BJU international · 2026
Testosterone breakthrough and outcomes during intensified therapy in metastatic hormone-sensitive prostate cancer: the ARASENS and LATITUDE trials.
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Xiao Xiyue, Ni Xudong, Zhao Yufan, Li Xiaomeng, Wang Shanshan, Wang Hongkai, Ye Dingwei, Wu Junlong, Zhu Yao
Аннотация
OBJECTIVES: To assess whether treatment-period serum testosterone breakthrough >35 ng/dL is associated with clinical outcomes during intensified therapy for metastatic hormone-sensitive prostate cancer.
PATIENTS AND METHODS: We performed post hoc analyses of the experimental arms of the ARASENS (darolutamide plus androgen deprivation therapy [ADT] and docetaxel; ClinicalTrials.gov identifier NCT02799602) and LATITUDE (abiraterone acetate plus prednisone and ADT; NCT01715285) phase III trials. Cohort-specific fixed-window landmark analyses classified exposure as any eligible testosterone result >35 ng/dL after treatment initiation and through Day 147 in the LATITUDE trial or Day 266 in the ARASENS trial. Treatment-initiation/Day-1 and end-of-treatment measurements were excluded. Follow-up began at the landmark. The primary outcome was overall survival (OS); the LATITUDE progression-free survival (PFS) and the ARASENS time to castration-resistant prostate cancer (CRPC) were progression endpoints. Multivariable Cox regression was primary; landmark and time-dependent sensitivity analyses were also performed.
RESULTS: At the landmark, 564 LATITUDE and 578 ARASENS patients were classifiable for OS. In the LATITUDE trial, breakthrough was associated with worse OS (adjusted hazard ratio [HR], 1.49, 95% confidence interval [CI] 1.07-2.08; P = 0.019); the PFS estimate was directionally similar but imprecise (HR 1.40, 95% CI 0.98-2.00; P = 0.065). In the ARASENS trial, the overall associations were not statistically significant for OS (HR 1.18, 95% CI 0.85-1.62; P = 0.322) or CRPC (HR 0.86, 95% CI, 0.60-1.23; P = 0.397). Exploratory piecewise modelling suggested time variation for CRPC (interaction P = 0.028).
CONCLUSION: Testosterone breakthrough >35 ng/dL was associated with worse post-landmark OS in the LATITUDE trial, whereas the overall associations with OS and CRPC in the ARASENS trial were not statistically significant. These within-cohort findings are exploratory and do not establish causality, a difference between treatment mechanisms, or a clinical testosterone target.
PATIENTS AND METHODS: We performed post hoc analyses of the experimental arms of the ARASENS (darolutamide plus androgen deprivation therapy [ADT] and docetaxel; ClinicalTrials.gov identifier NCT02799602) and LATITUDE (abiraterone acetate plus prednisone and ADT; NCT01715285) phase III trials. Cohort-specific fixed-window landmark analyses classified exposure as any eligible testosterone result >35 ng/dL after treatment initiation and through Day 147 in the LATITUDE trial or Day 266 in the ARASENS trial. Treatment-initiation/Day-1 and end-of-treatment measurements were excluded. Follow-up began at the landmark. The primary outcome was overall survival (OS); the LATITUDE progression-free survival (PFS) and the ARASENS time to castration-resistant prostate cancer (CRPC) were progression endpoints. Multivariable Cox regression was primary; landmark and time-dependent sensitivity analyses were also performed.
RESULTS: At the landmark, 564 LATITUDE and 578 ARASENS patients were classifiable for OS. In the LATITUDE trial, breakthrough was associated with worse OS (adjusted hazard ratio [HR], 1.49, 95% confidence interval [CI] 1.07-2.08; P = 0.019); the PFS estimate was directionally similar but imprecise (HR 1.40, 95% CI 0.98-2.00; P = 0.065). In the ARASENS trial, the overall associations were not statistically significant for OS (HR 1.18, 95% CI 0.85-1.62; P = 0.322) or CRPC (HR 0.86, 95% CI, 0.60-1.23; P = 0.397). Exploratory piecewise modelling suggested time variation for CRPC (interaction P = 0.028).
CONCLUSION: Testosterone breakthrough >35 ng/dL was associated with worse post-landmark OS in the LATITUDE trial, whereas the overall associations with OS and CRPC in the ARASENS trial were not statistically significant. These within-cohort findings are exploratory and do not establish causality, a difference between treatment mechanisms, or a clinical testosterone target.