Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort

Abstract

Purpose In a recent large prospective study, vasectomy was associated with modestly higher risk of prostate cancer, especially high-grade and lethal prostate cancer. However, evidence from prospective studies remains limited. Therefore, we assessed the associations of vasectomy with prostate cancer incidence and mortality in a large cohort in the United States. Patients and Methods We examined the association between vasectomy and prostate cancer mortality among 363,726 men in the Cancer Prevention Study II (CPS-II) cohort, of whom 7,451 died as a result of prostate cancer during follow-up from 1982 to 2012. We also examined the association between vasectomy and prostate cancer incidence among 66,542 men in the CPS-II Nutrition Cohort, a subgroup of the CPS-II cohort, of whom 9,133 were diagnosed with prostate cancer during follow-up from 1992 to 2011. Cox proportional hazards regression modeling was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Results In the CPS-II cohort, vasectomy was not associated with prostate cancer mortality (HR, 1.01; 95% CI, 0.93 to 1.10). In the CPS-II Nutrition Cohort, vasectomy was not associated with either overall prostate cancer incidence (HR, 1.02; 95% CI, 0.96 to 1.08) or high-grade prostate cancer incidence (HR, 0.91; 95% CI, 0.78 to 1.07 for cancers with Gleason score ≥ 8). Conclusion Results from these large prospective cohorts do not support associations of vasectomy with either prostate cancer incidence or prostate cancer mortality.

Fig 1.

Study population flowchart showing exclusions resulting in a cohort of eligible men with vasectomy status determined from their wives’ reports. CPS-II, Cancer Prevention Study II.

Fig A1.

Misclassification of vasectomy status could have occurred because of under-reporting of vasectomy at enrollment and missed vasectomies after enrollment. The figure illustrates the observed rate ratio as a function of the proportion of men classified as unvasectomized who were actually vasectomized. The form of this function is justified in the following equations. The observed rate ratio comparing vasectomized versus unvasectomized men is: (Rate observed in men classified as vasectomized)/(Rate observed in men classified as unvasectomized). If the true rate of prostate cancer mortality is M in unvasectomized men, and 1.20M in vasectomized men (based on the rate ratio of 1.20 observed in the Health Professional Follow-Up Study), x is the proportion of men classified as unvasectomized who were actually vasectomized, and a weighted average is used to calculate the rate in the denominator in terms of M, then the observed rate ratio is: 1.20/[(1 − x)(1M) + x(1.20M)]. This expression simplifies to 1.20/(1 + 0.20x), which is plotted in the figure. Attenuation of the true rate ratio is relatively modest even when 10% of men classified as unvasectomized were actually vasectomized.