Treatment trends and survival outcomes in clinical stage III melanoma: A real-world analysis of NCDB data (2006-2022).

Abstract

e21537 Background: The treatment paradigm for clinical Stage III melanoma has significantly evolved with the adoption of immunotherapy and targeted therapies. While clinical trials highlight the efficacy of resection combined with systemic therapies, real-world data on patterns of care and outcomes remain limited. Methods: This retrospective cohort study utilized the National Cancer Database (NCDB) to analyze 14,406 patients with clinical Stage III melanoma diagnosed from 2006 to 2022. Patients were categorized by treatment modality: surgery only, resection plus immune checkpoint inhibitor (ICI), resection plus targeted therapy, and neoadjuvant strategies (immunotherapy or targeted therapy). Trends in treatment utilization were assessed over time. Overall survival (OS) was evaluated using Kaplan-Meier analysis, and hazard ratios (HR) were calculated with multivariable Cox proportional hazards regression. Results: Among 14,406 patients (median age: 61; 64.2% male), the use of surgery alone declined sharply from 66.5% in 2014 to 16.5% in 2022, as resection combined with ICIs emerged as the predominant treatment modality. Neoadjuvant therapies, initially used in less than 1% of cases, saw a noticeable increase after 2015, reaching 12.7% by 2022. Resection plus ICI was associated with significantly improved OS compared to surgery alone (HR 0.73; 95% CI, 0.68–0.79; p < 0.001). Similarly, neoadjuvant immunotherapy demonstrated a comparable OS benefit (HR 0.65; 95% CI, 0.52–0.83; p < 0.001). The median OS was 7.8 years for surgery alone (p < 0.001), 15.8 years for resection plus ICI (p < 0.001), and was not reached for neoadjuvant immunotherapy. Factors associated with worse OS included lymphovascular invasion (HR 1.34; 95% CI, 1.23–1.46; p < 0.001) and N3 disease (HR 1.65; 95% CI, 1.51–1.80; p < 0.001). Conclusions: Real-world data highlights the rapid adoption of resection combined with ICI as the standard of care for Stage III melanoma, driven by its significant survival advantage over surgery alone. The promising outcomes of neoadjuvant immunotherapy, with comparable OS, highlights the need for further research to refine treatment sequencing and identify optimal patient selection criteria. Hazard ratios of treatment modalities for stage III melanoma. Treatment Modality N Hazard Ratio (95% CI) P-value Surgery Only 4763 1 [Reference] N/A Resection Plus ICI 4137 0.73 (0.68, 0.79) <0.001 Resection + Targeted Therapy 697 1.14 (1.02, 1.28) 0.024 Neoadjuvant Immunotherapy 273 0.65 (0.52, 0.83) <0.001 Neoadjuvant Targeted Therapy 46 1.03 (0.68, 1.58) 0.883