• Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York. jes9171@nyp.org.
• Department of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, New York.
• Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York.
• Department of Public Policy, Harvard Kennedy School, Cambridge, Massachusetts.
• Department of Urology, Massachusetts General Hospital, Boston, Massachusetts.

Background: Vasectomy has been implicated as a risk factor for prostate cancer in multiple epidemiologic studies over the past 25 years. Whether this relationship is causal remains unclear. This study examines the association between vasectomy and prostate cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which randomized men to usual care or annual prostate cancer screening.Methods: We performed a retrospective analysis of 13-year screening and outcomes data from the PLCO trial. Multivariable Cox proportional hazards regression stratified by study arm and age at vasectomy was performed.Results: There was an increased risk of prostate cancer in men who had undergone a vasectomy and were randomized to the usual care arm of the study (adjusted HR, 1.11; 95% confidence interval, 1.03-1.20; P = 0.008). There was no association between vasectomy and diagnosis of prostate cancer in men randomized to the prostate cancer screening arm. Only men undergoing vasectomy at an older age in the usual care arm of the study, but not the prostate cancer screening arm, were at increased risk of being diagnosed with prostate cancer.Conclusions: Vasectomy was not associated with prostate cancer risk among men who were screened for prostate cancer as part of a clinical trial, but was associated with prostate cancer detection in men receiving usual care.Impact: The positive association between vasectomy and prostate cancer is likely related to increased detection of prostate cancer based on patterns of care rather than a biological effect of vasectomy on prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(11); 1653-9. ©2017 AACR.