This is an important update from the PIVOT trial, now with nearly 20 years of follow-up. As noted, the authors report no significant improvement in all-cause (HR, 0.84; 95% CI, 0.70–1.01; P = .06) or prostate cancer–specific (HR, 0.63; 95% CI, 0.39–1.02; P = .06) mortality with surgery as compared with observation. There are, however, some notable caveats to consider along with these findings.

First, the study enrolled only 731 of a target accrual of 2000 men and was therefore quite underpowered. Acknowledging the magnitude and direction of the associations measured (hazard ratios and P-values cited above), the failure to meet statistical significance is likely a direct result of the study’s lack of power (type II error). Second, approximately 20% of the men assigned to surgery did not undergo surgery, and 20% of those assigned to observation in fact underwent definitive intervention. With an intention-to-treat analysis, this contamination of treatment arms would certainly be expected to skew the observed effect toward the null. Perhaps additional information could have been weaned from a modified analysis. It is also notable that 74% of the cohort had low-risk cancer, a population which is largely recommended for active surveillance in the contemporary practice setting.

Ultimately, for several reasons, randomized controlled trials are very difficult to conduct in patients with localized prostate cancer. The authors acknowledge this and many of the shortcomings of these data in this important publication. Nonetheless, any commentary on PIVOT should mention its limitations so that readers may consider these findings in the appropriate context.

Follow-up of Prostatectomy versus Observation for Early Prostate Cancer

Timothy J. Wilt, M.D., M.P.H., Karen M. Jones, M.S., Michael J. Barry, M.D., Gerald L. Andriole, M.D., Daniel Culkin, M.D., Thomas Wheeler, M.D., William J. Aronson, M.D., and Michael K. Brawer, M.D.

N Engl J Med 2017; 377:132-142July 13, 2017DOI: 10.1056/NEJMoa1615869