Abstract A092: Pathologic complete response and downstaging after neoadjuvant immunotherapy in head and neck squamous cell carcinoma
Abstract
Following the KEYNOTE-689 presentation in 2025, neoadjuvant immunotherapy has become an integral component of perioperative treatment for head and neck squamous cell carcinoma (HNSCC). As pathologic response is increasingly used to assess treatment efficacy, we evaluated rates of pathologic complete response (pCR) and clinical-to-pathologic stage changes among patients with HNSCC who did and did not receive neoadjuvant immunotherapy. Adults with HNSCC in the National Cancer Database (2004–2023) with complete clinical and pathologic staging were analyzed in Python 3.14.5. Patients were staged according to the applicable AJCC 6th, 7th, or 8th edition. Neoadjuvant immunotherapy was defined as immunotherapy administered before surgery. pCR was defined as pT0N0. Rates of pCR and clinical-to-pathologic stage change were compared between patients who did and did not receive neoadjuvant immunotherapy using univariate analysis. After excluding patients with unknown or same-day immunotherapy timing, 115,048 patients were included. Neoadjuvant immunotherapy was uncommon, with 388 patients (0.3%) receiving treatment. Receipt occurred in 0.2% of Hispanic patients (13/5,823), 0.3% of non-Hispanic Asian (12/3,663), non-Hispanic Black (30/8,758), and non-Hispanic White patients (327/94,132), and 0.2% of patients in all other racial groups combined (6/2,672). pCR occurred in 2.1% (8/388) of patients receiving neoadjuvant immunotherapy versus 0.3% (313/114,660) of those who did not. TNM downstaging occurred in 33.2% (129/388) versus 13.0% (14,893/114,660), respectively (OR 3.33, 95% CI 2.70–4.13). Among patients receiving neoadjuvant immunotherapy, downstaging occurred in 46.2% of Hispanic (6/13), 16.7% of non-Hispanic Asian (2/12), 36.7% of non-Hispanic Black (11/30), 33.0% of non-Hispanic White (108/327), and 33.3% of patients in all other racial groups combined (2/6). Patients receiving neoadjuvant immunotherapy also had lower rates of unchanged stage (32.7% vs. 49.7%) and upstaging (28.6% vs. 33.5%). Although pCR has historically been uncommon in HNSCC, it occurred more frequently among patients who received neoadjuvant immunotherapy than among those who did not. These findings suggest that neoadjuvant immunotherapy may increase the likelihood of pathologic complete response and clinical-to-pathologic downstaging. Audrey Rustad, Tariq Omer, Morgan Byrd, Andrew LoPolito, Brian B. Hughley, Nosayaba Osazuwa-Peters. Pathologic complete response and downstaging after neoadjuvant immunotherapy in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr A092.