Impacto da imunoterapia neoadjuvante nos desfechos patológicos e na sobrevida de pacientes com melanoma cutâneo ressecável em estágios IIIe IV: uma revisão sistemática

Abstract

Cutaneous melanoma is the most biologically aggressive and lethal form of skin malignancy, particularly in resectable stage III and IV disease, in which the risk of recurrence remains significant even after surgical treatment. In this context, immunotherapy based on immune checkpoint inhibitors has promoted substantial advances in the management of advanced disease, emerging as an innovative therapeutic alternative. More recently, the neoadjuvant administration of these agents has demonstrated the potential to induce more robust antitumor responses, favoring preoperative tumor regression and early systemic disease control. The present study consists of a systematic review of the literature, conducted according to the PRISMA guidelines, aiming to critically analyze the scientific evidence regarding the impact of neoadjuvant immunotherapy on pathological and survival outcomes in patients with resectable stage III and IV cutaneous melanoma. A total of 11 studies were included, comprising 1,091 patients treated with different therapeutic regimens involving pembrolizumab, nivolumab, and ipilimumab, administered as monotherapy or combination therapy. The findings demonstrated expressive rates of pathological complete response, reaching up to 68% in combined regimens, and major pathological response of up to 73%, particularly in combined regimens, in addition to consistent benefits in recurrence-free survival, event-free survival, with EFS of up to 77.3% in the neoadjuvant group versus 55.7% in the adjuvant group (NADINA), and distant metastasis-free survival when compared with exclusively adjuvant strategies. Although the incidence of severe adverse events was higher in combination regimens, the toxicity profile proved to be clinically manageable. It is concluded that neoadjuvant immunotherapy represents a promising therapeutic strategy with the potential to redefine the treatment paradigm for advanced resectable cutaneous melanoma, although additional studies are still required to consolidate its incorporation into clinical practice.