Effect of neoadjuvant therapy on survival outcomes in patients with melanoma: a systematic review and meta-analysis

Melanoma is the most aggressive type of skin cancer, and its advanced cases often have a poor prognosis due to early metastasis. In recent years, neoadjuvant therapy (NT) has demonstrated potential benefits in treating solid tumours. However, its efficacy and safety in treating melanoma remain inconclusive. This study aimed to evaluate the complete response (CR), survival outcomes, and safety of NT in patients with melanoma.

In this systematic review and meta-analysis, Cochrane, Web of Science, Embase, and PubMed were searched up to 24 February 2025, and the Clinical Trial Registry was also search to identify additional eligible studies. Studies were included if they involved patients with melanoma receiving NT, with or without a comparator group. Both randomised controlled trials and non-randomised studies were eligible. In comparative studies, only those with adjuvant therapy or surgery alone as the comparator were included. Regardless of study design, all analyses were centred on the NT groups. Two reviewers separately screened the literature, extracted data, and evaluated the risk of bias. The quality of the included studies was appraised using National Institutes of Health study quality assessment tool (NIH-QAT). Data analysis was conducted through Stata 15.0 and R 4.4.1. After heterogeneity analysis of Cochrane's Q test and I ² statistics, single-arm and pairwise meta-analysis was separately conducted. Sensitivity analysis, subgroup analysis, meta-regression were conducted to explore the source and influence of heterogeneity. Publication bias was identified by Egger's test, funnel plot and explored by trim-and-fill analysis. The primary outcome was pathological complete response (pCR) and radiological complete response (rCR), and the secondary outcomes included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). The study is registered with PROSPERO, CRD420251021368.

A total of 43 studies involving 2821 patients with melanoma who received NT were included. Based on the NIH-QAT, the overall quality of the included studies was considered good. Meta-analysis showed that the pooled pCR was 33% (95% CI: 27%-39%, I ² = 77.0%), the rCR was 11% (95% CI: 5%, 16%, I ² = 68.0%), and the incidence of grade ≥3 AEs was 33% (95% CI: 23%-44%, I ² = 95.5%). Regarding survival outcomes, the pooled OS rate (OSR) was 81% (95% CI: 76%, 86%, I ² = 85.3%), and the PFS rate (PFSR) was 60% (95% CI: 52%-68%, I ² = 91.7%). Subgroup analyses indicated that follow-up duration, type of intervention and study design may contribute to the observed heterogeneity. Compared with adjuvant-only therapy (AT), NT was associated with significantly improved PFS (HR = 0.58, 95% CI: 0.39-0.87, I ² = 72.5%) and OS (HR = 0.64, 95% CI: 0.41-0.99, I ² = 0%), with no significant difference in the risk of severe AEs (RR = 1.15, 95% CI: 0.93-1.43, I ² = 0%).

Current evidence suggests that NT in patients with melanoma is associated with a favourable CR and promising survival benefits without increasing the risk of severe AEs. Compared to AT, NT demonstrates potential advantages in reducing the risks of disease progression and death. However, the results of this study s should be considered exploratory since the majority of included studies are single-arm or observational studies. Further high-quality randomised trials are needed to confirm the long-term efficacy and safety of NT.

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