Study: To prolong survival in early-stage prostate cancer that is low-risk, observe instead of operating.
In localized prostate cancer, radical prostatectomy early in the course of the disease did not significantly reduce deaths from all causes or specifically from prostate cancer compared with observation through nearly 20 years, according to longterm follow-up results from the phase 3 Prostate Cancer Intervention Versus Observation Trial (PIVOT). The findings, most notable for men diagnosed with low-risk disease, were presented at the 2017 American Urological Association Annual Meeting held in May in Boston.
“We previously demonstrated no significant difference between surgery versus observation in all-cause or prostate cancer mortality (in this population) through 12 years; however, treatment decisions often require information about very long-term mortality,” said Timothy J. Wilt, M.D., M.P.H., professor of medicine at the University of Minnesota School of Medicine and core investigator at the Minneapolis VA Center for Chronic Disease Outcomes Research, in his presentation at the conference.
The PIVOT study, a randomized, controlled trial for patients with clinically localized prostate cancer, began recruitment in 1994. The followup analysis sought to determine whether radical prostatectomy reduced mortality compared with observation. This is a crucial question for patients, because prostatectomy can cause side effects including incontinence and erectile dysfunction.
The study measured death from any cause, with death from prostate cancer as the secondary endpoint. In the 12-year follow-up, according to Wilt, investigators also addressed bone metastases; disease progression; patient-reported outcomes; and erectile, urinary and bowel dysfunction. The study recruited men who were 75 years or younger, diagnosed within the previous 12 months and were expected to live at least 10 years. Patients could have any grade of prostate cancer, including early-stage disease, as long as they were viable candidates for radical prostatectomy. The levels of prostate-specific antigen (PSA) in their blood, which doctors can use to help determine whether prostate cancer may be present or growing, had to be less than 50 ng/mL.
Based on these criteria, 731 patients were randomized to receive either a radical prostatectomy (n = 364) or observation (n = 367). Observation in the PIVOT study included palliative therapy for symptomatic progression, Wilt said, which is different from commonly used PSA-based monitoring and biopsy-based active surveillance programs with delayed radical intervention. The patients in the observation group were offered palliative therapy or chemotherapy for symptomatic or metastatic disease progression. In this group, while PSA was checked regularly, investigators discouraged its use in treatment decisions unless it reached 20 ng/mL. They also advised against repeated prostate biopsies or eventual treatment with prostatectomy, in order to avoid associated potential harms. However, participating doctors were allowed to monitor and treat patients as they saw fit.
The average participant in the observation arm was 66.8 years old and had a mean PSA of 10.2 ng/mL. The average man in the surgery arm was 67 years old and had a mean PSA of 10.1 ng/mL.