Xerostomia following lutetium-177 PSMA radioligand therapy in metastatic prostate cancer: Associations with accelerated fatigue and dental treatment onset in a propensity-matched real-world analysis.

e24086 Background: Radioligand therapy (RLT) with lutetium-177 (177Lu)-labeled prostate-specific membrane antigen (PSMA) ligands is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC), but xerostomia is a frequent adverse effect due to off-target salivary gland uptake, with prevalence rates of 22% to 87%. The long-term implications of xerostomia on patient outcomes, such as electrolyte imbalances, fatigue, neurological disorders, mortality, and need for dental treatments, remain understudied. Methods: This retrospective cohort study used deidentified electronic health records from the TriNetX federated network ([Deprecated 11-20-2024] COVID-19 Research Network, 88 healthcare organizations). Cohorts included patients with prostate cancer (ICD-10-CM C61 or C80.1) who received 177Lu-PSMA-617 or 177Lu-dotatate (HCPCS A9607 or A9513). Cohort 1 (non-xerostomia) excluded xerostomia codes (K11.7, R68.2, T66.XXXA); Cohort 2 included them. Propensity score matching (PSM) balanced cohorts on demographics, diagnoses, and laboratory values. Analysis was conducted on January 24, 2026. Results: Pre-PSM, Cohort 1 had 1875 patients; Cohort 2 had 122. Post-PSM, both had 122 patients (predominantly White [81.1%]). Malaise/fatigue had higher risk in xerostomia group (29.5% vs 44.8%; RR, 0.658; 95% CI, 0.376-1.152; P = .153) and shorter median survival (1280 vs 372 days; log-rank P = .052). No significant differences in fluid/electrolyte imbalance risk (28.9% vs 31.8%; risk ratio [RR], 0.909; 95% CI, 0.558-1.481) or median survival (1182 vs 609 days; log-rank P = .239). Nervous system disorders showed similar risk (22.4% vs 35.7%; RR, 0.629; 95% CI, 0.302-1.309; P = .209) and median survival (not reached vs 728 days; log-rank P = .066). Mortality was identical (36.9% both; RR, 1.000; 95% CI, 0.720-1.389). Dental treatments showed similar risk (15.9% vs 24.5%; RR, 0.650; 95% CI, 0.317-1.334; P = .237) and median survival (1316 vs 479 days; log-rank P = .063). Conclusions: Xerostomia after 177Lu-RT was associated with increased fatigue risk and earlier onset, leading to an increase in the burden of illness on the patient. Other associations were not found but can be due to the small number of patients that were used in this retrospective study. This preliminary finding highlights the need for further research to identify other associations and/or disparities.