The Relationship Between Androgen Deprivation Therapy Duration and External Beam Radiotherapy With or Without a Brachytherapy Boost in High-Risk Prostate Cancer

Abstract

The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown.A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates.Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment.A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.