Five-year survival after introduction of adjuvant treatment in stage III melanoma: A nationwide registry-based study

BACKGROUND: In patients with stage III cutaneous melanoma, adjuvant treatments with PD-1 and BRAF+MEK inhibitors were approved based on improved recurrence-free survival. However, as the treatments have significant side effects and costs, the effect on overall survival remains a matter of great importance. METHODS: Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with stage IIIB-D melanoma in 2016-2020. Patients under the age of 75 years, that had a positive sentinel lymph node (SLN) were included. Patients were divided into two cohorts, depending on if the SLN biopsy was performed before or from September 2018 (pre- and post-cohort), based on the timepoint when adjuvant treatment was introduced. Patients were followed for survival until the end of 2024. RESULTS: The five-year overall survival rates were, 67.3 % (95 % CI 62.0-72.9) in the pre-cohort (n = 287) and 70.1 % (95 % CI 65.3-75.2) in the post-cohort (n = 349), with hazard ratio adjusted for age, sex and tumor stage of 0.96 (95 % CI 0.73-1.27), P=0.791. In the post-cohort 72.8 % received adjuvant treatment, the majority with PD-1 inhibitors where treatment exposure was highest in those < 60 years (80.2 %), males (78.3 %) and those having thicker primary melanomas (75.4 %). No significant overall or melanoma-specific survival differences were observed when comparing the pre- and the post-cohort in different subgroups. CONCLUSIONS: In this nationwide, population and registry-based study there was no overall survival benefit observed five years after the introduction of adjuvant treatment for patients with stage III melanoma. These findings encourage a careful assessment of the current recommendation on adjuvant treatment.