Neoadjuvant treatment for stage III and IV cutaneous melanoma

Background Cutaneous melanoma is amongst the most aggressive of all skin cancers. Neoadjuvant treatment is a form of induction therapy, given to shrink a cancerous tumour prior to the main treatment (usually surgery). The purpose is to improve survival and surgical outcomes. This review systematically appraises the literature investigating the use of neoadjuvant treatment for stage III and IV cutaneous melanoma. Objectives To assess the effects of neoadjuvant treatment in adults with stage III or stage IV melanoma according to the seventh edition American Joint Committee on Cancer (AJCC) staging system. Search methods We searched the following databases up to 10 August 2021 inclusive: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and four trials registers, together with reference checking and contact with study authors to identify additional studies. We also handsearched proceedings from specific conferences from 2016 to 2020 inclusive. Selection criteria Randomised controlled trials (RCTs) of people with stage III and IV melanoma, comparing neoadjuvant treatment strategies (using targeted treatments, immunotherapies, radiotherapy, topical treatments or chemotherapy) with any of these agents or current standard of care (SOC), were eligible for inclusion. Data collection and analysis We used standard Cochrane methods. Primary outcomes were overall survival (OS) and adverse effects (AEs). Secondary outcomes included time to recurrence (TTR), quality of life (QOL), and overall response rate (ORR). We used GRADE to evaluate the certainty of the evidence. Main results We included eight RCTs involving 402 participants. Studies enrolled adults, mostly with stage III melanoma, investigated immunotherapies, chemotherapy, or targeted treatments, and compared these with surgical excision with or without adjuvant treatment. Duration of follow‐up and therapeutic regimens varied, which, combined with heterogeneity in the population and definitions of the endpoints, precluded meta‐analysis of all identified studies. We performed a meta‐analysis including three studies. We are very uncertain if neoadjuvant treatment increases OS when compared to no neoadjuvant treatment (hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.15 to 1.21; 2 studies, 171 participants; very low‐certainty evidence). Neoadjuvant treatment may increase the rate of AEs, but the evidence is very uncertain (26% versus 16%, risk ratio (RR) 1.58, 95% CI 0.97 to 2.55; 2 studies,