A systematic review of randomized trials in localized prostate cancer.

INTRODUCTION Most treatment studies of localized prostate cancer are observational in nature. The recent publication of a large randomized trial of radical prostatectomy (RP) versus watchful waiting (WW) has focused increased attention on the treatment of localized prostate cancer. We reviewed all published randomized trials that compared different primary treatment modalities for localized prostate cancer. MATERIALS AND METHODS We performed a comprehensive Medline search from 1966 to March 2003 to identify all English-language randomized trials of RP, external-beam radiotherapy (EBRT), brachytherapy, watchful waiting, and primary androgen-deprivation therapy in localized prostate cancer. RESULTS Nine publications dealing with four separate randomized trials were identified. Two studies examined RP and WW; one study examined RP and EBRT; one study examined RP and EBRT, with both groups receiving neoadjuvant and adjuvant androgen-deprivation therapy. WW, in both studies, refers to no treatment until palliative therapy is required. Two of the four trials, conducted in Veterans Administration medical centers, had small sample sizes and were plagued by several methodological limitations. Neither trial was able to convincingly demonstrate an advantage of RP over WW or RP over EBRT. One trial of RP versus EBRT included patients with both localized and locally advanced disease. The fourth trial demonstrated statistically significant reduction in disease-specific mortality, local progression, and development of metastases in patients with primarily clinically detected, well- or moderately well differentiated prostate cancer who underwent RP as compared to WW. CONCLUSIONS There is high-quality evidence from one randomized trial in favor of surgery over watchful waiting with palliative intent for non-high grade localized prostate cancer. However, most tumors in this study were clinically diagnosed rather than screen-detected. Further randomized trials examining the treatment of screen-detected, localized prostate cancer are needed; several are currently underway.