Long-Term Follow-up in PIVOT Trial Shows No Significant Benefit of Surgery vs Observation for Overall or Prostate Cancer Mortality


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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.1 The long-term follow-up was reported in The New England Journal of Medicine by Timothy J. Wilt, MD, MPH, of the Minneapolis VA Health Care System, 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.2

Study Details

In the trial, 731 men were randomized between November 1994 and January 2002 to 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). Death considered definitely due to prostate cancer or treatment occurred in 4.9% of men assigned to surgery and 6.0% of men assigned to observation. Median overall survival was 13.0 vs 12.4 years. 


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.
— Timothy J. Wilt, MD, MPH

Surgery may have been associated with lower all-cause mortality vs observation among 249 patients with intermediate-risk disease (HR = 0.68, 95% confidence interval [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. The effect of surgery on prostate cancer mortality did not vary by tumor risk category (P = .89 for interaction). Absolute differences were not significant and were 1.4% (95% CI = –3.9 to 6.7) in low-risk disease, 7.3% (95% CI = –0.9 to 15.7) in intermediate-risk disease, and 5.8% (95% CI = –5.9 to 7.2) in high-risk 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); progression was asymptomatic in 24.4% vs 43.9%. Rates were 34.1% vs 61.9% for local progression (16.8% vs 32.4 asymptomatic), 9.1% vs 14.2% for regional progression (6.0% vs 8.2% asymptomatic), and 10.2% vs 14.7% for systemic progression (6.9% vs 10.4% asymptomatic). 

PIVOT TRIAL

  • Long-term follow-up revealed that surgery for localized prostate cancer was not associated with a significant improvement in all-cause or prostate cancer mortality.
  • Surgery was associated with lower frequency of progression and treatment for progression, largely reflecting local or asymptomatic biochemical progression. 

Treatment for disease progression was administered 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 progression (12.4% vs 25.3%). Treatment for systemic progression was given 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). Absolute differences exceeded 30 percentage points. Physician-recorded 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.” ■

DISCLOSURE: The study was funded by the Department of Veterans Affairs, Agency for Healthcare Quality and Research, and National Cancer Institute. For full disclosures of the study authors, visit www.nejm.org.

REFERENCES

1. Wilt TJ, Jones KM, Barry MJ, et al: Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med 377:132-142, 2017.

2. Wilt TJ, Brawer MK, Jones KM, et al: Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 367: 203-213, 2012.


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