Case Report: The role of BRAF mutation in adjuvant and neoadjuvant treatment of melanoma patients: what is the optimal approach?

Background: IIID melanoma, its role in stage IIIA disease remains a matter of discussion. This subgroup is generally considered to be at lower risk of recurrence, whereas currently available treatments are associated with potential adverse events, some of which may be severe or irreversible. The presence of a BRAF mutation may assist in identifying patients at increased risk of relapse or those more likely to obtain benefit from adjuvant targeted therapy. Neoadjuvant immunotherapy with checkpoint inhibitors has recently emerged as a promising therapeutic strategy, demonstrating potential advantages over adjuvant treatment. Nevertheless, it may not represent the optimal approach for all patients and should be carefully evaluated on an individual basis, considering specific tumor characteristics such as mutational status to guide treatment selection. Case presentation: We report the clinical case of a patient with cutaneous melanoma initially diagnosed as stage IIIA, harboring BRAF V600E mutation, who did not receive any adjuvant therapy and developed locoregional recurrence within one year from diagnosis. The patient was subsequently treated with anti-PD-1 neoadjuvant immunotherapy but experienced disease progression at both local and distant sites. Then, targeted therapy was initiated, leading to a rapid clinical and radiological improvement. Conclusion: Despite significant advances in the treatment of stage III melanoma, both in the adjuvant and, more recently, neoadjuvant settings, some patient subgroups require more tailored approaches. In particular, the presence of BRAF V600 mutation may indicate a more aggressive disease and identify patients who could benefit more from targeted therapy or combined immune checkpoint inhibition than from anti-PD-1 monotherapy.