3264 - Ultra-Short-Course Hormone Therapy for Intermediate Risk Prostate Cancer Treated with Definitive Radiotherapy: Retrospective Analysis of a National Healthcare System

T. Pflederer^1,2, S. R. Miller^1,2, W. C. Jackson², D. A. Elliott^1,2, M. Green^1,2, R. T. Dess², and A. K. Bryant^1,2; ¹Department of Radiation Oncology, Veterans Affairs Ann Arbor Health System, Ann Arbor, MI, ²Department of Radiation Oncology, University of Michigan, Ann Arbor, MI

Purpose/Objective(s): Short course androgen deprivation therapy (ADT; 4-6 months) can improve oncologic outcomes when combined with definitive radiotherapy for intermediate-risk prostate cancer, particularly in the concurrent/adjuvant setting. While a previous randomized trial compared 0, 3, and 6 months of ADT in the neoadjuvant setting, we lack randomized trials of ultra-short ADT courses (<4 months) in the concurrent/adjuvant setting. As early discontinuation of ADT due to side effects or patient preference is common, we sought to leverage variation in delivered ADT duration to assess the potential oncologic benefit of ultra-short courses. Materials/Methods: We identified all newly diagnosed favorable (FIR) or unfavorable intermediate risk (UIR) prostate cancer cases in the national Veterans Health Administration (VHA) from Jan 2000 to Dec 2019 treated with definitive radiotherapy with or without concurrent/adjuvant ADT with GnRH agonists. Concurrent/adjuvant ADT was defined as the first ADT injection occurring between 30 days prior and 90 days after the first radiation fraction. ADT courses were categorized by duration (none, < 2, 2-3.9, or 4-6 months). A 6-month landmark analysis was performed to account for immortal time bias. The primary outcome was development of metastatic prostate cancer, ascertained from clinical notes using a validated natural language processing algorithm. The secondary outcome was overall survival (OS). Multivariable Cox regressions compared ADT duration groups adjusting for age, self-reported race, Charlson Comorbidity Index, number of prior negative biopsies, grade group, initial PSA, and tumor stage.

Results: We identified 19,233 patients with FIR (64%) or UIR (36%) prostate cancer treated with definitive radiotherapy. Of the patients, 63% were White, 31% were Black, and the median age was 67 years old (IQR 63-72). Among patients who received concurrent/adjuvant ADT with a calculable duration, 533 received < 2 months, 513 received 2-3.9 months, and 604 received 4-6 months. 1,373 metastatic prostate cancer events were observed; 10-year unadjusted cumulative incidence of metastatic prostate cancer was 6.0% overall (95% CI 5.6 – 6.4). In multivariable Cox regression, relative to no ADT, 4-6 months of ADT was associated with an improvement in metastatic prostate cancer (adjusted HR [aHR] 0.54, 95% CI 0.36-0.80, p=0.002) as was 2-3.9 months (aHR 0.68, 95% CI 0.48-0.97, p=0.03). < 2 months of ADT was not associated with benefit (aHR 0.89, 95% CI 0.64-1.25, p=0.5). There was no difference in OS.

Conclusion: For intermediate risk prostate cancer, ultra-short course ADT (2-3.9 months) may reduce metastatic prostate cancer incidence compared to no ADT, though the magnitude of benefit may be less than standard short course (4-6 months). <2 months of ADT had no statistically significant benefit.