{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:00:42Z","timestamp":1789999242783,"version":"4.0.1"},"reference-count":85,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The therapeutic management of cutaneous malignancies\u2014cutaneous melanoma, cutaneous squamous-cell carcinoma (cSCC), basal-cell carcinoma (BCC) and Merkel-cell carcinoma (MCC)\u2014has shifted toward multimodal, stage-adapted treatment integrating surgery, radiotherapy, molecularly targeted therapy and immune checkpoint inhibition. Methods: We conducted a structured narrative review with a structured literature search of PubMed\/MEDLINE, Scopus and Web of Science (January 2015\u20136 September 2026), prioritising current clinical practice guidelines, randomised controlled trials and phase II\u2013III studies; landmark older trials were included separately. Synthesis: Surgery with adequate histological margins, including Mohs micrographic surgery where appropriate, remains definitive for localised disease. In resectable macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab with response-driven postoperative management improved event-free survival versus adjuvant nivolumab in NADINA. SWOG S1801 independently demonstrated an event-free-survival advantage for perioperative pembrolizumab over adjuvant-only pembrolizumab in resectable stage III\u2013IV melanoma. In advanced melanoma, dual immune-checkpoint strategies and BRAF\/MEK inhibition require patient-specific sequencing; in the European Union, nivolumab plus relatlimab is authorised for first-line advanced melanoma with tumour-cell PD-L1 expression &lt;1%. In high-risk cSCC after surgery and radiotherapy, adjuvant cemiplimab improved disease-free survival. In advanced BCC, Hedgehog-pathway inhibitors remain the principal first systemic option, with anti-PD-1 therapy after HHI failure or intolerance. Clinical implications: Molecular testing should be indication-driven: BRAF V600 is a validated treatment-selecting biomarker, while broader NGS profiling (including NRAS, KIT, NF1, TERT and co-occurring alterations), PD-L1, tumour mutational burden and circulating tumour DNA have context-dependent, supportive or investigational roles. Conclusions: The major unresolved issues are optimal sequencing, response-adapted perioperative treatment, resistance, biomarker validation and treatment of transplant, frail and other under-represented populations.<\/jats:p>","DOI":"10.3390\/cancers18183029","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contemporary Multimodal Management of Cutaneous Malignancies: Surgery, Radiotherapy, Systemic Therapy, Molecular Targeting and Immunotherapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9512-8677","authenticated-orcid":false,"given":"Dariusz","family":"Kowalczyk","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Kalisz, 62-800 Kalisz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2334-1093","authenticated-orcid":false,"given":"Jolanta","family":"Jaworek","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Care, Faculty of Medicine, University of Applied Sciences in Tarnow (Akademia Tarnowska), ul. Mickiewicza 8, 33-100 Tarnow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Ciborek","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Kalisz, 62-800 Kalisz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-0223","authenticated-orcid":false,"given":"Pawel Antoni","family":"Kolodziejski","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6905","authenticated-orcid":false,"given":"Ewa","family":"Pruszy\u0144ska-Oszma\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Krauss","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Kalisz, 62-800 Kalisz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1056\/NEJMoa1103782","article-title":"Improved survival with vemurafenib in melanoma with BRAF V600E mutation","volume":"364","author":"Chapman","year":"2011","journal-title":"N. 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