Timing and Resolution of Bothersome Hot Flashes Following Short Course Oral Gonadotropin-Releasing Hormone Receptor Antagonist Relugolix, and Stereotactic Body Radiotherapy for Localized Prostate Cancer

Background Androgen deprivation therapy (ADT) has been shown to improve cancer control when combined with radiation therapy. Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, suppresses testosterone, causing several hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly bothersome. This study sought to evaluate the timeline of hot flashes following a short course of relugolix, and stereotactic body radiotherapy (SBRT) for unfavorable localized prostate cancer. Methods IRB approval was obtained for retrospective review of prospectively collected data. Patients were treated at MedStar Georgetown University Hospital per an institutional protocol. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 before relugolix initiation, the first day of SBRT treatment, and at subsequent follow-up visits. All patients were treated with the robotic SBRT (Accuray Inc.). Total testosterone levels were measured before SBRT and at each follow-up. Results From January 2021 to September 2023, 89 localized prostate cancer patients (63 intermediate, 20 high-risk, and 6 recurrent) at a median age of 72 years (range 49-93) were treated with a short course of relugolix (average 6.25 months, range 3-29 months) and prostate SBRT. The median time to cessation of hot flashes was around nine-months post-SBRT when the median testosterone had recovered in 56% (50) of patients, with a median testosterone of 230 ng/dL. The incidence of burdensome hot flashes (a moderate to big problem) returned to baseline nine-months post-SBRT (0%) with a cumulative incidence of 57% (51). The median EPIC-26 hot flash score of 98.7 declined to 49.0 at one-month post-SBRT and returned to baseline by nine-months post-SBRT. These differences were statistically significant (p< 0.01) and clinically significant (MCID=4.45). Testosterone recovery (>230 ng/dL) occurred in 97% (86) of patients 12-months post-SBRT. Conclusions Bothersome hot flashes occur in more than 50% of men treated with short-course relugolix and SBRT. Resolution of hot flashes occurs in the majority of men by nine-months post-SBRT. Hot flash resolution mirrored testosterone recovery at relatively low levels. Reassurance of the temporary nature of hot flashes may reduce patient anxiety and limit associated bother.