Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis

Introduction Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. Methods A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020–2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I 2 statistic. Results The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9–88.2) for the former and 82% (75.2–87.2) for the latter ( P =.751), and the respective pooled OS was 92.3% (87.5–95.3) and 91.4% (80.3–96.5) ( P =.839). The pooled pCR rate was 41.7% (95% CI 5.4–48.4; I 2 =.0) for RAS and 19.8% (95%CI 13.3–29.6; I 2 =.62) for BPS ( P =.001), while the MPR was not significantly different (59.6%, versus 48.5%, P =.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. Conclusions RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.