Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer

Background: Understanding competing risks for mortality is critical in determining prognosis among men with non-metastatic castration-resistant prostate cancer (nmCRPC), a disease state that often affects older men and has substantial heterogeneity in risk of cancer mortality. We sought to determine the impact of age, comorbidity, and PSA doubling time (PSADT) on competing risks for mortality in men with nmCRPC. Methods: We conducted a retrospective analysis of 1238 patients diagnosed with nmCRPC in 2000–2015 in the SEARCH database. Multivariable Cox proportional hazards and competing risks regression were used to determine the hazards of overall, prostate cancer-specific (PCSM), and other-cause mortality (OCM) across age, Charlson comorbidity index (CCI), and PSADT subgroups. Results: Men with nmCRPC were elderly (median age 77) and had substantial comorbidity burdens (CCI > 1 n = 701, 57%). Multivariable Cox analysis showed higher CCI was associated with higher hazard of OCM, while slower PSADT was associated with lower hazard of PCSM across all age subgroups. Among those with CCI ≥ 3 (vs. CCI0), the hazard ratio of OCM was 2.7 (95% CI 1.1–6.3), 2.0 (95% CI 1.1–3.6), and 2.5 (95% CI 1.5–4.0) for those aged <70, 70–79, and ≥80, respectively. Among those with PSADT ≥ 9 months (vs. < 9 months), the hazard ratios for PCSM were 0.5 (95% CI 0.3–0.9), 0.6 (95% CI 0.4–0.9), and 0.6 (95% CI 0.4–0.9) for those aged <70, 70–79, and ≥80. Competing risks curves revealed PCSM was the predominant cause of death for those with PSADT < 9 months across all age and comorbidity groups. PCSM and OCM were relatively equal competitors for mortality among those with PSADT≥9 months except those aged > 80 with CCI ≥ 3, in whom OCM was the predominant cause of death. Conclusions: Among men with nmCRPC, age, comorbidity, and PSADT are associated with risk and cause of death and may assist clinicians in counseling patients regarding cancer prognosis.