Clinical, Dermatoscopic, Histological and Molecular Predictive Factors of Melanoma Response to Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-analysis

Immune checkpoint inhibitors have transformed the treatment of metastatic melanoma; however, reliable prognostic markers remain limited. In this systematic review and meta-analysis, reported in accordance with PRISMA, a literature search of MEDLINE, Web of Science, and CENTRAL (2018–2025) was conducted to evaluate clinical, laboratory, histologic, and molecular factors associated with overall survival and progression-free survival in adult melanoma patients receiving immunotherapy. Older age was associated with worse overall survival, whereas sex showed no consistent prognostic value. Poor performance status and elevated LDH emerged as strong and consistent adverse prognostic factors, while a higher body mass index was associated with improved survival. Greater disease burden (advanced stage, multiple metastatic sites, and brain metastases) was also linked to poorer outcomes. Among histologic and molecular features, ulceration and acral subtype were associated with worse survival, whereas high tumor mutational burden correlated with improved progression-free survival. In addition, cutaneous immune-related adverse events were favorable prognostic indicators, while detectable circulating tumor DNA (ctDNA) in blood was associated with markedly worse prognosis. In contrast, liver metastases and PD-L1 expression were not clearly associated with survival. Overall, these findings underscore the multifactorial determinants of immunotherapy outcomes and support the development of integrated prognostic models to improve patient stratification and optimize treatment strategies.