Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT).

BACKGROUND: Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain.

OBJECTIVE: To determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer.

DESIGN, SETTING, AND PARTICIPANTS: This study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery.

INTERVENTION: Radical prostatectomy versus observation.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods.

RESULTS AND LIMITATIONS: During 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6-20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70-1.00]; p= 0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: -0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84-1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9-14.3) versus 12.6 yr (95% CI: 11.8-13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality.

CONCLUSIONS: Surgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease.

PATIENT SUMMARY: In this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.