The Society of Urologic Oncology annual meeting expressed the overall theme of exploring strategies to delay tumor progression in prostate cancer. Principle topics were the current state of chemoprevention, optimal timing of early hormonal therapy and novel research in advanced prostate cancer.

An overview of the current chemoprevention trials was given. Notably, the SELECT trial, which is testing the value of selenium and vitamin E in prostate cancer prevention, has met its accrual goal with 32,453 enrolled 27 months in advance of planned closure. Trial results are anticipated by 2014. The REDUCE trial studying the role of dutasteride [a type I and type II 5 alpha reductase agent] is on its way to enrolling 8000 subjects. The participants will be those men with a serum PSA value of 2.5 -10 ng/ml who undergo a negative 10 core prostate needle biopsy. The REDUCE trial is not just a reiteration of the prostate cancer prevention trial [PCPT] since this agent is a type I and type II inhibitor of 5 alpha reductase and demonstrates profound inhibition of plasma and prostatic dihydrotestosterone levels. The ViP trial testing Vioxx(rofecoxib) at 25 mg per day is currently accruing 15,000 men with a PSA of 2.5 to 10.0 ng/ml who have undergone a negative needle biopsy.

Two additional studies, SWOG 9917 and PRP-1 are evaluating the effect of selenium or selenium in combination with vitamin E and soy products on the disease progression of those men found to have high grade prostatic intraepithelial neoplasia.

An update of the PCPT was given reviewing the known findings of the study as well as clarifying a few issues. The overall finding of a 25% reduction in overall period prevalence of prostate cancer in those subjects taking finasteride has been tempered by the slight increase in higher grade prostate cancer. Essentially there were 354 fewer cases of moderate to lower grade cancer and 54 more cases of higher grade cancer in those taking medication. There was essentially no change in those with score 7 disease with all the increase coming in Gleason 8-10 tumors. Unlike the breast cancer prevention trial, which demonstrated an increased risk over time of developing endometrial cancer in those subject taking tamoxefin, the risk of being diagnosed with high grade prostate cancer was the same over the 7 years of monitoring. The high rate of prostate cancer detection is a profound aspect of this trial since a detection rate of 24% was encountered compared to the pre-study estimate of 6%. It was noted that the majority of higher grade lesions were detected in those patients with lower PSA values. Further analysis of this data will be necessary to get a better handle on the risk of cancer over-detection by current methods.

A European and American perspective of the PCPT was then presented. In Europe, those cases of prostate cancer detected are felt to be more aggressive; therefore, any decrease in the risk is attractive. At this time however, the data available do not warrant the general recommendation to employ finasteride as a chemopreventative therapy. The US spokesman noted that the Gleason grading system has not been validated in men receiving hormonal therapy and that there is a 5 fold risk reduction for each instance of higher grade prostate cancer. Those with a positive family history or at other reason for greater risk may benefit from such therapy. Clearly there is a need to develop markers that can accurately predict the biological significance of the detected tumors. However, a general recommendation for the use of finasteride as a chemopreventative agent can not yet be made.

An update and analysis of the early vs. delayed therapy ECOG trial in stage D1 prostate cancer patients demonstrated that this small study was well balanced in its initial randomization and that the results demonstrating an advantage with early therapy have been maintained with a more mature analysis. This was a group of T3 N+ patients and it is unclear that patients with lower stage disease would benefit from early therapy. Further analysis of the adjuvant bicalutamide trial focused on the NORDIC trial and those patients in the watchful waiting treatment arm. In those patients with T3/4 disease an overall survival advantage of approximately 30% was noted, while those patients with T1/2 disease demonstrated improved survival in the placebo group. This latter finding is not completely understood and it appears that the difference in survival is due to differences in non-cancer deaths in this sub-group. In the watchful waiting group, a benefit from early therapy was noted in those patients with a baseline PSA of 25-32. Also in the area of early therapy, general meta analysis suggest that there is a disease specific survival benefit of approximately 12% from early hormonal therapy which is diluted when one considers deaths from all causes.

The last portion of the program dealt with newer therapies for advanced disease. The current standard for androgen independent prostate cancer [AIPC] is mitoxantrone and corticosteroids which demonstrates a quality of life benefit. Antitubulin based strategies have progressed to the completion of two large phase III studies to be discussed at the American Society of Clinical Oncology [ASCO] meeting next month, SWOG 9916 comparing taxotere and estramustine to mitoxantrone and prednisone, and TAX 327 investigating weekly vs. once every 3 weeks taxotere alone. Both studies are powered to detect a 33% difference in survival.

Clinical work on atrasatan, an endotheolin type A receptor inhibitor was presented. While this can have some effects on cell growth or pain, it is becoming clearer that the main impact of this therapy is in the prevention of osteoblastic bone formation. Present studies demonstrate an improvement in time to clinical progression in those patients with AIPC. Further phase III trials are in progress for this novel therapy that targets bone metabolism. The potential value of calcitriol and taxotere were also reported which described newer formulations of calcitriol allowing for easier administration. Lastly a novel therapeutic strategy of Genasense [BCL-2 antisense RNA] plus taxotere was described in a phase II study that demonstrated a 56% PSA response and data to suggest that these responses were due to the ability to develop a steady state of antisense expression in the tissue.

Written by S.Bruce Malkowicz, MD, a Contributing Editor with UroToday.

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