# Sequencing of Immunotherapy and Outcomes in Operable Clinical Stage III Melanoma: A National Cohort Study

## TL;DR

This study examines how using immunotherapy before surgery affects survival in stage III melanoma patients, finding no overall survival difference but a benefit for those with more advanced disease.

## Contribution

The study reveals that neoadjuvant immunotherapy is associated with improved survival in patients with advanced N category stage III melanoma.

## Key findings

- Patients with N2/N3 disease had improved 3-year OS with NIT versus AIT-only.
- There was no significant difference in 3-year OS between NIT and AIT groups overall.
- NIT was more commonly given to patients with advanced N category disease.

## Abstract

The impact of neoadjuvant immunotherapy (NIT) on overall survival (OS) in patients with resectable stage III melanoma remains unknown. We sought to identify factors associated with receipt of NIT and survival outcomes in patients with clinical stage III melanoma undergoing surgery.

The National Cancer Database (2016–2020) was used to identify patients with clinical stage III melanoma who underwent surgery and received either NIT or adjuvant immunotherapy (AIT) only. Multivariable regression, Kaplan–Meier, and Cox proportional hazard methods were used to analyze variables of interest.

Patients with clinical N3 disease had 2.5 times the odds of NIT compared to those with N1 disease (95% CI 1.74–3.49). There was no difference in 3‐year OS between the two cohorts: 79% (95% CI 73%–85%) for NIT patients and 75% (95% CI 73%–76%) for AIT patients (p = 0.078). Patients with N2/N3 disease had improved 3‐year OS of 79% with NIT versus 71% for AIT‐only (HR 0.61, 95% CI 0.38–0.97, p = 0.037).

NIT is given more selectively to clinical stage III patients with more advanced N category disease. Despite significant differences in N category between groups, there was no difference in OS observed at 3 years, and NIT was associated with a survival advantage among N2/N3 patients.