Surgical Margin Reduction After Immunotargeted Neoadjuvant Therapy in Locally Advanced Hypopharyngeal Carcinoma: A Preliminary Margin Results from neoCHANCE-1 Trial

Importance Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive cancer with poor outcomes. Neoadjuvant therapy (NAT) may allow organ preservation, but determining safe surgical margins after NAT is a critical challenge. Objective To evaluate the safety of reduced surgical margins after neoadjuvant tislelizumab and afatinib in locally advanced HPSCC by comparing pathological margins to an upfront surgery control group. Design Prospective, single-center pilot cohort study. Setting Tertiary referral center in Western China. Participants Forty-one patients with locally advanced HPSCC; 32 received NAT (treatment group), and 9 served as an upfront surgery control group. Intervention or Exposures Treatment group: 2 cycles of neoadjuvant tislelizumab plus 6 weeks of afatinib. Control group: upfront surgery. Both groups underwent resection with a 1.5 cm naked-eye surgical margin. Main Outcome Measures Primary outcomes were minimal peripheral surgical margin (MPSM) and minimal deep surgical margin (MDSM). Secondary outcomes included radiological (RECIST v1.1) and pathological tumor response. Results The NAT group had a 20/32 (62.5%) radiological objective response rate and a 16/32 (50.0%) major pathological response rate [including 9/32 (28.13%) pathological complete response]. The mean MPSM was significantly greater in the treatment group versus control [3.38 mm vs 1.71 mm; 95% Confidence interval (CI): 0.10-3.24; P = .038]. The mean MDSM was also significantly greater in the treatment group versus control (2.09 mm vs 1.04 mm; 95% CI: 0.12-1.97; P = .029). Conclusions Combined immune-targeted NAT effectively downstages HPSCC. The significantly larger pathological margins observed support that reducing clinical surgical margins after this regimen is generally safe. Relevance This NAT regimen may allow for less extensive resections, facilitating laryngeal preservation and improving quality of life without compromising oncologic safety. Larger validation studies are needed.