Surgery vs Observation in Localized Prostate Cancer: Long-Term Follow-up of PIVOT Trial


Key Points

  • Surgery was not associated with a significant improvement in all-cause or prostate cancer mortality.
  • Surgery was associated with a lower frequency of disease progression and treatment for disease progression, largely reflecting local or asymptomatic biochemical disease progression.

After 19.5 years of follow-up in the PIVOT trial, radical prostatectomy was not associated with significantly improved all-cause or prostate cancer mortality vs observation among men with localized prostate cancer. The long-term follow-up data were reported in The New England Journal of Medicine by Wilt and colleagues. An earlier report from the trial showed that surgery was not associated with improved all-cause or prostate cancer mortality after 12 years.

Study Details

In the trial, 731 men were randomized between November 1994 and January 2002 to undergo surgery (n = 364) or observation (n = 367). The current update includes follow-up through August 2014 (minimum of 12 years, maximum of 19.5 years) for all-cause mortality and prostate cancer mortality. Data on disease progression and treatments received are from follow-up through January 2010.

Mortality Outcomes

During 19.5 years of follow-up (median = 12.7 years), death occurred in 61.3% of the surgery group vs 66.8% of the observation group (hazard ratio [HR] = 0.84, P = .06). Death due to prostate cancer or its treatment occurred in 7.4% vs 11.4% (HR = 0.63, P = .06). Median overall survival was 13.0 vs 12.4 years. Surgery was associated with lower all-cause mortality vs observation among 249 patients with intermediate-risk disease (HR = 0.68, 95% CI = 0.50–0.92) but not among 296 with low-risk disease (HR = 0.98, 95% CI = 0.72–1.33) or 157 with high-risk disease (HR = 0.78, 95% CI = 0.54–1.13), with P = .08 for interaction. Surgery was also associated with nonsignificant improvements in prostate cancer mortality among low-risk (HR = 0.74, 95% CI = 0.26–2.13), intermediate-risk (HR = 0.53, 95% CI = 0.25–1.11), and high-risk patients (HR = 0.64, 95% CI = 0.29–1.41), with P = .89 for interaction.

Disease Progression and Treatment

Any disease progression occurred in 40.9% vs 68.4% of patients (HR = 0.39, 95% CI = 0.32–0.48); disease progression was asymptomatic in 24.4% vs 43.9%. Rates were 34.1% vs 61.9% for local disease progression (16.8% vs 32.4 asymptomatic), 9.1% vs 14.2% for regional disease progression (6.0% vs 8.2% asymptomatic), and 10.2% vs 14.7% for systemic disease progression (6.9% vs 10.4% asymptomatic).

Any treatment for disease progression occurred in 33.5% vs 59.7%, in most cases due to increasing or persistently elevated prostate-specific antigen levels (20.3% vs 37.9%) and local disease progression (12.4% vs 25.3%). Treatment for systemic disease progression occurred in 4.7% vs 8.7%. Definitive treatment was given to 20.4% of patients in the observation group, with such treatment being infrequent after 5 years, and to 85.5% of the surgery group, with almost all such treatment occurring within the first year. Androgen-deprivation therapy was given to 21.7% of the surgery group vs 44.4% of the observation group.

Adverse Effects

Higher proportions of patients in the surgery group had urinary incontinence (P < .001 at 1, 2, 5, and 10 years), erectile dysfunction (P < .01 at 1, 2, 5, and 10 years), and sexual dysfunction (P < .05 at 1, 2, and 5 years). Treatment for erectile dysfunction occurred in 14.6% vs 5.4% of patients, and treatment for incontinence occurred in 17.3% vs 4.4%. Disease-related or treatment-related limitations in activities of daily living were greater in the surgery group through 2 years.

The investigators concluded: “After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer 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.”

The study was funded by the Department of Veterans Affairs, the Agency for Healthcare Quality and Research, and the National Cancer Institute.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.