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Prostate cancer: prevention, prognosis and progress
Some things have been accomplished, but much remains to be done.
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In considering the topics to discuss in this editorial pertaining to genitourinary cancer a number of advances and conundrums presented themselves as items of interest.
First was the striking and continued progress in developing active drugs in advanced renal cell cancer: sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), temsirolimus (Torisel, Wyeth) are FDA approved and two years ago there was virtually nothing for the vast majority of patients with this disease. As a clinical investigator who spent years doing negative phase-2 trials on RCC, these are heady times! Defining the optimal use of these and other agents in development — as single agents and in combination — will be challenging, but real progress has been made!
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On the other hand, the lack of progress in advanced transitional cell carcinoma (TCC) is disheartening: methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) is equivalent to gemcitabine/cisplatin and there has been nothing new since 2000. This is a disease in which much opportunity exists. The evidence that immunologic approaches may play a role in transitional cell carcinoma is persuasive (viz BCG in superficial disease), and signaling pathways important in transitional cell carcinoma should yield advances through carefully done studies with new agents targeting immune, pro-survival and microenvironment (antivascular agents), but nothing much new so far.
In addition, careful and detailed analysis of the large Prostate Cancer Prevention Trial (PCPT), which compared finasteride vs. placebo in a double blind fashion, clearly provides positive results: Finasteride prevented prostate cancer. About 30% fewer cancers were diagnosed in men taking finasteride compared to men taking placebo. Very careful investigation of the possibility that the cancers that occur in men taking finasteride were more aggressive/higher grade does not support this concern. Like all good clinical trials — and in fact any well–designed experiment — the results of PCPT pose many additional questions:
A) Can we “build” on finasteride?
B) Is there a better 5-alpha-reductose inhibitor?
C) What populations of men might benefit most and least?
D) What are factors that influence and limit adoption of finasteride among men like those entered onto PCPT: age older than 50, PSA ≤ 3.0 ng/mL, “normal” prostate DRE.
Finally, the death of Dr. James Gleason — the “inventor” of the Gleason scoring system — in fall 2008 was the passing of a pioneer. Dr. Gleason invented the most robust and reliable prognostic indicator for prognosis of localized prostate cancer. It is with regret that Dr. Gleason’s death is noted, and it is sobering to recognize that there is nothing substantially better than the Gleason score and clinical stage with which to estimate prognosis. Emphasizing the importance of the quest for better prognostic markers is the realization that deciding who to treat with localized prostate cancer is one of the most important challenges in genitourinary oncology. We should be doing better.
In summary, we have made real progress, progress that I believe will save lives and improve the quality and quantity of survival for many individuals, but we’ve only scratched the surface. We need to do more!
Donald L. Trump, MD, is President and CEO of Roswell Park Cancer Institute and a member of the HemOnc Today Editorial board.