Kelly Gaudian ^1* Min Jung Koh ² Min Ji Koh ² Ryan Collins ^3* Shaine Eden ^4* Zoya Zwart ^5* Malika Danner ^3* Alan Zwart ^5* Mark Fallick ^6* Deepak Kumar ⁷ Paul Leger ⁵ Nancy A Dawson ^5* Simeng Suy ^3* Sean P Collins ^3*

• ¹ School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
• ² School of Medicine, Georgetown University, Washington, D.C., District of Columbia, United States
• ³ Morsani College of Medicine, USF Health, Tampa, Florida, United States
• ⁴ Biomedical Graduate Education, Georgetown University, Washington, D.C., District of Columbia, United States
• ⁵ Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, United States
• ⁶ Novartis (United States), East Hanover, New Jersey, United States
• ⁷ The Julius L. Chambers Biomedical and Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, United States

Injectable GnRH receptor agonists can improve cancer control when combined with radiotherapy (RT). Relugolix is an oral GnRH receptor antagonist that achieves rapid testosterone suppression. Non-adherence to oral medications due to poor social support or side effects may increase risk of cancer recurrence. This prospective study sought to evaluate early testosterone suppression and relugolix adherence when combined with prostate stereotactic body radiation therapy (SBRT). Utilization of patient-reported outcomes (PROs) to assess adherence and guide intervention may improve oral medication use. This study utilizes the Simplified Medication Adherence Questionnaire (SMAQ) to assess adherence. Relugolix was initiated ≥2 months before questionnaire administration. Total testosterone levels were obtained at the time of SMAQ administration. Castration was defined as serum testosterone ≤ 50 ng/dL. Poor drug adherence was delineated as failure to reach castration or SMAQ non-adherence (any non-adherence answer, missed > 2 doses in last week or since last visit). To compare demographic and clinical characteristics of nonadherent versus adherent patients, t-test, Wilcoxon rank sum test, Chi-square test, and Fisher's exact test were used. A p-value < 0.05 determined statistical significance. Between August 2021 and December 2023, 78 men were treated at Georgetown with relugolix and prostate SBRT per an institutional protocol. The median age was 72, and 41% of patients were non-white. Patients initiated relugolix at a median of 4 months before the SMAQ (2-19 months). 96% of patients achieved castration (≤ 50 ng/dL) at the time of the SMAQ. 96% of men reported always taking relugolix at the appropriate time. 1% discontinued medication due to bothersome side effects, 17% reported forgetting to take the medication, and 4% reported missing a dose during the weekend. 98% and 93% did not miss a dose more than 2 times in the last week and since the last visit, respectively. Overall patient-reported drug adherence was 75%. No patient demographic or clinical characteristic predicted non-adherence. Relugolix allows for high rates of castration and drug adherence when combined with prostate SBRT. Monitoring drug adherence during treatment allows for prompt detection of nonadherence and timely intervention. Future studies should focus on optimally incorporating this questionnaire into patient management.