed with T1-2 Nx M0 prostate cancer in the USA were treated by radical prostatectomy, 26% by external beam radiotherapy and 2% by brachytherapy (data from the national cancer database in the USA). In this study, a total of 152 consecutive patients with T1-3 Nx M0 prostate cancer were treated by transrectal ultrasound guided 125I brachytherapy in Washington between 1987 and 1988. At 10 years, overall survival was 65%, disease specific survival 98% and 66% of patients had disease specific survival with PSA < 0.5. The time required to reach an average PSA < 0.5 ng/ml was 4 years. Positive biopsies were obtained in 23 of 85 tested after an average of 55 months. The better survival with external beam radiotherapy combined with brachytherapy in patients with poorer pre-treatment prognostic factors was significant and suggests that future trials should combine brachytherapy with external beam radiotherapy.

Reviewer: Marc Laniado

Journal:	Journal of the American Medical Association
Authors:	D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A.	Issue:	1998, 280(11): 969-74

Title:

Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer.

Abstract:
This is a retrospective cohort study on outcomes in 1,872 men treated for localised prostate cancer by radical prostatectomy, radical radiotherapy and brachytherapy (103Pd) with or without endocrine therapy. The direct comparison with brachytherapy has not been performed before and therefore this is an important study. PSA failure was used as a surrogate marker for survival so, in patients having radiotherapy, 3 consecutive rising PSA values taken 3 months apart were necessary. For men at low risk (T1c or T2a, PSA < 10, Gleason score < 7) the study demonstrated no significant difference in survival (relative risk) compared to radical prostatectomy although the 95% confidence intervals were wide (RT 0.5 to 2.7, brachytherapy plus implant 0.1 to 1.9, brachytherapy alone 0.3 to 3.6). In high-risk patients (PSA > 20, Gleason score > 7), the relative risks of PSA failure were 3.0 (CI 1.5 to 6.1) for brachytherapy compared with radical prostatectomy. The addition of endocrine therapy to brachytherapy reduced the PSA failure rates, but endocrine treatment alone may be just as effective and was not tested in this study. The looser criteria for PSA failure in patients with radiotherapy may underestimate the true biochemical failure rate and the potentially better outcome by radical prostatectomy. Also, the brachytherapy group had more low-grade tumours that may result in an overestimate of the treatment benefit of brachytherapy. The results reported in this study would suggest that there should be some temperance with which clinicians are rushing into new treatments such as brachytherapy.

Reviewer: Marc Laniado

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Moul JW, Mooneyhan RM, Kao T-C, Mcloed DG and Creuss DF.	Issue:	1998, 1(5): 243-49

Title:

Preoperative and operative factors to predict incontinence, impotence and stricture after radical prostatectomy.

Abstract:
One of the criticisms of peer review publications and multivariate analysis of research papers is that they are biased by articles finding positive results and correlations. This article is refreshing since it was published despite finding no factor (either demographic, preoperative, operative or tumour associated) that, on multivariate analysis, was predictive for any of the above complications of radical prostatectomy. Urinary incontinence, however, was predicted by pathological stage on univariate analysis. Of 458 eligible patients, 374 (81.7%) returned self-reporting quality of life questionnaires. Of these, 72.2% were not completely continent, 87.4% were impotent and 25.9% had bladder neck stricture. Interestingly, in spite of this morbidity, the majority of patients (75.1%) would chose surgical treatment again.

Reviewer: James Green

Journal:	Urology
Authors:	Kilic S, Yalcinkaya S, Guntekin E, Kukul E, Deger N and Sevuk M.	Issue:	1998, 52 (3): 470-473

Title:

Determination of the site of metabolism of total, free and complexed prostate-specific antigen

Abstract:
The authors took blood samples from the infrarenal, infrahepatic and suprahepatic inferior vena cava, renal vein, hepatic vein, superior vena cava, pulmonary artery and femoral artery of male patients over 50 years of age undergoing left and right heart catheterisation. They measured free PSA, total PSA and complexed PSA from each sample to determine the site of metabolism of each. The authors conclude that f-PSA and t-PSA are released from the prostate but that the prostate does not play a role in c-PSA production. They also report that all three forms of PSA are probably metabolised in the liver and only f-PSA is metabolised in the kidneys. The lungs have no effect on levels of any form of measured PSA.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Jacobsen SJ, Bergstralh EJ, Katusic SK, Guess HA, Darby CH, Silverstein MD, Oesterling JE and Lieber MM.	Issue:	1998, 52 (2): 173-179

Title:

Screening digital rectal examination and prostate cancer mortality: a population-based case control study.

Abstract:
The authors identified all deaths due to prostate cancer from 1976-1991 and reviewed their primary care and hospital case records along with age matched controls. The dates of digital rectal examination (DRE) in the 10 years preceding death were recorded. Out of a total of 173 prostate cancer deaths, the average age of death was 79 years. They found that control subjects were more likely than prostate cancer patients to have had a DRE in the prior 10 years, as were those men with a college education, and men over 70 years of age. They conclude that screening by DRE was much less common in men who had died of prostate cancer, and, if results indicate a causal mechanism, they suggest screening may have prevented 50% to 70% of deaths in the pre PSA era.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Stevens RA, Mikat-Stevens M, Flanigan R, Waters WB, Furry P, Sheikh T, Frey K, Olsen M and Kleinman B.	Issue:	1998, 52 (2): 213-218

Title:

Does the choice of anaesthetic technique affect the recovery of bowel function after radical prostatectomy?

Abstract:
The authors randomised 40 men undergoing radical prostatectomy to either receive general anaesthetic (GA) with muscle relaxation and mechanical ventilation or thoracic epidural anaesthesia with a light GA and spontaneous respiration. Post-operatively, all patients were given ketorolac +/- morphine in the recovery room. GA patients had morphine patient controlled anaesthesia until the return of bowel sounds, then oral non-steroidal anti-inflammatory drugs (NSAIDS). Epidural patients were given a single dose of epidural opiate in recovery then intravenous morphine as required until return of bowel sounds and then oral NSAIDS. The epidural group had less blood loss, lower post-operative pain scores in recovery and less morphine requirement in the 48 hours after surgery than GA patients, and their bowel function also returned significantly quicker (36 vs. 48 hours). The authors concluded that epidural anaesthesia with light GA is an effective alternative to GA and offers the advantage of earlier return of bowel function.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Smith DC, Redman BG, Flaherty LE, Li L, Strawderman M and Pienta KJ.	Issue:	1998, 52 (2): 257-260

Title:

A phase II trial of oral diethylstilboestrol as a second-line hormonal agent in advanced prostate cancer.

Abstract:
This study reports a phase II trial evaluating diethylstilboestrol (1 mg /day) in patients with hormone-refractory prostate cancer which was defined as a rising PSA on stopping flutamide, prior to cessation of LHRH agonists. Of 21 patients, 9 achieved a response (50% fall in PSA), and their estimated survival was 63% at 2 years. The patient group was diverse with 48% having only local disease, and 52% metastatic disease. The authors conclude that these early results are promising but further studies are necessary.

Reviewer: Jonathan Cartledge

Journal:	British Journal of Urology
Authors:	Lein M, Koenig F, Jung K, McGovern FJ, Skates SJ, Schnorr D and Loening SA.	Issue:	1998, 82: 231-236

Title:

The percentage of free prostate specific antigen is an age-independent tumour marker for prostate cancer: establishment of reference ranges in a large population of healthy men.

Abstract:
This paper, a joint US and German collaboration, provides further useful information on the use of free to total PSA ratios. Although the results of their findings are not related to the presence of prostate cancer in any of the men studied (>1100), they do demonstrate that the free to total PSA ratio does not alter over the decades. A cut off for the ratio of 12.5% is selected, as that represents the 5th centile.

Reviewer: Jonathan Glass

Journal:	British Journal of Urology
Authors:	Fitzpatrick P, Corcoran N and Fitzpatrick JM.	Issue:	1998, 82: 43-48

Title:

Prostate cancer: how aware is the public?

Abstract:
It may be difficult to imagine but it would appear that there are some people in the world who have not heard of prostate cancer. The authors of this paper went out into the community and found that having a female partner, being married, having seen a doctor about urinary tract symptoms, and being in a higher socioeconomic group were associated with knowledge of prostate cancer. Improving cancer awareness in the lower socio-economic groups may be important in identifying the disease when it can be cured.

Reviewer: Jonathan Glass

Journal:	Urology
Authors:	Bjork T, Ljungberg B, Piironen T, Abrahamsson P, Pettersson K, Cockett ATK and Lilja H.	Issue:	1998, 51 (1): 57-61.

Title:

Rapid exponential elimination of free PSA contrasts the slow, capacity-limited elimination of PSA complexed to alpha1-antichymotrypsin from serum.

Abstract:
The authors measured free and protein bound PSA levels in 10 patients undergoing radical retropubic prostatectomy preoperatively and in the immediate post operative period. All patients had no evidence of distant mets or local lymph node disease. They demonstrate that manipulation of the prostate during surgery leads to an increase in free-PSA of 3 - 28X. Post operatively free PSA levels reduced exponentially with a half life of 0.81 hours. Protein bound PSA reduced by 20 - 49% immediately post op, with further elimination being non exponential at a rate of 0.8 ng/day.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	MV Hansen and A Zdanowski	Issue:	1997, 80 (5): 787-792.

Title:

The agreement among urological experts on the diagnostic management of patients with common urological problems.

Abstract:
Thirty three urologists were asked to investigate and treat 53 simulated urological conditions. The probability of the urologists using a certain test in a certain patient was recorded and the cost implications evaluated. Most consistency was seen treating stone patients, then bladder cancer, prostate cancer and lastly BPH. These were all university based consultants.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Optenberg SA, Clark JY, Brawer MK, Thompson IM, Stein CR and Friedrichs P.	Issue:	1997, 50 (5): 655-672.

Title:

Development of a decision-making tool to predict risk of prostate cancer: The cancer of the prostate risk index (CAPRI) test.

Abstract:
The authors aim was to produce a reliable way for clinicians to predict the risk of an individual patient having cancer on testicular biopsy. They reviewed the pathology records of patients that had undergone prostate biopsy in one centre over a 5 year period and recorded histology, PSA, DRE findings, race and age. An external control population was taken from another centre. Using multiple logistic regression techniques they constructed models relating PSA to cancer risk, and applied variables of race, DRE findings and age to construct a patient specific risk of cancer. Findings are plotted as two charts. One relates age to probability of cancer for blacks or whites with and without an abnormal DRE, the second plots risk of cancer for a specific age and PSA. The authors conclude that PSA, DRE and age all contribute significantly and independently to the prediction of prostate cancer. They have produced a software programme to calculate the individual risk for a patient (CAPRI).

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Mikolajczyk SD, Grauer LS, Millar LS, Hill TM, Kumar A, Rittenhouse HG, Wolfert RL and Saedi MS.	Issue:	1997, 50 (5): 710-713.

Title:

A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum.

Abstract:
The authors used a western blot analysis and chromatography techniques to examine serum and seminal fluid from patients with known prostate cancer to try and determine the nature of free PSA within serum. They demonstrated that clipped or degraded PSA, commonly present in seminal fluid, was very rarely present in serum. They report that about 25% of free PSA is zymogen, a precursor PSA, pPSA, which is inactive and does not bind with serum proteins to form complexed PSA. They suggest that before pPSA is useful in the assessment of individual patients a more sensitive immunoassay will have to be developed.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Chun TY, Martin S and Lepot H.	Issue:	1997, 50 (5): 727-732.

Title:

Pre-operative Recombinant Human Erythropoietin Injection versus Pre-operative Autologous Blood Donation in patients undergoing Radical Retropubic Prostatectomy.

Abstract:
To try and reduce the costs and risks of allogenic blood transfusion for patients undergoing RPP the authors prospectively compared the use of pre-operative autologous blood donation (PAD) with pre-operative recombinant human erythropoietin donation. Patients were randomised to receive erythropoietin 14 and 7 days pre-operatively if their haematocrit was lower than 46% (increased risk of stroke for HCT >46%) or give 1 unit of blood every 4 days pre-operatively, upto 3 units. Transfusion was only given according to an established protocol. Half the patients receiving erythropoietin did not require a second injection because their HCT reached 46% with a single dose. 80% of PAD patients received transfusion of their own blood. In both groups 9.6% of patients required allogenic transfusion. The authors conclude that pre-operative erythropoietin is a safe alternative to autologous transfusion.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Norberg M, Egevad L, Holmberg L, Sparen P, Norlen BJ and Busch C.	Issue:	1997, 50 (4): 562-566.

Title:

The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer

Abstract:
The aim of the authors was to compare the sensitivity of a sextant prostatic biopsy protocol with a more extensive procedure for detecting prostate cancer. 512 consecutive patients underwent TRUS & biopsy. Each patient had 8-10 biopsies in standardized sites plus biopsies targeted at hypo or hyperechoic regions. This procedure was defined as the reference regime and the detection rate of other protocols, calculated by excluding biopsy samples from analysis to create a 6 biopsy regime, compared with it. The reference regime detected 276 cancers. Sensitivity of standard sextant biopsies was 85%, increasing to 93% by adding targeted biopsies. The authors conclude that although 8-10 biopsies plus targeting may still miss cancers, a sextant biopsy protocol will miss 15% of these tumours.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	O'Dowd GJ, Veltri WR, Orozco R, Miller MC and Oesterling JE	Issue:	1997, 158: 687-698.

Title:

Update on the appropriate staging evaluation for newly diagnosed prostate cancer.

Abstract:
With positive margin rates following radical prostatectomy of between 30 and 70%, the need to establish more accurate methods of clinical staging is apparent. The authors provide a review of 142 articles identified from a Medline database search, which evaluate the pre-operative accuracy of digital rectal examination, prostate-specific antigen, acid hosphatase, systematic biopsy parameters, seminal vesicle biopsy, and various imaging techniques and pelvic lymphadenectomy versus pathological staging results. Accurate pre-operative staging is best achieved employing several stastistically independent staging parameters. The most accurate decision support tools for clinical staging combined digital rectal examination (T stage), systematic biopsy parameters (including gleason score) and prostate-specific antigen.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Khoudary KP, Dewoll WC, Brunning CO and Mergentaler A.	Issue:	1997, 50 (3): 395-399.

Title:

Immediate sexual rehabilitation by simultaneous placement of penile prosthesis in patients undergoing radical prostatectomy: Initial results in 50 patients.

Abstract:
Between 1993 and 1996 all men undergoing radical prostatectomy were counselled pre-operatively and offered treatment for impotence post-operatively. This series retrospectively reports 50 men who opted for non-nerve sparing radical prostatectomy and simultaneous penile prosthesis. This group was compared with 72 men undergoing radical prostatectomy alone during the same time period. Mean operative time was extended by 120 mins to insert a prosthesis. There was no significant difference in operative complications, length of hospital stay or analgesic requirement. Four prosthesis were revised due to bending, none were infected after 1.7 years follow up. At 12 weeks post-operatively 96 % of patients were sexually active. They conclude that simultaneous placement of prosthesis allows an uncomplicated return to sexual function. There is however no record of whether patients having radical prostatectomy alone had a nerve sparing procedure or comparison made of post-operative potency between the 2 groups.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Schellhammer P, Shardi R, Block NL, Soloway MS, Venner PM, Lynn Patterson A, Sarosdy MF, Vogelzang NJ, Jones Schellenger J and Kolvenbag for the Casodex Combination Study Group	Issue:	1997, 50 (3): 350-357.

Title:

Clinical benefits Of Biclutamide compared with Flutamide in combined Androgen Blockade for patients with advanced prostatic carcinoma: Final report of a double-blind, randomized, multicenter trial.

Abstract:
A large multicentre randomized trial to compare LHRH analogue plus biclutamide or flutamide in patients with metastatic prostate cancer (Stage D2). Trial end points were time to clinical progression and time to death, with a median follow up of 160 weeks. They report a progression rate of 71% (biclutamide) vs. 72% (flutamide) and an overall death rate of 55%. For patients on LHRH plus biclutamide, mortality was 53% and 57% for flutamide (p=0.15). Side effects included hot flushes in 53% of all patients and diarrhoea in 26% of those on flutamide compared to 12 % on biclutamide (p<0.001). They conclude that biclutamide plus LHRH analogue was well tolerated with a trend towards longer survival compared to flutamide plus LHRH analogue.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Pacelli A and Bostwick D.	Issue:	1997, 50 (3): 355-359.

Title:

Clinical significance of high-grade Prostatic Intraepithelial Neoplasia in Transurethral Resection Specimens.

Abstract:
The aim of this study was to determine the incidence and significance of high grade PIN in TUR prostate specimens. The histology from 698 consecutive patients undergoing TURP was examined (pre-operatively diagnosed cancer excluded). High grade PIN was found in 29 cases (4.2%), 16 of 570 with BPH alone and 13 of 128 with BPH and incidental adenocarcinoma. PIN was found only in a single chip in the BPH alone group. Follow up was available for 14/16 PIN + BPH patients, three subsequently diagnosed with carcinoma prostate, at 3,5 and 7 years post initial resection. They suggest that if PIN is found all tissue should be examined for coexisting carcinoma and suggest regular follow-up at 3 month intervals for 2 years with annual follow up thereafter.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Scates DK, Muir GH, Venitt S, Carmichael PL.	Issue:	1997, 80 (2): 263-268.

Title:

Detection of telomerase activity in human prostate: a diagnostic marker for prostate cancer.

Abstract:
Is telomerase a possible predictive marker in identifying which patients with BPH may develop prostate cancer? This study showed telomerase activity to be present in 8 of 9 patients with CaP, 6 of 16 patients with BPH and none of 11 normal prostates. Other studies have not identified telomerase activity in prostates with BPH but if the results of this study are repeated can its presence be used as a marker of PIN or early prostate cancer missed by biopsy?

Reviewer: Mark Feneley

Journal:	New England Journal of Medicine
Authors:	Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M (on behalf of the EORTC)	Issue:	1997, 337: 295-300.

Title:

Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and Goserelin.

Abstract:
This large European study randomised 415 patients with locally advanced prostate cancer to radiotherapy alone or radiotherapy and androgen ablation with an LHRH analogue. 401 patients were available for analysis with a mean follow up of 45 months. 5 year survival was 79% versus 62% in favour of treatment with adjuvant hormonal therapy, and 85% versus 48% disease free survival in those patients still alive. Adjuvant hormonal therapy clearly hs a role in this setting but what contribution is the radiotherapy having?

Reviewer: Mark Feneley

Journal:	Journal of the American Medical Association
Authors:	Krongrad A, Lai H and Lai S .	Issue:	1997, 278: 44-46.

Title:

Survival after radical prostatectomy.

Abstract:
This study provides data on survival after radical prostatectomy which can be applied broadly and is not only applicable for patients attending tumour centres. It is population based and uses retrospective data. Estimates of 10-year survival vary from about 80% for well-differentiated cancer to 70% for patients with moderately differentiated cancer. The data uses pathological staging and not clinical staging and survival estimates should not be compared with other modalities of treatment like radiotherapy or watchful waiting for which pathological data are not usually available.

Reviewer: Mark Feneley

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Nakashima J, Imai Y, Tachibana M, Baba S, Hiramatsu K, Murai M.	Issue:	1997, 80: 237-241.

Title:

Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging.

Abstract:
This is a retrospective study using MRI to demonstrate the proportional change in size of areas of cancer and BPH following endocrine therapy. The cancer decreases in size by about three-quarters, BPH areas also decrease by about 17% but there was considerable variability.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Douglas TH, Morgan TO, McLeod DG, Moul JW, Murphy GP, Barren GP, III, Sesterhenn IA, Mostofi FK.	Issue:	1997, 80:107-114.

Title:

Comparison of serum prostate specific membrane antigen, prostate specific antigen, and free prostate specific antigen levels in radical prostatectomy patients.

Abstract:
This study used banked serum from patients and shows that for patients selected for radical prostatectomy each test is poor in discriminating between localised disease or not. The best was total PSA. If this was less than 5.1 the likelihood ratio of having negative surgical margins was 3.8 ie it increased the probability of having negative surgical margins from 63% to 83% in this series. When the tests were positive, they changed the possibility of positive surgical margins very little. Better tests are needed.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Facher EA, Becich MJ, Deka A, Law JC.	Issue:	1997, 79: 2424-2429.

Title:

Association between human cancer and two polymorphisms occurring together in the p21Waf1/Cip1 cyclin-dependent kinase inhibitor gene.

Abstract:
This study looked at polymorphisms of the cyclin-dependent kinase inhibitor gene p21Waf1/Cip1, which is important in signalling cellular growth arrest. P21 protein is induced by p53 in the presence of cell damage and is important in mediating p53-induced G1 arrest. This study examined the incidence of two polymorphisms of the gene and found that they occurred in about 20% of prostate cancer compared to 10% of controls. The latter were not perfect and there is a need for further study.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Facher EA, Becich MJ, Deka A, Law JC.	Issue:	1997, 79: 2424-2429.

Title:

Association between human cancer and two polymorphisms occurring together in the p21Waf1/Cip1 cyclin-dependent kinase inhibitor gene.

Abstract:
This study looked at polymorphisms of the cyclin-dependent kinase inhibitor gene p21Waf1/Cip1, which is important in signalling cellular growth arrest. P21 protein is induced by p53 in the presence of cell damage and is important in mediating p53-induced G1 arrest. This study examined the incidence of two polymorphisms of the gene and found that they occurred in about 20% of prostate cancer compared to 10% of controls. The latter were not perfect and there is a need for further study.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Ennis RD, Katz AE, De Vries GM, Heitjan DF, O'Toole KM, Rubin M, Buttyan R, Benson MC, Schiff PB.	Issue:	1997, 79: 2402-2408.

Title:

Detection of circulating prostate carcinoma cells via an enhanced reverse transcriptase-polymerase chain reaction assay in patients with early stage prostate carcinoma. Independence from other pretreatment characteristics.

Abstract:
This study shows that reverse transcriptase-polymerase chain reaction (RT-PCR) for PSA and serum PSA prior to surgery are good predictors of pathological stage of the radical prostatectomy specimen. The differences between RT-PCR PSA and serum PSA were not clinically relevant and it remains to be proven whether selecting patients on the basis of RT-PCR will help identify patients for surgery better than current staging modalities.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Powell CR, Huisman TK, Riffenburgh RH, Saunders EL, Bethel KJ and Johnstone PAS.	Issue:	1997, 157: 1754-1759.

Title:

Outcome for surgically staged localized prostate cancer treated with external beam radiation therapy.

Abstract:
The authors performed a retrospective analysis of overall, cause-specific and disease-free survival at 10 years of 129 patients who had received external beam radiation therapy after negative staging lymphadenectomy. Disease-free survival was based upon a normal digital rectal examination, absence of symptoms suspicious of metastasis and normal PSA. Actuarial overall-survival was 63.7% at 10 years and 49.6% at 15 years. Cause-specific survival at 10 and 15 years was 84.5% and 80% respectively. Disease-free survival was 54.5 and 32.4% respectively. This study confirms the findings of other smaller series and would support the use of surgical staging as a means of increasing the prognostic information available upon which to discuss treatment options with patients.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Schellhammer PF, Venner P, Haas GP, Small EJ, Nieh PT, Seabaugh DR, Patterson AL, Klein E, Wajsman Z, Furr B, Chen Y and Kolvenbag GJCM..	Issue:	1997, 157: 1731-1735.

Title:

Prostate-specific antigen decreases after withdrawal of anti-androgen therapy bicalutamide or flutamide in patients receiving androgen blockade.

Abstract:
The anti-androgen withdrawal syndrome has been observed both for flutamide and bicalutamide in a number of case reports and small retrospective cohort studies. This paper evaluates the effects of withdrawal of double-blinded anti-androgen therapy with flutamide (8 patients) or bicalutamide (14 patients) for clinical progression or increasing PSA concentration in patients receiving maximal androgen blockade for advanced prostate cancer. All patents had clinical disease progression or rising PSA and had received maximal androgen blockade for a minimum of 140 days. In 4 (50%) patients receiving flutamide, and 4 (29%) patients receiving bicalutamide PSA decreased by 50% or more. PSA response occurred within days for those patients treated with flutamide while the response occurred over 4-8 weeks in the bicalutamide treated patients. Withdrawal of both flutamide and bicalutamide in patients with advanced prostate cancer demonstrating clinical progression or rising PSA may result in a PSA response, but the clinical significance of this is unknown. The time to PSA response is longer with bicalutamide.

Reviewer: Mark Feneley

Journal:	Journal of the American Medical Association
Authors:	Carter HB, Epstein LI, Chan DW, Fozard JD and Pearson JD.	Issue:	1997, 277: 1456-60.

Title:

Recommended prostate-specific antigen testing intervals for the detection of curable prostate cancer.

Abstract:
This is an interesting study albeit complicated. The authors identified a cohort of patients with PSA values less than 2, between 2.1 and 4, between 4 and 5 and greater than 5 ng/ml. They showed that patients having normal digital rectal examination and serum PSA less than 2 were unlikely to develop higher PSA values that would place them in a category associated with non-curable prostate cancer within 2 or 4 years. Annual testing for these patients was therefore unnecessary. This would save large sums of money as about 70% of patients have PSA values less than 2 and so annual PSA tests would not be necessary. PSA conversion to a range at which cancers are likely to be curable (4.1-5.0 ng/mL) was common when the baseline PSA level was between 2.1 and 3.0 ng/mL (27%) or 3.1 and 4.0 ng/mL (36%). Such patients should have PSA tests more frequently.

Reviewer: Mark Feneley

Journal:	Journal of the American Medical Association
Authors:	Partin AW, Kattan MW, Subong ENP, Walsh PC, Wojno KJ, Oesterling JE, Scardino PT and Pearson JD.	Issue:	1997, 277: 1445-51.

Title:

Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer.

Abstract:
This paper provides probability values on the likelihood of localised disease for patients undergoing radical prostatectomy. Each probability is given with its 95% confidence interval and as such is an update on the original 'Partin' tables. The report shows that for most levels of PSA, Gleason score and TNM stage, the odds of having localised disease are not good – there is still considerable uncertainty. In most cases, the odds are at least one in four of not having localised disease. There is no mention of whether follow-up data on survival has been incorporated into the tables. Clearly, this information would be very helpful. The tables should be useful for readers looking for odds to quote patients before radical treatment for prostate cancer.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Shrader-Bogen CL, Kjellberg JL, McPherson CP and Murray CL.	Issue:	1997, 79: 1977-1986.

Title:

Quality of life and treatment outcomes: prostate carcinoma patients' perspectives after prostatectomy or radiation therapy.

Abstract:
There is poor information regarding differences in quality of life and side effects after radical prostatectomy or radical radiotherapy for prostate cancer. This study compared patients' self-reported quality of life and side effects 1 to 5 years after radical radiotherapy or radical prostatectomy using a validated questionnaire. Two hundred and seventy four men completed the questionnaires successfully. In the radical prostatectomy group (48%), there was more erectile dysfunction and urinary dysfunction than the radical radiotherapy group (52%) in which there was more bowel disturbance. This study shows that men undergoing treatment for clinically localised prostate cancer continue to experience difficulty long after treatment.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Gohji K, Nomi M, Egawa S, Morisue K, Takenaka A, Okamoto M, Ohori M and Fujii A.	Issue:	1997, 79: 1969-1976.

Title:

Detection of prostate carcinoma using prostate-specific antigen, its density, and the density of the transition zone in Japanese men with intermediate serum prostate-specific antigen concentrations.

Abstract:
In Japanese patients with PSA values between 2.1 and 10, it can be as difficult to determine whether further biopsies should be taken and whether patients may have malignancy. This study using 268 archival tissue specimens shows that PSA density can improve the predictive value of the test, but at the same time there will be some reduction in the number of tumours detected. A PSA density of 0.18 ng/ml/ml gave a sensitivity of 70% and specificity of 67%, which translated to a positive likelihood ratio of 2.1 and negative likelihood ratio of 2.2. As 11% of 287 patients had positive biopsies, the prior probability of a patient having prostate cancer on a biopsy changed from 11% to 20% for a positive result and the chance of not having cancer from 89% to 95% for a negative result. PSA density did not appear to be much better than serum PSA alone. PSA density of the transition zone was not better either.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Schmid HP, Maibach R, Bernhard J, Hering F, Hanselmann S, Gusset H, Morant R, Pestalozzi D and Castiglione M.	Issue:	1997, 79: 1703-1709.

Title:

A phase II study of oral idarubicin as a treatment for metastatic hormone-refractory prostate carcinoma with special focus on prostate-specific antigen doubling time. Swiss Group for Clinical Cancer Research, Berne, Switzerland.

Abstract:
There is an urgent need to find effective treatments in patients with hormone relapsed prostate cancer. This phase 2 clinical trial of oral idarubicin in 30 patients was disappointing as few patients responded, although there was minimal toxicity. The search goes on.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Neugut AI, Ahsan H, Robinson E and Ennis RD.	Issue:	1997, 79:1600-1604.

Title:

Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma.

Abstract:
This study from the Surveillance, Epidemiology and End Results Program (SEER) group shows that the risk of bladder cancer after radiotherapy for prostate cancer increases by a factor 1.5 (95% confidence interval 1.1 to 2.0) after 8 years. As the risk per person-year of a bladder cancer is 0.19% and it increases to only 0.26%, it is probably not clinically relevant.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Zagars GK, Pollack A and von Eschenbach AC.	Issue:	1997, 79: 1370-1380.

Title:

Prognostic factors for clinically localized prostate carcinoma: analysis of 938 patients irradiated in the prostate-specific antigen era.

Abstract:
Many studies on prognostic factors come from radical prostatectomy specimen series and their analyses. This study uses clinical stage in patients receiving radical radiotherapy for prostate cancer (T1 to 4, NX, M0) as their only treatment to determine the relative roles of PSA, T stage and Gleason score. Pre-treatment PSA was most important in predicting further rises in PSA or local recurrence whereas T classification was of value in predicting metastatic relapse. The authors formulated a 6-tier classification system with different relapse rates. Unfavourable categories included patients with PSA greater than 20 or patients with tumours of Gleason score 8 to 10 with PSA values between 10 and 20 in whom the relapse rate was 88%.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Hrouda D, Muir GH and Dalgleish AG.	Issue:	1997, 79: 307-316.

Title:

The role of immunotherapy for urological tumours

Abstract:
This paper reviews the use and potential of immunotherapy in bladder, renal and prostate cancers. BCG is the only intravesical therapy which has been shown to reduce disease progression in patients with superficial bladder cancer and remains the most effective example of immunotherapy to date. Interleukin-2 is the current gold standard for advanced renal cell carcinoma, however only 7% of patients having complete regression with this treatment. A number of new immunotherapy approaches such as tumour vaccines are entering clinical trials.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Iversen P, Rasmussen F, Asmussen C, Christensen IJ, Eickhoff J, Klarskov P, Larsen E, Mogensen P, Mommsen S and Rosenkilde P.	Issue:	1997, 157: 929-934.

Title:

Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer: DAPROCA study 9002. Danish Prostatic Cancer Group.

Abstract:
The authors present the findings of a prospective randomised double blind study comparing the effect of 560mg estramustine phosphate daily as a supplement to standard palliative therapy (anti-androgen therapy excluded) against placebo in 131 patients with progressing metastatic hormone refractory prostatic carcinoma of the prostate. End points were clinical progression and death. Adverse effects, changes in PSA and subjective response were also assessed. While diarrhoea and breast tenderness/gynaecomastia were more frequent among the treatment group no significant differences were observed in the end points. Differences in survival and subjective response favoured estramustine phosphate, but were not significant. Any reduction in PSA at 1 month correlated significantly with survival. The authors conclude that there may exist a subgroup of patients who demonstrate a reduction in PSA who would benefit from long-term estramustine phosphate therapy. A drop in PSA may of course merely represent a group with a good prognosis anyway.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Ornstein DK, Rao GS, Smith DS and Andriole GL.	Issue:	1997, 157: 880-3; 883-4

Title:

The impact of systematic prostate biopsy on prostate cancer incidence in men with symptomatic benign prostatic hyperplasia undergoing transurethral resection of the prostate.

Abstract:
Prostate cancer is found in between 10-20% of men undergoing transurethral resection of the prostate of which 95% arise from the transition zone. This retrospective study examines the impact of systematic prostate biopsy on the incidence of prostatic carcinoma in 85 men undergoing TURP for symptomatic prostatic enlargement. All men had elevated PSA and/or suspicious digital rectal examination. Cancer was found in 5 of 29 (17.2% ) of men who had no prior prostatic biopsy and in 9 of 56 (16.1%) of men who had at least 1 prior benign biopsy. The cancer detected was significant (T1B or greater) in nearly 90% of men. Serum PSA and PSA density failed to discriminate between those patients with benign histology and those with malignant. The authors conclude that the move toward medical and minimally invasive techniques for the treatment of BPH may result in a delayed or missed diagnosis of malignancy in up to 15% of men despite pre-operative evaluation with PSA, digital rectal examination and prostate biopsy.

Reviewer: Mark Feneley

Journal:	Cancer Research
Authors:	Joseph IB and Isaacs JT.	Issue:	1997, 57: 1054-1057.

Title:

Potentiation of the antiangiogenic ability of linomide by androgen ablation involves down-regulation of vascular endothelial growth factor in human androgen-responsive prostatic cancers.

Abstract:
This study determined whether angiogenic molecules important in angiogenesis are express in vitro by human prostate cancer cell lines and what effect castration and anti-angiogenic drugs have on them. Castration inhibited the secretion of vascular endothelial growth factor, which normally increases in the presence of hypoxia. Linomide, an anti-angiogenesis drug, was synergistic with castration in reducing VEGF levels, but by itself does not affect levels of VEGF. As both are effective by different routes, their actions are complementary and this bodes well for therapeutic trials.

Reviewer: Mark Feneley

Journal:	Cancer Research
Authors:	Gao AC, Lou W, Dong JT and Isaacs JT.	Issue:	1997, 57: 846-849.

Title:

CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13.

Abstract:
This study showed in rat prostate cancer cell lines that CD44, which is a membrane glycoprotein important in cell-cell and cell-extracellular matrix interactions, is the product of a metastasis suppressor gene. Previous work had demonstrated that KAI1 on human chromosome 11p11.2 could suppress metastasis in some, but not all prostate cancer cell lines. The CD44 gene is close to the KAI1 gene on human chromosome 11p13 and transfection-induced expression of this gene could lead to suppression of metastasis in cells which had normal KAI1.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Skjorten FJ, Berner A, Harvei S, Robsahm TE and Tretli S.	Issue:	1997, 79: 1172-1179.

Title:

Prostatic intraepithelial neoplasia in surgical resections: relationship to coexistent adenocarcinoma and atypical adenomatous hyperplasia of the prostate.

Abstract:
This study looked at the presence of prostatic intraepithelial neoplasia (PIN) in 1,135 consecutive surgical resections. High grade PIN was found more commonly in samples from patients with small tumours. The inter-observer agreement (chance-corrected proportional-agreement) was 0.66 for PIN and 0.89 for carcinoma; the latter may seem low. No association was found between atypical adenomatous hyperplasia and prostate cancer, but data from the follow-up of patients was not included in the analysis.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Wong WS, Chinn DO, Chinn M, Chinn J and Tom WL.	Issue:	1997, 79: 963-974.

Title:

Cryosurgery as a treatment for prostate carcinoma.

Abstract:

Reviewer: Mark Feneley