Salvage Androgen Deprivation Therapy Use After Definitive Radiotherapy With vs Without Androgen Deprivation Therapy in Prostate Cancer

BACKGROUND: For patients with unfavorable intermediate or high risk localized prostate cancer receiving definitive radiotherapy, androgen deprivation therapy reduces recurrence and improves survival but is underutilized due to toxicity concerns. Patients who forgo initial ADT may later require salvage ADT. Robust real world risk estimates can guide counseling. PATIENTS AND METHODS: We conducted a retrospective cohort study using SEER-Medicare. Men aged 66 years diagnosed from 2010 to 2021 and treated with external beam radiotherapy were included. Exposure was concurrent ADT with radiotherapy versus radiotherapy alone. Salvage ADT was defined as initiation after the initial treatment period. We estimated cumulative incidence of salvage ADT accounting for death as a competing risk and used Fine-Gray models to obtain adjusted sub-distribution hazard ratios, controlling for demographics, tumor characteristics, and facility factors. RESULTS: Among 5,092 patients with unfavorable intermediate-risk disease, 61.17% received concurrent ADT with definitive RT. Among 6,970 patients with high-risk disease, 89.60% received concurrent ADT with definitive RT. At 5 years, the adjusted cumulative incidence of salvage ADT was 3.53% (RT with ADT) versus 6.07% (RT alone) for unfavorable intermediate-risk, and 5.92% vs 19.17% for high-risk patients. On multivariable analysis, concurrent ADT with definitive RT was associated with a lower risk of salvage ADT in both the unfavorable intermediate-risk group (SHR, 0.56; 95% CI,A 0.45-0.70; p < 0.01) and the high-risk group (SHR, 0.26; 95% CI, 0.21-0.31; p < 0.01). Higher PSA was also associated with increased risk for salvage ADT for both risk groups, and higher Gleason score was also associated with increased salvage ADT in high-risk patients. CONCLUSIONS: Omission of initial ADT during RT is associated with an increased risk of salvage ADT in unfavorable intermediate-risk and high-risk prostate cancer. These real-world, population-based estimates help inform patient counseling and facilitate personalized treatment decisions.