Darolutamide plus ADT showed the highest probability of being the most effective treatment for delaying deterioration in health-related quality of life among ARPI doublets in mHSPC, with a meaningful difference versus apalutamide plus ADT and ADT alone.
Key Findings
Results
Darolutamide plus ADT demonstrated a statistically meaningful delay in time to deterioration in FACT-P total score compared with ADT alone.
Hazard ratio of 0.76 (95% credible interval [CrI] 0.61–0.94) for darolutamide plus ADT versus ADT alone
A Bayesian proportional hazards network meta-analysis (NMA) was used within the Bayesian generalised linear model framework
The outcome measured was time to deterioration in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score
Data were drawn from the ARANOTE, ARCHES, TITAN, and LATITUDE randomised controlled trials
Results
Darolutamide plus ADT showed a meaningful difference in delaying HRQoL deterioration compared with apalutamide plus ADT.
Hazard ratio of 0.74 (95% CrI 0.56–0.99) for darolutamide plus ADT versus apalutamide plus ADT
The credible interval excludes 1.00, indicating evidence of a difference between these two treatments
This comparison was derived indirectly through the NMA as no head-to-head RCTs exist between these agents
Results
Darolutamide plus ADT showed numerically favorable but not statistically meaningful effects on HRQoL compared with abiraterone plus ADT.
Hazard ratio of 0.89 (95% CrI 0.69–1.16) for darolutamide plus ADT versus abiraterone plus ADT
The 95% credible interval crosses 1.00, indicating no evidence of a statistically meaningful difference
The authors described the effect as 'numerically favourable'
Results
Darolutamide plus ADT showed numerically favorable but not statistically meaningful effects on HRQoL compared with enzalutamide plus ADT.
Hazard ratio of 0.79 (95% CrI 0.60–1.04) for darolutamide plus ADT versus enzalutamide plus ADT
The 95% credible interval crosses 1.00, indicating no evidence of a statistically meaningful difference
The authors described the effect as 'numerically favourable'
Results
Darolutamide plus ADT had the highest probability of being the most effective treatment for delaying deterioration in HRQoL across all ARPI doublets evaluated.
This ranking was derived from the Bayesian NMA framework, which inherently produces probability rankings for competing treatments
Comparators included apalutamide plus ADT, abiraterone plus ADT, and enzalutamide plus ADT, all combined with ADT
No specific probability value was reported in the abstract; the finding was described as 'highest probability' across all treatments evaluated
Background
No head-to-head randomised controlled trials directly comparing ARPIs in mHSPC existed, necessitating an indirect NMA approach.
The study included data from four RCTs: ARANOTE, ARCHES, TITAN, and LATITUDE
A Bayesian proportional hazards NMA was selected as the methodological approach to enable indirect comparisons
The absence of direct comparative RCTs is identified as the rationale for the NMA methodology
Conclusions
The study concluded that darolutamide plus ADT may maintain HRQoL longer than other ARPIs and supports its use as a patient-centred treatment option.
The authors state findings 'suggest that darolutamide plus ADT may maintain HRQoL longer than other ARPIs'
Darolutamide plus ADT is described as supporting 'a patient-centred treatment option' in mHSPC
The context is the broader transformation of mHSPC management by ARPIs combined with ADT
What This Means
This research used a statistical technique called network meta-analysis to indirectly compare how four different hormone-based drug combinations affect quality of life in men with metastatic hormone-sensitive prostate cancer (mHSPC) — a form of prostate cancer that has spread but still responds to hormone therapy. Because no studies have directly compared these treatments head-to-head, researchers pooled data from four large clinical trials (ARANOTE, ARCHES, TITAN, and LATITUDE) to estimate how each treatment compares to the others in terms of how long patients maintain their quality of life, measured using a validated patient-reported questionnaire called the FACT-P.
The analysis found that darolutamide combined with standard hormone therapy (ADT) performed the best overall, showing a statistically meaningful advantage in delaying quality-of-life decline compared to ADT alone and compared to apalutamide plus ADT. Darolutamide also appeared numerically better than abiraterone plus ADT and enzalutamide plus ADT, though those differences were not statistically conclusive. Across all treatments studied, darolutamide plus ADT had the highest probability of being the best option for preserving patient quality of life.
This research suggests that when choosing among available androgen receptor pathway inhibitors for mHSPC, the impact on patients' daily wellbeing and quality of life may differ meaningfully between drugs. The findings indicate darolutamide plus ADT may offer an advantage in maintaining quality of life compared to at least some other options in this drug class, which could be an important consideration for patients and clinicians when making treatment decisions alongside other factors like efficacy and side effect profiles.
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N. Shore, Noman Paracha, Howard Thom, Philip Orishaba, Elaine Gallagher, A. Morgans. (2026). Health-related Quality of Life With ARPIs in mHSPC: Insights From a Network Meta-analysis.. European Urology Focus. https://doi.org/10.1016/j.euf.2026.03.001