2825 - The Impact of Neoadjuvant Relugolix on Multi-Dimensional Patient-Reported Fatigue

M. J. Koh¹, J. Hsueh², S. Shah¹, L. Gallagher¹, M. J. Koh¹, A. Zwart³, P. Leger⁴, N. Dawson⁴, S. Suy³, and S. P. Collins⁵; ¹Department of Radiation Medicine, Georgetown University Hospital, Washington, DC, ²Department of Urology, Georgetown University Hospital, Washington, DC, ³Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, ⁴Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, ⁵MedStar Georgetown University Hospital, Washington, DC

Purpose/Objective(s): Androgen deprivation therapy has been shown to improve cancer control when combined with radiotherapy. Relugolix is an oral GnRH receptor antagonist that achieves rapid profound testosterone suppression, which may increase the perception and/or impact of fatigue. This study sought to evaluate neoadjuvant relugolix-induced fatigue in prostate cancer patients prior to the start of stereotactic body radiation therapy (SBRT). Materials/

Methods: Relugolix was initiated at least two months before SBRT. The 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was collected at baseline and one hour prior to SBRT initiation. A five-point scale from 0 (not at all) to 4 (very much) was used to score individual items. Overall scores range from 0-52 and individual item scores were transformed from 0-100, with higher scores reflecting less fatigue. Five “experience” items asked about self-perceptions on fatigue, and eight “impact” items asked about fatigue affecting daily activities. Items were evaluated for statistical significance (paired t-test, p < 0.05) and clinical significance (minimally important difference (MID); ± 0.5 standard deviation from baseline).
Results: Between March 2021 to December 2023, 89 men were treated at a single academic institution with neoadjuvant relugolix and SBRT. Median age was 72 years (range: 49-87). 34% of patients were black and 25% were obese (BMI =30 kg/m²). Median initiation of relugolix was 4.5 months prior to SBRT. Average overall scores were 45.6 at baseline and 41.0 at SBRT initiation. This difference was statistically and clinically significant (p < 0.01, MID = 3.55). For each individual item, there was a noticeable increase in the number of patients who experienced problems after relugolix. These changes were statistically significant for 11 of 13 items. Three of five experience items showed a clinically significant increase. Notably, only two of eight impact items were clinically significant.
Conclusion: Our study shows that relugolix significantly increases fatigue, affecting multiple areas of life. Interestingly, the fatigue does not appear to generally impact a patients’ ability to carry out normal activities. Nevertheless, patients demonstrate frustration with being too tired to carry out these activities. It is essential for clinicians to counsel prostate cancer patients on the impact of neoadjuvant relugolix on quality-of-life issues like fatigue.

Abstract 2825 – Table 1

	Statistical Significance (p-value)	Clinical Significance (MID)
Overall Score	<0.01	+
Experience Items
Fatigue, Weakness, Tiredness	<0.01	+
Listlessness, Loss of Energy	<0.01	—
Impact Items
Trouble starting things from tiredness, Trouble finishing things from tiredness, Needing sleep	<0.01	—
Inability to do usual activities	0.04	—
Frustrated by being too tired to do activities	<0.01	+
Too tired to eat	0.03	+