Impact of hospitalizations on health-related quality of life and overall survival in metastatic castration-sensitive prostate cancer: Insights from the ARANOTE trial.

53 Background: The impact of hospitalizations on health-related quality of life (HRQoL) and overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) has not been well characterized. Using data from the ARANOTE trial, we evaluated whether hospitalizations which occurred within 60 days prior to outcome data collection – either before or during participation in the trial - have an impact on HRQoL and OS. Methods: HRQoL was assessed using the Functional Assessment of Cancer Therapy–Prostate (FACT-P) instrument. FACT-P total scores from all available study visits were modeled longitudinally with generalized estimating equations. Covariates included number of prior all-cause hospitalizations, hospitalizations due to treatment-related adverse events, baseline pain (<4 vs ≥4), baseline ECOG performance status (0–1 vs 2), fatigue (any grade adverse event during participation in the trial), baseline age, and baseline weight. OS was evaluated using time-varying Cox proportional hazards regression. Covariates for the OS model included treatment, treatment-emergent adverse events, and number of prior all-cause hospitalizations. Results: Both the number of previous hospitalizations (–4.26 points; 95% CI: –6.89 to –1.63; p<0.001) and hospitalization due to treatment-emergent adverse events (–6.14 points; 95% CI: –9.92 to –2.36; p<0.001) were significantly associated with lower FACT-P total scores. Baseline pain ≥4 was the strongest negative predictor of HRQoL (–16.09 points; 95% CI: –19.46 to –12.73; p<0.001). ECOG performance status of 2 at baseline (–6.19; 95% CI: –13.62 to 1.25; p=0.10) and fatigue (–2.32; 95% CI: –7.68 to 3.05; p=0.40) were associated with lower HRQoL but did not reach statistical significance. Age (0.09; 95% CI: –0.08 to 0.25; p=0.29) and baseline weight (0; 95% CI: –0.08 to 0.09; p=0.96) had minimal effects. In survival analyses, the number of prior hospitalizations was strongly associated with mortality with each additional hospitalization increasing the hazard of death by 52% (HR 1.52; 95% CI: 1.39–1.66; p<0.0001). Conclusions: Prior hospitalizations were a consistent determinant of both reduced HRQoL and shorter OS in men with mCSPC, while baseline pain was the strongest driver of HRQoL decline. A post hoc analysis from the ARANOTE trial (Shore et al. 2025), found that darolutamide was associated with lower rates of hospitalization compared to placebo. Taken together, these findings highlight that treatments that decrease hospitalization with favorable tolerability profiles, such as darolutamide, may help sustain quality of life and survival by minimizing hospitalization burden. Clinical trial information: NCT04736199 .