Survival after introduction of adjuvant treatment in stage III melanoma: a nationwide registry-based study

Abstract

Abstract Background Adjuvant treatments with PD-1 and BRAF+MEK inhibitors statistically significantly prolong recurrence-free survival in stage III cutaneous melanoma. Yet, the effect on overall survival is still unclear. Based on recurrence-free survival outcomes, these treatments have been approved and widely implemented. The treatments have considerable side effects and costs, and overall survival effect remains a highly anticipated outcome. Methods Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with stage III melanoma between 2016 and 2020. The patients were divided depending on if they were diagnosed before or from July 2018, based on the timepoint when adjuvant treatment was introduced in Sweden. Patients were followed up until the end of 2021. In this cohort study, melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox-regression analyses. Results There were 1371 patients diagnosed with stage III primary melanoma in Sweden in 2016-2020. The 2-year overall survival rates, comparing the 634 patients in the precohort and the 737 in the postcohort, were 84.3% (95% confidence interval [CI] = 81.4% to 87.3%) and 86.1% (95% CI = 83.4% to 89.0%), respectively, with an adjusted hazard ratio of 0.91 (95% CI = 0.70 to 1.19, P = .51). Further, no statistically significant overall or melanoma-specific survival differences were seen when comparing the precohort and the postcohort in different subgroups for age, sex, or tumor characteristics. Conclusions In this nationwide population-based and registry-based study, no survival benefit was detected in patients diagnosed before or after the implementation of adjuvant treatment in stage III melanoma. These findings encourage a careful assessment of the current recommendations on adjuvant treatment.