Non-cancer causes of death in patients with hormone-sensitive prostate cancer.

Abstract

55 Background: The overall survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly improved, while a substantial proportion of patient’s deaths are non-cancer-related. Characterizing the causes of non-cancer related deaths may guide preventive and supportive strategies. Methods: We performed a retrospective multicentric study of all patients (pts) diagnosed with mHSPC between 2010 and 2025 who received androgen deprivation therapy (ADT) alone, ADT + docetaxel, ADT + androgen receptor pathway inhibitors (ARPI), or triplet therapy. Clinical and tumor data, comorbidities and mortality information were extracted from electronic medical records. Deaths were classified as PC–related or non-cancer; non-cancer deaths were subclassified (infectious, cardiovascular, respiratory, other cancer, unknown; single-category causes pooled as “Miscellaneous”). Overall survival (OS) was estimated by Kaplan–Meier. Group comparisons used Kruskal–Wallis for continuous variables and Fisher’s exact test for categorical variables. Results: Among 565 pts with mHSPC, 93 received ADT alone, 125 ADT plus docetaxel, 321 ADT plus ARPI, and 26 triplet therapy (ADT + docetaxel + ARPI). During a median follow-up of 44.6 months (4.5 - 228.9), 382 pts (68%) died. Thirty-five deaths (6.2% of pts, 9% of deaths) were attributed to non-cancer causes before progression to castration-resistant prostate cancer (CRPC). Median OS in this subgroup was 16 months (95% CI: 12.6–43.8). Leading causes were infectious (12/35, 34%; 17% Covid-19), cardiovascular (6/35, 17%), other cancer (5/35, 14%), unknown cause (4/35, 11%), and respiratory (3/35, 9%); the remaining single-category causes (neurological, trauma, pulmonary embolism, digestive, euthanasia) totaled 5/35 (14%). No deaths were attributed to febrile neutropenia. Pts who died of cardiovascular causes tend to have a lower median age at death compared to those with infectious disease (72 vs 83.5 years respectively). They also showed higher functional status (median Barthel 100 vs. 60) and a lower comorbidity status (median 2 vs. 3), although non significant. Most pts (71%) were on active systemic therapy at the time of death, most commonly ADT + ARPI (46%). No significant differences were observed between cause of death and treatment received. Conclusions: Non–cancer related deaths occurred in 6% of mHSPC patients, mainly due to infections and cardiovascular events, the latter potentially linked to ADT and ARPIs. These findings highlight the importance of early cardiovascular risk assessment and preventive interventions to improve survival in this population.