Introduction

Given the protracted course of prostate cancer (PC) progression, competing risks of mortality is a key consideration in determining prognosis and treatment in all stages of the disease. We sought to examine the impact of age, Charlson Comorbidity Index (CCI), and PSA doubling time (PSADT) on all-cause mortality (ACM), prostate cancer-specific mortality (PCSM), and other-cause mortality (OCM) in a nationally representative sample of men with non-metastatic castration-resistant PC (M0/Mx CRPC)._x000D_

Methods

We analyzed 1,238 men diagnosed with M0/Mx CRPC in 2000 or later from 8 Veterans Affairs hospitals in the SEARCH database. CCI and PSADT were calculated at the time of M0/MX CRPC diagnosis, and cause of death was defined as PCSM or OCM. Men were divided into subgroups based on age (<70, 70-79, and ≥80), CCI (0, 1, 2, and 3+), and PSADT (<9 months, ≥9 months). Multivariable Cox proportional hazards analysis and competing risks regression analysis were used to determine the relative impact of age, CCI, and PSADT on ACM, PCSM, and OCM. Models were adjusted for race, year of diagnosis, site, biopsy Gleason score, PSA at CRPC, primary treatment, months from androgen deprivation to CRPC, and PSA velocity.

Results

Men in our sample were generally older (<70, n=344; 70-79, n=418; ≥80, n=476), and the majority had CCI ≥2 (n=701). Competing risk regression analysis revealed that the risk of PCSM was appreciable for all subgroups, particularly among those with PSADT<9mos. However, the hazard of OCM was substantially higher for older, sicker men with high PSADT (Figure 1). For example, among men aged ≥80, those with CCI ≥3 and PSADT≥9 mos, cumulative incidence of PCSM/OCM at 5 years was 20%/50% compared with 30%/19% for CCI 0 and PSADT<9mos. Multivariable analysis showed that higher comorbidity burden predicted higher hazard of OCM across all ages; among those with CCI ≥3 (vs. 0), hazard ratios for OCM were 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.

Conclusions

Among men with M0/Mx CRPC, age, comorbidity, and PSADT are predictive of cause of death. Understanding the competing risks of PCSM and OCM is a critical consideration when counseling patients regarding prognosis and treatment of advanced PC.

Funding

None