Long-term follow-up found no significant differences in all-cause or disease-related mortality in men with early prostate cancer randomized to either radical prostatectomy or to observation. Surgery led to more adverse events, but less treatment for disease progression. “In light of the protracted disease course and extended survival of many patients, treatment decisions often require information about additional treatments received, patient-reported outcomes, and very-long-term mortality,” wrote study authors led by Timothy J. Wilt, MD, MPH, of the University of Minnesota School of Medicine in Minneapolis.
A previous report from this study showed no difference in mortality outcomes through 12 years. The new analysis includes follow-up out to 19.5 years for a cohort of 731 men diagnosed with localized prostate cancer and randomized to either radical prostatectomy (364 patients) or observation (367 patients). Results were published online ahead of print today in the New England Journal of Medicine.
The cumulative incidence of death was 61.3% in the surgery patients, and 66.8% in the observation patients, for a hazard ratio (HR) with surgery of 0.84 (95% CI, 0.70–1.01; P = .06). Although the absolute difference in mortality risk was not significant, it did increase from 3.1 percentage points at eight years to 5.5 percentage points at the end of follow-up. The median survival was 13 years with surgery and 12.4 years with observation.
There were a total of 69 deaths attributable to prostate cancer (65 to disease and 4 to treatment). The cumulative incidence was 7.4% with surgery, and 11.4% with observation, for an HR of 0.63 (95% CI, 0.39–1.02; P = .06).
Though the effect of surgery on mortality did not change significantly based on patient characteristics, there were some numerical variations. In those under 65 years of age, the absolute difference in all-cause mortality was –1.5 percentage points at 8 years, and 12 percentage points at the end of follow-up. In older men, the absolute difference at the end of follow-up was only 2.6 percentage points.
In patients with intermediate-risk disease, there was a 14.5 percentage point difference in all-cause mortality in favor of surgery. But in those with low-risk disease, the difference was only 0.7 percentage points, and in high-risk patients it was 2.3 percentage points.
Any disease progression occurred in 40.9% of surgery patients, and in 68.4% of observation patients. Treatment for progression was used in 33.5% of surgery patients and in 59.7% of those assigned to observation. The frequency of treatments for local progression was lower with surgery across all risk categories.
The incidence of incontinence and erectile dysfunction were substantially higher among those assigned to surgery. With regard to men reporting the use of absorbent pads due to incontinence, absolute differences exceeded 30 percentage points across all time points.
“After nearly 20 years, the absolute difference in all-cause mortality between men assigned to surgery and those assigned to observation was less than 6 percentage points, and the absolute difference in prostate-cancer mortality was 4 percentage points,” the authors wrote, and they suggested that the absolute differences are most worthy of focus in this study. They added that these findings are generally consistent with other large trials comparing surgery and observation.