What should we do for men who have a rising prostate-specific antigen (PSA) level after radical prostatectomy? A study by Schroder and associates  in European Urology addressed this question with a prospective, randomized, placebo-controlled trial aimed at preventing PSA progression. The study was done using dutasteride, which was compared with placebo. Men were randomly assigned to receive either of the 2 treatments for 2 years. The primary outcomes were time to PSA doubling as well as other parameters of progression. The results were very encouraging in that they found a very significant reduction in progression rates for men who were given dutasteride.
The treatment was well controlled, but there were limitations in this study. First, nearly a third of the almost 300 men discontinued the study prematurely, and nearly twice as many patients discontinued it in the placebo group compared with the treatment group, so it may have created a significant bias. Another problem was that the men and the doctors knew the PSA levels as the treatment was proceeding, so there could have been a bias in selecting the men who stayed on the trial and those who did not. Lastly, we have to ask ourselves how important PSA progression is in terms of accurately predicting long-term survival, and there we have more uncertainty.
In the United States, the Food and Drug Administration does not recognize PSA parameters for giving approval for treatments. This leaves us with a question: What should we do with these data in terms of counseling men who have biochemical progression after undergoing a radical prostatectomy? Is it reasonable to offer them dutasteride at the present time even though it is not approved? It is certainly available. Or is it possible that, by affecting PSA in some way, we are preventing patients from being offered other therapies that may indeed affect survival? These are questions that we cannot answer at this time, but I would urge caution in saying to men that, at this time, dutasteride is an appropriate thing to use if your PSA is rising.
We need more information, and without other measures of disease progression besides PSA, it is possible that we are making the wrong conclusion. For now, it would be nice to have additional data, and I expect that this study will continue to report on further follow-up. The bottom line at this time is that I don't think there is enough information yet to recommend dutasteride to men with a rising PSA level, but it certainly can be discussed. I look forward to your comments.
1. Schroder F, Bangma C, Angulo JC, et al. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomized, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). Eur Urol. 2012 Nov 23. [Epub ahead of print] http://www.europeanurology.com/article/S0302-2838(12)01337-1/abstract Accessed December 19, 2012.