Authors Wilt TJ, Jones KM, Barry, MJ, et al.
Review Date October 2017
Citation N Engl J Med 2017; 377: 132-142
The authors previously found no significant difference in mortality between men who underwent surgery for localised prostate cancer and those who were treated with observation only over 12 years of follow-up of the PIVOT trial. However, there is still uncertainty regarding non-fatal health outcomes and longer term mortality.
To determine all-cause and prostate-cancer specific mortality over almost 20 years of follow-up; and to describe disease progression, treatments received, and patient-reported outcomes during the original follow-up period of 12 years.
From November 1994 through January 2002, 731 men with localized prostate cancer were randomly assigned to radical prostatectomy or observation (PIVOT trial). From the original follow-up period to January 2010, follow-up was extended to August 2014 for the primary outcome of all-cause mortality and the main secondary outcome of prostate-cancer mortality (minimum 12 years, maximum 19.5 years follow-up).
Disease progression (local, regional, systemic or biochemical (PSA) progression, symptomatic or asymptomatic), treatments received (surgery, radiation, hormone therapy, chemotherapy, immunotherapy), and patient-reported outcomes (urinary incontinence, erectile/sexual dysfunction, worry about health, “bother” due to the cancer or the treatment, physical discomfort, satisfaction with sexual function, functional limitations due to cancer or treatment) were assessed until January 2010.
During 19.5 years of follow-up (median, 12.7 years), 223 of 364 men (61.3%) assigned to surgery died from any cause compared to 245 of 367 men (66.8%) assigned to observation (absolute difference in risk = 5.5 percentage points; 95% confidence interval [CI], -1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, -0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06).
Surgery was associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, -10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, -11.5 to 16.1) (P=0.08 for interaction).
Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression.
Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation over 10 years of follow-up. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through two years follow-up.
After nearly 20 years of follow-up among men with localised prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer specific mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression.
Points to Note
- After nearly 20 years follow-up the absolute difference in all-cause mortality between men assigned to surgery and those assigned to observation was less than 6 percentage points and for prostate-cancer specific mortality the difference was 4 percentages points.
- The between-group differences in mortality were slightly larger than at the 12-year follow-up point but they were still not statistically significant, although sub-group analysis suggests that those with intermediate-risk prostate cancer may derive a mortality benefit from surgery.
- The between-group differences in urinary incontinence and erectile/sexual dysfunction were large and favoured observation over surgery.
- Long-term bother, physical discomfort, worry about health and limitations in activities were similar between groups.
- Although more men in the observation group had progression of their disease, treatment was mostly for local, asymptomatic progression, especially elevated PSA level.
- The results presented here combined with other trials show that long-term prostate cancer is low among men with localised prostate cancer under observation with the benefit of avoiding the harms of active treatment.
- It should be noted that this American study was initiated early in the era PSA testing and the relative benefits of biopsy-based active surveillance (recently a more common treatment option in Australia) were not assessed.