PIVOT is the largest and longest randomized trial conducted in men with early-stage prostate cancer detected during the era of widespread PSA testing. The trial enrolled 731 men and followed them for up to 15 years after randomization. PIVOT results demonstrate that compared to observation, radical prostatectomy did not result in a significant reduction in all-cause or prostate cancer mortality through at least 12 years among men with localized prostate cancer; absolute differences in mortality rates were less than 3%. Results changed little after 8 years and additional follow-up is therefore unlikely to change these findings. Radical prostatectomy caused related harms within 30 days of surgery in 21% of men and urinary incontinence and erectile dysfunction through at least 2 years.
Other Key Findings
PIVOT showed that prostate cancer mortality was infrequent among all men treated with observation (approximately 8%) and rare (3%) in men with PSA values ≤ 10 ng/mL or low-risk disease—important and reassuring findings for men, their families, and physicians.
Noncancer death rates and surgical quality in PIVOT were similar to other studies enrolling men with early-stage prostate cancer. The mean age of 67 years, health status, and comorbidities for men in the trial were similar to most men diagnosed with prostate cancer and to patient populations in other trials. The effect of radical prostatectomy did not vary by patient age, race, health status, or presence of other medical conditions.
As noted, death from prostate cancer was rare in men with low PSA (≤ 10 ng/mL) or low-risk disease treated with observation, and surgery provided no reduction in overall or prostate cancer mortality or risk of bone metastases in such patients. Subgroup analyses indicate that surgery may reduce mortality and bone metastases in men with higher PSA or higher-risk disease. However, subgroup findings should be viewed with caution. Any positive results were based on multiple subgroup assessments, rarely met traditional levels of statistical significance, and often were sensitive to methods of analysis; thus, the findings may be due to chance.
Implications of PIVOT
Three-quarters of men with early-stage prostate cancer have low PSA or low-risk disease. Men diagnosed today and managed with observation likely have even a better prognosis than men enrolled in PIVOT because of increased detection of smaller, more indolent disease. Compared to active surveillance, informing men of the favorable long-term effects of observation on mortality, bone metastases, urinary and erectile function, and quality of life and increasing the use of observation may avert the harms of unnecessary biopsies and interventions while maintaining excellent long-term disease-specific survival.
PIVOT results, combined with other data from randomized treatment and screening trials, indicate that observation should be the preferred treatment strategy for the majority of men currently diagnosed with early-stage prostate cancer. Such a strategy can help men live a similar length of life, avoid death from prostate cancer, and prevent treatment-related harms and costs.
In conclusion, PIVOT demonstrated that surgery did not reduce overall or prostate cancer mortality compared to observation through at least 12 years. While surgery may reduce mortality in the minority of men with PSA greater than 10 ng/mL or high-risk disease, it did not improve outcomes in men with PSA of ≤ 10 ng/mL or low-risk disease. Observation should be recommended as the preferred treatment option. Randomized controlled trials are needed to evaluate new, more effective, and safer screening and treatment approaches for men with aggressive prostate cancer. ■
Timothy Wilt, MD, MPH
Professor of Medicine and Core Investigator
Minneapolis VA Center for Chronic Disease Outcomes Research
and the University of Minnesota School of Medicine, Minneapolis
Chair, VA/NCI/AHRQ CSP#407: Prostate Cancer Intervention Versus Observation Trial (PIVOT)
Disclosure: Dr. Wilt reported no potential conflicts of interest.
