Peri-diagnostic NSAID use and all-cause mortality in ovarian cancer: nationwide cohort study

Inflammation influences the progression and treatment resistance of epithelial ovarian cancer, and nonsteroidal anti-inflammatory drugs (NSAIDs) have shown anticancer effects in other malignancies; however, their impact on ovarian cancer survival, particularly in Asian populations, remains unclear. Using the Korean Nationwide Cancer Public Library Database, we identified 14,736 women newly diagnosed with ovarian or fallopian tube cancer between 2012 and 2019. NSAID use was classified as Only POST (within 6 months after diagnosis only) or PRE & POST (both before and after diagnosis), and NSAID frequency was categorized as low (< 1 day/week), intermediate (1–3 days/week), or high (≥ 4 days/week). The primary outcome was all-cause mortality, analyzed with Cox proportional hazards models adjusting for demographic, clinical, and treatment-related factors, with subgroup analyses performed by initial treatment sequence (surgery-first vs. chemotherapy-first). During a median follow-up of 2.91 years, 4,108 deaths (27.9%) occurred. In the fully adjusted model, NSAID timing (PRE & POST: HR 0.94, 95% CI 0.88–1.01) and post-diagnosis frequency (high: HR 0.92, 95% CI 0.82–1.04) were not significantly associated with mortality in the overall cohort. However, in surgery-first subgroup, PRE & POST (HR 0.89, 95% CI 0.82–0.97) and high-frequency use (HR 0.84, 95% CI 0.73–0.98) were associated with significantly lower mortality compared with their counterparts. No associations were found in chemotherapy-first subgroup. Peri-diagnostic NSAID use was not significantly associated with all-cause mortality in the overall cohort. PRE & POST and high-frequency use were associated with lower mortality among patients initially treated with surgery; however, these associations require cautious interpretation given multiple potential residual confounding.