Combination Therapy Expands for Veterans With Metastatic Prostate Cancer
A large Veterans Health Administration study offers new insight into how treatment strategies for metastatic hormone-sensitive prostate cancer (mHSPC) have evolved and how different therapeutic approaches affect survival. The analysis of more than 6000 US veterans shows that use of combination regimens has increased significantly in recent years and is associated with improved outcomes compared with androgen deprivation therapy (ADT) alone.
The retrospective cross-sectional study included 6216 veterans with de novo mHSPC diagnosed between 2013 and 2022. All patients received ADT within 3 months of diagnosis, and subsequent treatments were tracked within 4 months of ADT initiation. Investigators noted a steady rise in the adoption of intensified treatment. In 2020, 54.0% of eligible veterans received combination therapy, compared with 63.1% by 2022. Younger patients and those with fewer comorbidities were more likely to receive intensified treatment.
Among the 4106 veterans treated between 2017 and 2022, combination therapy was linked to a clear survival advantage. Median overall survival (OS) reached 40.3 months compared with 33.0 months with ADT monotherapy (hazard ratio [HR], 0.80). Clinical progression-free survival (PFS) also improved, with delays in time to castration resistance or death. The findings reinforce the growing recognition that treatment intensification can meaningfully extend life in this patient population.
A major clinical question concerns whether androgen receptor pathway inhibitors (ARPIs) or docetaxel should be prioritized in combination regimens, particularly for patients with high-volume disease. Among 1174 veterans with high-volume mHSPC, OS did not differ between ARPI and docetaxel regimens (32.3 months vs 34.7 months; HR, 1.06). However, ARPIs conferred a PFS benefit (18.7 months vs 16.0 months; HR, 0.80; P = .001). A multivariable model confirmed no OS difference between the two treatment approaches.
In low-volume disease, the pattern was similar. Among 366 veterans, OS was comparable for ARPI and docetaxel regimens (68.4 months vs 55.3 months; HR, 0.81), while ARPIs again improved PFS (39.7 months vs 24.0 months; HR, 0.57). These findings suggest that while both strategies can achieve similar long-term survival, ARPIs may delay disease progression more effectively across disease volumes.
The study provides important real-world evidence to guide oncologists treating veterans with mHSPC. The results underscore the survival benefit of adding systemic therapy to ADT and clarify that both ARPIs and docetaxel are viable partners, though their clinical profiles differ. ARPIs may be particularly valuable for extending the time to progression, while docetaxel remains an option with similar overall survival outcomes.
“In this cross-sectional study of veterans with de novo mHSPC, use of combination therapies increased over time and were associated with longer survival compared with ADT monotherapy,” the authors concluded. They also noted that “future research into the role of docetaxel is needed to elucidate the benefit of chemotherapy in mHSPC.”
For veterans with mHSPC, the findings reinforce the need to move beyond ADT alone whenever possible, especially in younger and fitter patients. When choosing between ARPI-based and docetaxel-based combinations, clinicians should weigh progression-free benefits of ARPIs against the chemotherapy option’s shorter but intensive course. Both approaches remain acceptable standards of care, but real-world patterns suggest ARPIs are increasingly favored.
Reference
Schoen MW, Doherty J, Eaton D, et al. Treatment patterns and survival among veterans with de novo metastatic hormone-sensitive prostate cancer. JAMA Netw Open. 2025;8;(5):e259433. doi:10.1001/jamanetworkopen.2025.9433
