Watchful Waiting versus Radical Prostatectomy in Early Prostate Cancer

In 2008, study results demonstrated that compared with watchful waiting, radical prostatectomy decreased the risk of metastases, the rate of death from prostate cancer, and the rate of death from any cause. Although the participants in the Scandinavian Prostate Cancer Group Study Number 4 trial were predominantly men whose prostate cancers were detected on the basis of symptoms, rather than by elevated prostate-specific antigen levels, the researchers have noted that prostate cancer events have occurred during the extended follow-up period in men with low-risk disease. To determine whether there is a survival benefit for men with low-risk disease, whether the previously observed lack of benefit in men >65 years of age exists, and whether the absence of increased benefit after 9 years of follow-up persists, the researchers have reported estimates of 15-year results, with a median follow-up period of 12.8 years. The estimates were reported in the New England Journal of Medicine [2011;364(18):1708-1717]. The original study was conducted between October 1989 and December 1999 at 14 centers in Sweden, Finland, and Iceland. The study randomly assigned 695 men with newly diagnosed localized prostate cancer to radical prostatectomy or watchful waiting. Inclusion criteria included <75 years of age, life expectancy of >10 years, no other known cancers, and localized tumor of stage T0d as assessed according to the 1978 criteria of the International Union against Cancer. Follow-up was complete through December 2009, with histopathologic review of biopsy and radical prostatectomy specimens and blinded evaluation of causes of death. A Cox proportional hazards model was used to estimate relative risk with 95% confidence intervals (CIs). There were 347 men in the radical prostatectomy group and 348 in the watchful-waiting group. The 2 groups were similar at baseline; mean age was 65 years. By December 31, 2009, 292 men in the radical prostatectomy group had undergone the procedure and 302 men in the watchful-waiting group had not undergone curative treatment. Median follow-up was 12.8 years (range, 3 weeks-20.2 years). By the end of 2009, 166 of the men in the radical prostatectomy group had died, compared with 201 in the watchful-waiting group. In the radical prostatectomy group, the cumulative incidence of death at 15 years was 46.1% compared with 52.7% in the watchful-waiting group (a difference of 6.6 percentage points, 95% CI, –1.3 to 14.5), corresponding to a relative risk of death in the radical prostatectomy group of 0.75 (95% CI, 0.61-0.92; P=.007) and a number needed to treat of 15 overall (7 in men <65 years of age). Death was due to prostate cancer in 55 men in the radical prostatectomy group and 81 men in the watchful-waiting group. The cumulative incidence of death at 15 years was 14.6 in the radical prostatectomy group and 20.7 in the watchful-waiting group (a difference of 6.1 percentage points; 95% CI, 0.2-12.0), corresponding to a relative risk of death in the radical prostatectomy group of 0.62 (95% CI, 0.44- 0.87; P=.001). The interaction term between age at randomization (<65 years vs ≥65 years) and treatment was significant with respect to overall mortality (P=.003) and remained so when age was considered as a continuous variable (P=.001). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men <65 years of age. Extracapsular tumor growth was found in 132 of the 284 radical prostatectomy specimens. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6-18.4). Gleason score was also highly predictive of the risk of death from prostate cancer; among the 129 men who had tumors with Gleason scores of 2 to 6, only 5 died from prostate cancer. The researchers concluded that, “radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment.”