Real-world determinants of testosterone recovery following androgen deprivation therapy in patients with localized prostate cancer.

Abstract

353 Background: Androgen deprivation therapy (ADT) is a cornerstone of localized prostate cancer management, yet testosterone recovery after cessation varies. Understanding clinical and treatment-related predictors of recovery may inform patient counseling and optimize therapeutic planning. This study aims to identify factors associated with likelihood of, and time to, testosterone recovery following ADT at a large safety-net institution. Methods: A retrospective chart review was completed on all patients treated with ADT and radiation for localized or regionally advanced prostate cancer at an urban, safety-net hospital between 2013 and 2024. We conducted multivariable regression analyses to evaluate predictors of testosterone recovery using logistic regression, and time to recovery using Cox proportional hazards models. Covariates included duration of ADT (short vs long course), use of GnRH agonist vs antagonist, combined androgen blockade, baseline testosterone level, age at diagnosis, and comorbidities (hypertension [HTN], diabetes mellitus [T2DM], cardiovascular disease [CVD], hyperlipidemia [HLD]). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results: A total of 191 patients were included in this study. Median age at diagnosis was 67.3 years. During the study period, 71.2% of patients had testosterone recovery. Those without recovery were monitored for median 30.0 months. Short-course ADT was significantly associated with faster recovery (HR=1.54, 95% CI 1.06-2.24, p=0.023) and greater odds of testosterone normalization (OR=3.48, 95% CI 1.38-8.76, p=0.008). Use of a GnRH antagonist was also associated with accelerated recovery (HR=2.86, 95% CI 1.52-5.38, p=0.001). Cardiovascular disease was linked to a modestly faster recovery (HR=1.50, 95% CI 1.00-2.25, p=0.048), while the impacts of HTN (HR=0.75, 95% CI 0.44-1.28, p=0.29), T2DM (HR=0.81, 95% CI 0.57-1.15, p=0.24), and HLD (HR=0.69, 95% CI 0.47-1.00, p=0.051) were not significant. Older age was inversely associated with testosterone recovery (OR=0.93, 95% CI 0.89-0.98, p=0.002), and low baseline testosterone levels were a strong negative predictor (OR=0.16, 95% CI 0.06-0.45, p<0.001). Other variables, including combined androgen blockade and comorbidity burden, were not significantly associated with outcomes. Conclusions: Shorter duration of ADT and GnRH antagonist use were associated with more rapid testosterone recovery, while older age and lower baseline testosterone level significantly reduced the likelihood of testosterone normalization. These findings suggest that both treatment selection and patient baseline characteristics play critical roles in recovery trajectories following ADT. Further prospective validation is warranted to guide personalized treatment duration and recovery expectations.