ANDROGEN receptor inhibitors (ARIs) were associated with longer overall survival than androgen synthesis inhibitors (ASIs) among patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a retrospective cohort study of 3,404 patients.
The findings showed a median overall survival of 67.9 months for patients receiving ARIs compared with 57.2 months for those treated with ASIs following inverse probability of treatment weighting. The results suggest a potential survival advantage with ARI-based treatment intensification, although randomised clinical trials are needed to establish comparative effectiveness.
Researchers analysed patient-level data from community and academic clinical practices in the US. Patients diagnosed with mHSPC between February 2013 and April 2024 were included if treatment with an ASI or ARI was initiated within the specified period around diagnosis.
The cohort had a median age of 73 years, with 1,830 patients receiving abiraterone as an ASI and 1,574 receiving an ARI. Among ARI recipients, 507 received apalutamide and 1,067 received enzalutamide. Patients who had previously received docetaxel were excluded.
After adjustment using inverse probability of treatment weighting, ARI treatment was associated with significantly longer overall survival than ASI treatment (median: 67.9 months; 95% confidence interval [CI]: 67.5 months to not reached versus 57.2 months; 95% CI: 52.7–63.3 months; hazard ratio [HR]: 0.74; 95% CI: 0.64–0.87; p<0.001).
Sensitivity analyses produced similar findings when treatment initiation was used as the index date (HR: 0.73; 95% CI: 0.62–0.84; p<0.001) and when analysis was restricted to index dates from December 16, 2019 onwards (HR: 0.67; 95% CI: 0.56–0.81; p<0.001).
The association between treatment strategy and survival was not modified by insurance status or socioeconomic status.
The findings suggest that treatment intensification with ARIs may be associated with improved survival compared with ASIs in routine community and academic clinical practice.
However, the study authors noted that clinical practice data from different database populations have produced conflicting findings. The retrospective design also means that the observed association cannot establish that ARI treatment caused the longer survival.
Randomised clinical trials remain necessary to definitively compare these treatment strategies. Until such evidence is available, the findings may help inform treatment selection and discussions with patients with mHSPC.
Reference
Gebrael G et al. Androgen synthesis inhibitors vs androgen receptor inhibitors and survival in metastatic hormone-sensitive prostate cancer. JAMA Netw Open. 2026; 9;(10):e2639458.
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