QuickScan Reviews in Urology, April 30 2009

Objective: To compare finasteride plus flutamide versus flutamide alone in men with biochemically recurrent prostate cancer. Design/Methods: This was a non-randomized phase II study which enrolled 56 men with biochemically recurrent prostate cancer. Men were sequentially assigned to their treatment arm. The first 36 were treated with combination low-dose flutamide plus finasteride while the subsequent 20 were treated with low-dose flutamide alone. Patients were treated for up to 84 months and responses were assessed based on changes in PSA. Results: Men on combined therapy had a greater decrease in PSA with lower nadir PSA levels after correcting for their baseline PSA values. Men on combined therapy were more likely to have a complete response, ie, an undetectable PSA. There was a trend toward better progression-free survival for the combination treatment group on univariate analysis, but this was not statistically significant. Patients on the combination arm had a higher incidence of toxicity, though overall toxicity was mild and manageable. Conclusions: Low-dose flutamide either alone or in combination with finasteride may be an alternative to traditional androgen deprivation therapies in men with biochemically recurrent prostate cancer, and phase III randomized trials of these regimens should be undertaken. Reviewer's Comments: Every urologist has faced the problem of the man who has undergone therapy for his prostate cancer, but now the serum PSA has begun to rise, suggesting biochemical recurrence. The anxiety and stress this provokes in patients and their families can be profound. Often, the choice boils down to treat with androgen deprivation therapy (ADT) or observe. There is growing appreciation that ADT has significant morbidity that gets progressively worse with time, strongly arguing for alternative approaches in these men who are typically asymptomatic with respect to their cancer. Banez et al present a study that purports to show that a solution may be the use of low-dose flutamide with or without the addition of finasteride. Their report, while demonstrating low toxicity and an ability to lower PSA, unfortunately adds relatively little to our understanding of how to treat these men. This is mainly because it was not powered adequately to be called a phase II trial for either of its individual arms, and it was not randomized, making comparison across the 2 arms of this very small trial virtually impossible. Therefore, it would be inappropriate for the reader to conclude from this study that low-dose flutamide, with or without finasteride, is the appropriate routine next step in the management of men with biochemically recurrent prostate cancer. Rather, as the authors themselves point out, it will take a well designed, randomized trial comparing one or both of these strategies to traditional ADT to answer this question.