Trends in the Use of Neoadjuvant Systemic Therapy for Head and Neck Squamous Cell Carcinoma

A paradigm shift is currently under way for the treatment of head and neck squamous cell carcinoma (HNSCC). Recent trials have demonstrated potential effectiveness of neoadjuvant systemic therapy (NST), including chemotherapy and immunotherapy; however, data on application of this approach are limited. To evaluate trends in the use of NST in patients with HNSCC from 2004 to 2022 and factors associated with treatment. This multicenter, retrospective cohort study used the National Cancer Database to identify 312 748 patients diagnosed with HNSCC from January 1, 2004, to December 31, 2022, who received definitive surgery. NST was defined as therapy administered at least 8 weeks before definitive surgery. Sociodemographic factors and clinical characteristics. Adjusted risk of receiving neoadjuvant immunotherapy and chemotherapy across the analyzed years. Among 312 748 patients (mean [SD] age, 63.3 [12.2] years; 218 218 [69.8%] male) who underwent surgery between 2004 and 2022, 1989 (0.6%) received NST, and among these, 1372 (69.0%) received neoadjuvant chemotherapy, 726 (36.5%) received neoadjuvant immunotherapy, and 109 (5.5%) received both. The first year of recorded neoadjuvant immunotherapy was 2007, with a use rate of 0.02%. Use began to increase in 2013 with a rate of 0.14%, peaking at 0.73% in 2019 but decreasing to 0.27% in 2022. From 2007 to 2022, the adjusted risk of receiving neoadjuvant immunotherapy increased by 22.5% per year (risk ratio [RR], 1.22; 95% CI, 1.19-1.26), whereas the adjusted risk of receiving chemotherapy decreased by −2.5% per year (RR, 0.97; 95% CI, 0.96-0.99). Sites with the largest increases in neoadjuvant immunotherapy use since 2013 were the hypopharynx (from 0.25% to 1.30%), gums and other oral cavity (from 0.19% to 0.58%), and tongue (from 0.18% to 0.27%). Patients who received neoadjuvant immunotherapy were more likely to have private insurance (342 [47.1%] vs 125 542 [40.2%]; P < .001), more likely to have stage IV disease (394 [54.3%] vs 100 565 [32.2%]; P < .001), and less likely to identify as Black (33 [4.5%] vs 21 384 [6.9%]; P = .01). In this retrospective cohort study of HNSCC, rates of neoadjuvant immunotherapy nearly doubled between 2013 and 2022, whereas neoadjuvant chemotherapy use significantly decreased from 2007 to 2022. These trends highlight the evolving therapeutic landscape for HNSCC and provide context for emerging data on neoadjuvant therapy.