Clinical Question: What is the best treatment for moderately differentiated or well-differentiated prostate cancer?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (single-blinded)

Allocation: Concealed

Synopsis: This study was a three-year follow-up to one originally reported in 2002. Men with localized, well-differentiated, or moderately differentiated prostate cancer were randomized according to World Health Organization grading to radical prostatectomy or watchful waiting. Gleason scores were 2 to 4 for 13 percent of the men, 5 or 6 for 48 percent, 7 for 23 percent, and 8 to 10 for 5 percent. The Gleason score was unknown for 11 percent of patients. Only 5 percent of cancers were detected by screening, although more than 85 percent of the men had a prostate-specific antigen (PSA) level greater than 4 ng per mL (118 pmol per L). Allocation was concealed, outcomes were assessed blindly, and analysis was by intention to treat. The majority of patients, however, stayed in the group to which they were assigned. The median duration of follow-up was 8.2 years, and 10-year follow-up data were available for 222 patients. The researchers prespecified several subgroup analyses by age, Gleason score, and PSA level.

Overall, results were more favorable for radical prostatectomy with an increased duration of follow-up. All-cause mortality was lower in the radical prostatectomy group (27 versus 32 percent; P = .04; number needed to treat [NNT] = 20), as was disease-specific mortality (9.6 versus 14.9 percent; P = .01; NNT = 19). The likelihood of local progression and distant metastases also was lower in the treated group. Radical prostatectomy was especially beneficial in men younger than 65 years; little difference existed between watchful waiting and surgery in patients older than 65 years. Although there was no association between the benefit of surgery and the Gleason score, more than 70 percent of patients had a Gleason score of 5 to 7. Therefore, there were too few patients with lower or higher Gleason scores to confidently assess the benefit of surgery in those groups or in men with screening-detected prostate cancer.

Bottom Line: Radical prostatectomy is better than watchful waiting for men with moderately differentiated or well-differentiated prostate cancer, especially (and perhaps only) in men younger than 65 years. Although these are the best data on treatment in this group to date, cancer was detected by screening in only 5 percent of the men in this study. Whether these data generalize to men with screening-detected prostate cancer is unclear but likely will be assumed by most physicians and their patients. (Level of Evidence: 1b)