Efficacy and safety of neoadjuvant chemoimmunotherapy for locally advanced oral squamous cell carcinoma: a two-center real-world retrospective cohort study

Neoadjuvant chemoimmunotherapy is increasingly being explored for resectable, locally advanced oral squamous cell carcinoma, and yet real-world evidence regarding its effectiveness and safety remains limited. In addition, a proportion of patients do not proceed to surgery after neoadjuvant treatment, and outcomes in this subgroup are insufficiently characterized. Our retrospective cohort study involved 39 consecutive patients with resectable, locally advanced oral squamous cell carcinoma, treated between September 2023 and June 2025 at two affiliated hospitals of Guangzhou Medical University with a programmed cell death 1 inhibitor combined with paclitaxel and cisplatin. Tumor response was documented using standardized clinical examinations, case report form (CRF)-based monitoring, radiological assessment primarily according to RECIST v1.1, and supplementary iRECIST review where applicable. The primary endpoint was objective response rate; secondary endpoints included pathologic complete response among patients undergoing surgery, 2-year disease-free survival, overall survival, and treatment-related adverse events. Of the 39 patients, 35 completed radiological evaluation; nine achieved a complete response, and 14 achieved a partial response, yielding an objective response rate of 65.7% (95% confidence interval 45.8–79.4). Twenty patients proceeded to surgery, and 10 achieved pathologic complete response (50.0%; 95% confidence interval 29.9–70.1). At a median follow-up of 16 months, six disease-free survival events occurred and no deaths were observed. The estimated 2-year disease-free survival was 84.4% (95% confidence interval, 60.9–89.3). Disease-free survival did not differ significantly between patients managed with surgery and those managed without surgery; however, these comparisons are exploratory and should be interpreted cautiously given the limited sample size and low event rate. Overall, neoadjuvant immunotherapy combined with paclitaxel and cisplatin demonstrated substantial antitumor activity, encouraging pathologic complete response rates, and clinically manageable toxicity in routine practice. Our findings provide a basis for future prospective studies of this regimen. Surgery remains the cornerstone of curative treatment for resectable locally advanced oral squamous cell carcinoma. Meanwhile, for carefully selected treatment responders, further investigations into response-adapted surgical de-escalation strategies are warranted.