Immunomodulation in healing: neoadjuvant immunochemotherapy reduces major wound complications and accelerates recovery in oral cancer surgery.

[BACKGROUND] Major wound complications after oral squamous cell carcinoma surgery remain a significant cause of morbidity, delaying adjuvant therapy and impairing recovery. Neoadjuvant immunochemotherapy may improve pathological responses, but its impact on postoperative wound healing is poorly understood. This study evaluates whether neoadjuvant immunochemotherapy is associated with fewer major wound complications and faster healing compared to neoadjuvant chemotherapy or upfront surgery.

[METHODS] In this retrospective cohort study, 692 patients with locally advanced oral squamous cell carcinoma undergoing curative-intent surgery were divided into three cohorts: neoadjuvant immunochemotherapy (n=235), neoadjuvant chemotherapy (n=300), and upfront surgery (n=157). The primary endpoint was incidence of major wound complications (Clavien-Dindo ≥III) within 90 days. Secondary endpoints included time to complete wound sealing, length of postoperative stay, readmissions, reoperations, and time to adjuvant radiotherapy.

[RESULTS] Major wound complication rates were significantly lower in the neoadjuvant immunochemotherapy cohort (9.2%) compared to neoadjuvant chemotherapy (17.8%) and upfront surgery (21.5%) (p<0.001). Multivariable analysis confirmed neoadjuvant immunochemotherapy was independently associated with reduced complication risk versus upfront surgery (adjusted odds ratio 0.40, p=0.001) and neoadjuvant chemotherapy (adjusted odds ratio 0.48, p=0.007). Time to complete wound sealing was significantly shorter in the neoadjuvant immunochemotherapy cohort (adjusted hazard ratio 1.85 vs. upfront surgery, p<0.001). Neoadjuvant immunochemotherapy patients also had shorter hospital stays, fewer readmissions, and earlier initiation of adjuvant radiotherapy. Within the neoadjuvant immunochemotherapy cohort, poor pathological response, shorter treatment-surgery interval (<28 days), heavy smoking, free flap reconstruction, and high blood loss were independent risk factors for complications.

[CONCLUSIONS] Neoadjuvant immunochemotherapy is associated with a significant reduction in major wound complications and accelerated wound healing in patients with locally advanced oral squamous cell carcinoma surgery, supporting its integration into perioperative care pathways to improve surgical recovery.