Androgen Synthesis Inhibitors vs Androgen Receptor Inhibitors and Survival in Metastatic Hormone-Sensitive Prostate Cancer
In brief
Androgen receptor inhibitors linked to 11 more months of survival than abiraterone
In a retrospective study of 3,404 patients with metastatic hormone-sensitive prostate cancer, those treated with apalutamide or enzalutamide had median overall survival of 67.9 months, compared with 57.2 months for those treated with abiraterone. The association persisted in sensitivity analyses, but only a randomized trial can establish whether the treatment choice itself accounts for the difference.
- Journal
- JAMA network open (Q1)
- Published
- 1 October 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Georges Gebrael, Yeonjung Jo, Varun Nandakumar, Zeynep Irem Ozay, Chiara Mercinelli, Gabriel Hooper, et al.
- PMID
- 42900475
- DOI
- 10.1001/jamanetworkopen.2026.39458
Why clinicians should know about it
- Picked for Urology (paper of the day, 23 October 2026): Comparative survival with prostate cancer systemic intensification
Abstract
IMPORTANCE: In metastatic hormone-sensitive prostate cancer (mHSPC), randomized clinical trials directly comparing androgen deprivation therapy intensification using androgen synthesis inhibitors (ASIs) vs next-generation androgen receptor inhibitors (ARIs) are lacking. OBJECTIVE: To compare the outcomes associated with ASI vs ARI intensification therapy among patients with mHSPC in community or academic clinical practices. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of patients diagnosed with mHSPC between February 4, 2013, and April 29, 2024, with follow-up through the July 2024 data cut, providing a median (IQR) follow-up of 25.6 (24.5-26.6) months. Patient-level data were extracted from the nationwide US-based Flatiron Health electronic health record-derived deidentified research database of community and academic practices. Patients with evidence of an mHSPC diagnosis initiating treatment with an ASI (abiraterone acetate) or ARI (apalutamide or enzalutamide) within 3 months prior to or 6 months after an mHSPC diagnosis were eligible. Patients with prior docetaxel receipt were excluded. EXPOSURE: Treatment with an ASI vs an ARI. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS), defined as time in months from mHSPC diagnosis to death or censoring at last recorded activity. RESULTS: Of 3404 patients (median [IQR] age, 73 [66-80] years), 1830 received treatment with an ASI (abiraterone), and 1574 with an ARI (507 apalutamide, 1067 enzalutamide). Following inverse probability of treatment weighting, patients receiving an ARI had significantly longer OS (median, 67.9 months [95% CI, 67.5 months to not reached]) compared with patients treated with the ASI (median, 57.2 months [95% CI, 52.7-63.3 months]) (hazard ratio [HR], 0.74 [95% CI, 0.64-0.87]); P < .001). Results were similar in sensitivity analyses using therapy initiation as the index date (HR, 0.73 [95% CI, 0.62-0.84]; P < .001) and when restricted to index dates on or after December 16, 2019 (HR, 0.67 [95% CI, 0.56-0.81]; P < .001). The association was not modified by insurance status or socioeconomic status. CONCLUSIONS AND RELEVANCE: In this cohort study of 3404 patients with mHSPC, treatment intensification with an ARI was associated with significantly longer OS compared with an ASI. These findings may help guide clinical treatment selection and patient counseling. However, given conflicting clinical practice data across differing database populations, only a randomized clinical trial can definitively answer this question.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.