Patient adherence and early biochemical outcomes following relugolix with stereotactic body radiation therapy (SBRT) for unfavorable prostate cancer.

526 Background: Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventional radiotherapy. Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Methods: This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Relugolix was initiated at least 2 months prior to SBRT. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone < 20 ng/dL. Poor drug adherence was delineated as failure to reach profound castration. PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and < 0.2 ng/mL during the first 4 months post SBRT. Results: Between July 2021 and January 2023, 52 men were treated at Georgetown with Relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were black and 28.8% were obese (BMI ≥30 kg/m 2 ). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were > Grade Group 3. 44 patients were intermediate- and 8 were high-risk. The disease volume was high (mean 43.6% of total cores involved). Patients initiated Relugolix at a median of 3.6 months prior to SBRT with a median of 6.2 total months. 92.3%of patients achieved profound castration during Relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue Relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Conclusions: Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. Given the potential benefits of Relugolix over injectable GnRH receptor agonists, its usage may be preferred, especially in specific patient populations (fear of needles, prior cardiovascular events). We observed a 96% compliance rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients can consistently and successfully follow an oral ADT protocol in a real-world setting. Future studies should focus on barriers to medication access.