Real-World Outcomes for Patients with Clinically Node-Positive Melanoma Undergoing Neoadjuvant Immunotherapy and Nodal Dissection

Abstract Background Neoadjuvant immunotherapy (nIO) followed by a therapeutic lymph node dissection (TLND) for patients with clinically node-positive melanoma is supported by level 1 evidence. Our aim was to assess the association of pathologic response (PR) and nIO regimen with survival among patients with clinical stage III melanoma undergoing nIO and TLND. Methods Our study included patients treated with nIO followed by a TLND from a large academic institution between 2016 and 2024. The pathologic response was assessed using established guidelines. Differences in extent of PR (PR) by nIO regimen were examined. Disease-free survival (DFS) and overall survival (OS) by PR and nIO regimen were assessed. Results The study included 121 patients (78.5% treated with combination nIO; 21.5% treated with single-agent anti-PD-1). The pCR rate was 64.2% for combination therapy and 53.8% for monotherapy ( P =0.11). In univariable analysis, patients who received combination therapy had a 2-year DFS similar to patients treated with single-agent anti-PD-1 (86.5% vs 85.1%, respectively; P =0.43). Patients with a pCR had a 2-year DFS of 94.4% versus 57.3% among those with pathologic non-response (pNR) ( P <0.001). In multivariable analysis, PR was associated with DFS, but the nIO regimen was not. Our findings showed similar results for OS, with a 2-year OS of 98.1% for patients with pCR compared with 94.7% for those with pNR ( P =0.01). Conclusions Consistent with clinical trial data, the findings in this study support PR as a strong predictor of survival in this patient population. Studies investigating the de-escalation of surgical and systemic treatment based on PR as well as biomarkers of patients who can achieve a pCR after monotherapy alone are warranted.