Safety and Treatment Discontinuation of Novel Hormonal Therapies in Metastatic Hormone-Sensitive Prostate Cancer: An Exploratory Real-World Study.

Background/

Objectives

Treatment intensification with novel hormonal therapies is now standard in metastatic hormone-sensitive prostate cancer (mHSPC), but real-world patients are often more heterogeneous than those included in pivotal trials. This study aimed to describe clinical characteristics, safety, treatment discontinuation, disease progression, polypharmacy, and clinically documented drug-drug interactions in a real-world mHSPC cohort.

Methods

We conducted a retrospective observational study including 109 patients with mHSPC who initiated abiraterone, enzalutamide, apalutamide, or docetaxel-based triplet regimens between January 2015 and November 2025. Outcomes included adverse events, discontinuation, PSA50 response at 3 months, time to progression and overall survival. Descriptive analyses and Kaplan-Meier estimates were performed.

Results

Apalutamide was the most frequent first-line treatment (56.9%), followed by abiraterone (23.9%), enzalutamide (11.9%), darolutamide-based triplet therapy (3.7%), and abiraterone-based triplet therapy (3.7%). Median age was 73 years, and median baseline PSA was 16.1 ng/mL. De novo metastatic disease was present in 69.7% of patients, ISUP grade 4-5 disease in 58.7%, high-risk disease according to LATITUDE criteria in 45.9%, and high-volume disease according to CHAARTED criteria in 38.5%. The median Charlson Comorbidity Index was 4, and polypharmacy was observed in 68.8%. Adverse events occurred in 56.0%, and non-death treatment discontinuation occurred in 22.0%. No documented drug-drug interactions requiring treatment modification were recorded. PSA50 response was achieved by 97.2%. Thirteen patients (11.9%) progressed and 18 (16.5%) died. Median time to progression was not reached, and median overall survival was 53.2 months.

Conclusions

Novel hormonal therapies were used in a clinically heterogeneous real-world mHSPC cohort. The findings support individualized treatment assessment and should be interpreted as descriptive and exploratory.