Contemporary Multimodal Management of Cutaneous Malignancies: Surgery, Radiotherapy, Systemic Therapy, Molecular Targeting and Immunotherapy

Abstract

Simple Summary Cutaneous malignancies include melanoma, cutaneous squamous-cell carcinoma, basal-cell carcinoma and Merkel-cell carcinoma. Their management has changed rapidly in recent years owing to the increasing use of immune checkpoint inhibitors, targeted therapies and perioperative systemic treatment. This review summarizes the current multimodal treatment landscape, including surgery, radiotherapy, immunotherapy, molecularly targeted therapy and selected reconstructive strategies. Particular attention is given to recent practice-changing evidence, including neoadjuvant immunotherapy in resectable stage III melanoma, adjuvant cemiplimab in high-risk cutaneous squamous-cell carcinoma, anti-LAG-3 therapy in advanced melanoma and Hedgehog-pathway inhibition in advanced basal-cell carcinoma. The review also discusses predictive biomarkers, treatment sequencing, resistance mechanisms and special populations such as transplant recipients. Overall, treatment selection is increasingly determined by tumour type, stage, resectability and validated biomarkers, while several important questions concerning optimal sequencing, long-term outcomes and under-represented patient groups remain unresolved.