Association of Cancer Stage and Comorbidity Burden with 12-Month Clinically Significant Cognitive Decline After...

Background and Objectives: We aimed to determine whether gynecologic cancer-related factors are associated with postoperative clinically significant cognitive decline (CCD) after accounting for age and comorbidity using competing-risk models. Materials and Methods: We performed a retrospective cohort study of adult women undergoing index surgery for gynecologic cancer at a tertiary university hospital. CCD was defined as new clinician-documented cognitive impairment, neurology/psychiatry consultation, or initiation of cognition-targeted pharmacotherapy ≥30 days postoperatively. Competing events were all-cause death and major neurologic events/hospice. We fit Fine-Gray subdistribution hazard models adjusted for age, Charlson Comorbidity Index (CCI), cancer stage, and treatment intensity, and evaluated a prespecified age × stage interaction. Results: Among 1023 eligible patients (mean age 62.4 ± 11.8 years; 41.3% International Federation of Gynecology and Obstetrics [FIGO] stage III-IV; median CCI 3 [IQR 2-5]), CCD occurred in 98 (9.6%). The 12-month cumulative incidence of CCD was 11.2% accounting for competing risks. Advanced stage was independently associated with higher CCD risk (sHR 1.85, 95% CI 1.27-2.69; p = 0.001). A significant age × stage interaction was observed (p < 0.001), with the strongest association in patients ≥70 years (sHR 2.48, 95% CI 1.61-3.81). Perioperative factors associated with CCD included open surgery (sHR 1.54) and postoperative delirium (sHR 2.76); these findings should be interpreted as associative signals rather than validated causal treatment targets. A stratified blinded chart review of 160 patients (80 flagged-positive and 80 unflagged controls) supported the CCD definition (PPV 88.8%; sensitivity 72.1%; specificity 94.3%; NPV 91.5%). Visit-frequency adjustment confirmed robustness (advanced stage sHR 1.78; p = 0.003). Conclusions: Gynecologic cancer-related factors, particularly advanced stage, are independently associated with CCD after accounting for competing risks, and high-risk phenotypes (age ≥70, FIGO III-IV) may benefit from perioperative pathways integrating cognitive screening, delirium prevention, and neurocognitive follow-up.