Association of Postoperative Antidepressant and Anxiolytic Exposure With Overall Survival Following Radical Cystectomy for Bladder Cancer.

BACKGROUND: Psychological distress is an important component of cancer survivorship, particularly among patients undergoing radical cystectomy (RC) for bladder cancer. However, the prognostic significance of postoperative psychiatric medication exposure following RC remains unclear. AIMS: To investigate the association between postoperative antidepressant and/or anxiolytic exposure and survival outcomes following RC for bladder cancer. METHODS: This retrospective propensity score-matched cohort study used data from the TriNetX US Collaborative Network. Adult patients who underwent RC for bladder cancer (2005-2025) were identified. Postoperative psychiatric medication exposure was defined as new use of antidepressants (Anatomical Therapeutic Chemical: N06A) and/or anxiolytics (ATC: N05B). The primary analysis evaluated combined antidepressant/anxiolytic exposure, with separate antidepressant-only and anxiolytic-only subgroup analyses. Overall survival (OS) and all-cause mortality were evaluated after 1:1 propensity score matching (PSM). RESULTS: The primary analysis identified 2461 exposed and 7257 unexposed patients, yielding 1521 matched pairs after PSM. Patients exposed to postoperative psychiatric medication were associated with significantly poorer OS than their matched controls (hazard ratio [HR]: 1.377, 95% confidence interval [CI]: 1.261-1.502; log-rank p < 0.001). Similar associations were observed in subgroup analyses. Antidepressant-only exposure was associated with poorer OS (HR: 1.260, 95% CI: 1.161-1.367; p < 0.001), and the anxiolytic-only subgroup demonstrated the strongest association with poorer survival (HR: 1.457, 95% CI: 1.324-1.604; p < 0.001). CONCLUSIONS: Psychiatric medication use may represent a clinically observable marker of psychological burden and survivorship vulnerability following RC. Early recognition of postoperative psychological vulnerability may facilitate timely psycho-oncological support and multidisciplinary survivorship care following RC.