Abstract A101: Comorbidities, guideline-concordant treatment, and prostate cancer-specific mortality in California, 2011-2021: A competing risks mediation analysis

Abstract

Prostate cancer (PCa) is the second-leading cause of cancer-related mortality among men in the United States (US). Comorbidity burden is common among men with PCa and is associated with lower survival, potentially through reduced receipt of guideline-concordant treatment. However, the extent to which receipt of guideline-concordant treatment mediates this association, and whether it differs by race and ethnicity remain unclear. We examined the association between comorbidity burden and PCa-specific mortality among men diagnosed in California (2011–2021) and estimated the proportion mediated by guideline-concordant treatment, overall and by race and ethnicity. We conducted a retrospective cohort study of men diagnosed with PCa in California (2011–2021) using California Cancer Registry data. Comorbidity burden was classified using the Charlson Comorbidity Index (CCI) into three groups: no comorbidities (CCI=0), low burden (CCI=1–2), and high burden (CCI≥3). We estimated subdistribution hazard ratios (sHRs) using Fine-Gray models, treating non-PCa death as a competing event, with adjustment for age, race and ethnicity, nativity, marital status, socioeconomic status, insurance, smoking, stage, grade, and receipt of guideline-concordant treatment. Guideline-concordant treatment was defined by stage and risk group at diagnosis, adapted from a SEER-based NCCN-concordance framework. The proportion of this association mediated by guideline-concordant treatment was estimated using four-way effect decomposition, stratified by race and ethnicity. Between 2011 and 2021, 116,974 men were diagnosed with PCa in California and had record of CCI. Among them, 10,022 (8.57%) died of PCa. Of these, 3,441 (34.33%) and 2,282 (22.77%) had a low and high comorbidity burden, respectively. Compared to patients with no comorbidity burden, those with a low and high comorbidity burden had 27% (sHR=1.27; 95% CI: 1.20-1.35) and 83% (sHR=1.83; 95% CI: 1.68-1.99) higher hazard of PCa-specific mortality, respectively. When stratified by race and ethnicity, the adjusted sHRs for high comorbidity burden were 1.84 (95% CI: 1.66–2.04) among non-Hispanic White men, 1.47 (95% CI: 1.17–1.84) among non-Hispanic Black patients, 2.01 (95% CI: 1.33–3.02) among US-born Hispanic patients, 1.65 (95% CI: 1.19–2.29) among non-US-born Hispanic patients, and 2.31 (95% CI: 1.74–3.07) among Asian/Pacific Islander patients. Guideline-concordant treatment explained little of the high-comorbidity-mortality association overall (proportion mediated: 0.4%; 95% CI: 0.0%, 0.8%), a pattern consistent across all racial and ethnic groups (range: −0.3% to 1.5%). Comorbidity burden was strongly associated with PCa-specific mortality across different racial and ethnic groups in California, an association largely unexplained by guideline-concordant treatment. This suggests treatment access alone is unlikely to close the mortality gap, and points to comorbidity-informed management, rather than treatment-access interventions alone, as a priority for men with PCa. Diego Alvarez-Lopez, Joel Sanchez Mendez, William Hernandez, Lihua Liu, Mariana C. Stern. Comorbidities, guideline-concordant treatment, and prostate cancer-specific mortality in California, 2011-2021: A competing risks mediation analysis [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr A101.