Timing of surgery after neoadjuvant immunochemotherapy in head and neck squamous cell carcinoma: Current evidence, surgical implications, and a research agenda.

Abstract / Summary

Perioperative immune checkpoint blockade is rapidly moving into routine care for resectable head and neck squamous cell carcinoma (HNSCC), making timing of surgery after neoadjuvant immunotherapy (NAI) and neoadjuvant immunochemotherapy (NAIC) increasingly important clinical question rather than a purely theoretical one. Yet the literature remains dominated by studies that report feasibility or absence of delay, not by evidence that defines an optimal interval from treatment completion to surgery. Both immune-only and chemoimmunotherapy regimens are addressed, as their timing implications differ. To synthesize the current evidence regarding surgery timing after neoadjuvant immunotherapy and immunochemotherapy in HNSCC, with dedicated attention to oral squamous cell carcinoma (OSCC), and to propose a practical research-informed framework for current clinical use. This focused narrative review used targeted searches of PubMed/MEDLINE, Google Scholar, and reference lists of relevant reviews and primary studies through April 30, 2026. Priority was given to publications that explicitly reported interval to surgery, surgical delay, perioperative feasibility, pathologic response, complications, or OSCC-specific timing considerations. Consensus documents were included only to contextualize procedural guidance and were not treated as comparative timing evidence. We did not identify a systematic review whose primary aim was to define the optimal timing of surgery after neoadjuvant immunochemotherapy in HNSCC or OSCC. Previous reviews consistently show that neoadjuvant immunotherapy or chemoimmunotherapy is generally feasible and usually does not cause major surgical delay. Across prospective studies, surgery was commonly scheduled within approximately 1 to 4 weeks after the last neoadjuvant treatment, although interval definitions were heterogeneous. OSCC studies tend to use shorter intervals, often around 1 to 3 weeks. The strongest timing-specific evidence currently comes from a 2026 HNSCC study showing that surgery performed more than 3 weeks after neoadjuvant immunochemotherapy was associated with lower pathologic response, higher complication risk, and shorter disease-free survival. However, this finding remains observational and requires prospective validation. Current evidence supports surgical feasibility after neoadjuvant immunotherapy and immunochemotherapy in HNSCC but does not establish a universally validated optimal interval. For many PD-1-based immunochemotherapy regimens, avoiding unnecessary delay beyond 3 weeks after treatment completion appears evidence-aligned when toxicity recovery, wound-healing considerations, and operative logistics permit, but this position remains provisional and requires prospective validation. Immune-only regimens may permit earlier surgery in selected patients, whereas anti-angiogenic combinations require regimen-specific washout and wound-healing considerations. Future trials should prespecify timing strata, standardize interval definitions, and integrate surgical, pathological, and oncologic endpoints.

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