Perioperative immunotherapy in locally advanced head and neck squamous cell carcinoma: an Austrian consensus-based treatment algorithm

Curative treatment strategies for locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) have long relied on surgery and risk-adapted radio(chemo)therapy, with limited improvements in long-term outcomes. Although immune checkpoint inhibitors have transformed the management of recurrent or metastatic disease, earlier attempts to incorporate immunotherapy into definitive or adjuvant treatment concepts for LA-HNSCC were unsuccessful. Recently, two randomized phase III trials, KEYNOTE-689 and NIVOPOSTOP, demonstrated for the first time that perioperative integration of immune checkpoint inhibition can improve clinically relevant outcomes in the curative setting. KEYNOTE-689 established a perioperative pembrolizumab-based strategy combining neoadjuvant and adjuvant immunotherapy with standard multimodal treatment, resulting in a significant improvement in event-free survival. NIVOPOSTOP showed that the addition of adjuvant nivolumab to postoperative cisplatin-based radiochemotherapy improves disease-free survival in patients with resected high-risk disease. While overall survival data from both studies do not yet have sufficient follow-up, consistent favorable trends have been observed, supporting the clinical relevance of these approaches. The practical implementation of perioperative immunotherapy is complex and requires strict patient selection, reliable biomarker assessment, and careful coordination of treatment sequencing to avoid delays in definitive local therapy. On the basis of a structured, multidisciplinary consensus process involving Austrian head and neck cancer centers and refined through national interdisciplinary discussions, we developed a nationwide, practice-oriented treatment algorithm for perioperative immunotherapy in LA-HNSCC. This consensus-based algorithm aims to support safe, timely, and evidence-based integration of perioperative immunotherapy into routine clinical practice.