Multimodal analgesia strategies enhance postoperative recovery and mitigate inflammatory responses in women undergoing elective surgery for endometrial cancer: a retrospective cohort study

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries, with rising global incidence attributed to population aging, obesity, and metabolic syndrome. Surgical resection is the cornerstone of treatment, but perioperative pain management remains challenging. Traditional opioid-centric regimens are effective for acute pain but are associated with adverse effects that can hinder recovery and potentially compromise oncologic outcomes. Multimodal analgesia, integrating non-opioid agents and regional techniques, is increasingly advocated but lacks disease-specific, large-scale comparative evidence in gynecologic oncology. Methods: A retrospective cohort study was conducted at a tertiary teaching hospital in Southwest China, including 650 women undergoing elective surgery for histologically confirmed endometrial cancer between January 2020 and January 2025. Patients were stratified into four groups according to perioperative analgesic regimens: (1) opioid-dominant IV PCA, (2) opioid-sparing plus NSAIDs, (3) epidural/regional adjunct, and (4) fully multimodal analgesia (regional, NSAIDs/acetaminophen, reduced opioids). Co-primary outcomes were prolonged hospitalization (>7 days) and any postoperative complication (Clavien-Dindo grade II or higher). Secondary endpoints included pain scores, incidence of postoperative nausea and vomiting (PONV), time to first ambulation/flatus, and perioperative immune-inflammatory markers (NLR, CRP). Multivariable logistic regression and linear mixed-effects models were used to adjust for potential confounders. Results: Baseline demographic and clinical characteristics were well balanced across groups. Patients receiving multimodal or regional-based regimens had significantly lower opioid consumption and mean pain scores on postoperative day 1 (NRS: 3.2 vs. 4.8, P<0.001) and lower PONV incidence (17.0% vs. 30.9%, P = 0.003) compared to opioid-dominant PCA. Multimodal and regional strategies were associated with earlier ambulation/flatus and shortened hospital stay (mean 6.5 vs. 8.2 days, P<0.001). The incidence of postoperative complications was lowest in the multimodal group (13.0% vs. 21.8%, P = 0.04). Postoperatively, NLR and CRP elevations were significantly attenuated in multimodal and regional groups (both P<0.001). Adjusted analyses confirmed that multimodal analgesia independently reduced the risk of prolonged hospitalization (OR 0.52, 95% CI 0.31-0.87, P = 0.013) and complications (OR 0.55, 95% CI 0.30-0.99, P = 0.048). Subgroup analyses demonstrated consistent benefit across age, BMI, surgical approach, tumor stage, and comorbidity strata. Conclusion: Comprehensive multimodal analgesia significantly reduces opioid consumption, improves pain control, accelerates postoperative recovery, and attenuates perioperative inflammatory responses in women undergoing surgery for endometrial cancer. These findings support the integration of multimodal analgesia into standard perioperative care protocols in gynecologic oncology, with the potential to enhance both clinical and biological outcomes. Prospective multicenter studies are warranted to validate these results and explore long-term oncologic implications.