High comorbidity as a predictor of poorer survival and ARPI efficacy in metastatic prostate cancer

Abstract

The prognostic impact of comorbidity burden in metastatic prostate cancer (mPC) remains uncertain. This study aimed to evaluate the association between Charlson Comorbidity Index (CCI) and progression free survival (PFS) and to explore androgen receptor pathway inhibitor (ARPI) outcomes in patients with high comorbidity. Methods: This retrospective multicenter study evaluated the impact of clinical and laboratory characteristics on progression free survival using Kaplan Meier and Cox regression analyses. CCI was dichotomized as <3 vs ≥3 based on the cohort median. In the subgroup of patients with CCI≥3 receiving androgen deprivation therapy (ADT) plus ARPIs, PFS was compared between enzalutamide and abiraterone. Results: A total of 344 patients were included. The median age was 68.6 years (range, 43.7–88.7), and the median follow up was 29.4 months (range, 2.2–145.8). ECOG performance status was 0 in 51.5%, 1 in 43.6% and ≥2 in 4.9% of patients. The median CCI was 3; 141 patients (41.0%) had CCI<3, and 203 (59.0%) had CCI≥3. Median PFS was 40.5 months (95% CI, 25.9–55.1) for CCI<3 and 29.0 months (95% CI, 22.5–35.4) for CCI≥3. Variables significant in univariate analysis were entered into multivariable Cox regression, where CCI≥3 (p=0.046), elevated LDH (p<0.001), and elevated ALP (p=0.033) remained independent adverse prognostic factors for PFS (Table 1). Among patients with CCI≥3 receiving ADT+ARPI, median PFS was 54.3 months with enzalutamide and 34.0 months with abiraterone (log-rank p=0.043). Conclusions: Higher comorbidity burden (CCI≥3) is an independent predictor of shorter PFS in metastatic prostate cancer. Among patients with high CCI receiving ARPI plus ADT, abiraterone was associated with inferior PFS compared with enzalutamide. Comorbidity assessment may guide individualized treatment selection and risk stratification in clinical practice. Univariate and multivariate Cox regression analyses for progression-free survival. Variable Univariate HR (95% CI) Univariate p-value Multivariate HR (95% CI) Multivariate p-value Age (<70 vs. ≥70) 0.86 (0.62–1.19) 0.364 ECOG performance status (≥1 vs. 0) 1.32 (1.06–1.64) 0.015 1.16 (0.78–1.73) 0.470 Charlson Comorbidity Index (≥3 vs. <3) 1.09 (1.01–1.18) 0.034 1.60 (1.07–2.41) 0.022 Elevated ALP 1.72 (1.18–2.51) 0.005 1.00 (1.00–1.00) 0.711 Elevated LDH 1.90 (1.30–2.78) <0.001 1.95 (1.31–2.91) 0.001 Gleason score (≥8 vs. <8) 1.25 (0.86–1.83) 0.244 High-volume disease 2.12 (1.53–2.96 <0.001 1.98 (1.30–3.00) 0.001 De novo metastasis 1.18 (0.80–1.74) 0.395 Bone metastasis 2.08 (1.30–3.33) 0.002 1.28 (0.64–2.54) 0.483 Liver metastasis 1.90 (0.89–4.07) 0.098