Association Between Primary Local Treatment and Non–prostate Cancer Mortality in Men With Nonmetastatic Prostate Cancer

Objective: To assess the association between local treatment modality, surgery or radiotherapy, and non–prostate cancer and cardiovascular mortality in patients treated for nonmetastatic prostate cancer, given the high competing risk of mortality in this population. Methods: We performed a population-based, retrospective cohort study of men treated for nonmetastatic prostate cancer in Ontario, Canada, from 2002 to 2009. Patients treated with surgery and radiotherapy were matched on demographics, comorbidity, and cardiovascular risk factors. The primary outcome was non–prostate cancer mortality. Outcomes were compared using the Fine and Gray subdistribution method with generalized estimating equations. We used a previously published technique to quantify the prevalence and strength of residual confounding necessary to account for observed results. Results: We examined 5393 pairs of matched men. The 10-year cumulative incidence of non–prostate cancer mortality was higher among patients who underwent radiotherapy (12%) than surgery (8%; adjusted subdistribution hazard ratio [HR] 1.57, 95% confidence interval 1.35-1.83). Patients treated with radiotherapy also had an increased risk of cardiovascular mortality (adjusted HR 1.74, 95% confidence interval 1.27-2.37). Hypothetical residual confounders would have to be both strongly associated with non–prostate cancer mortality (HRs > 2.5) and have highly differential prevalence to nullify the observed effect. Conclusion: Among patients carefully matched on cardiovascular risk factors, those treated with radiotherapy had an increased risk of non–prostate cancer mortality and cardiovascular disease. Because of the observational nature of the data, the potential for confounding remains. The magnitude and prevalence of potential residual confounders required to account for differences in treatment effects for prostate cancer was quantified.