{
  "abstract": "Despite recent adoption of perioperative therapy for high-risk melanoma, its overall survival (OS) benefit remains unclear, highlighting the need for biomarkers to identify patients likely to benefit from treatment. Detection of circulating tumor DNA (ctDNA) after definitive treatment predicts recurrence, and emerging molecular residual disease (MRD) assays may influence management. We validated a tissue-free MRD assay in 48 patients with clinical stage II to III melanoma treated with surgery (52% nonacral cutaneous, 31% acral, and 17% mucosal). The assay detects MRD through bioinformatic analysis of methylation signals across >20,000 epigenomic regions. Plasma samples (n = 281; 280 successfully reported) were prospectively collected before surgery, at day 28, and every 3 to 6 months thereafter. Associations among MRD detection, recurrence, and OS were analyzed. At a median follow-up of 34.6 months with 27 recurrence events, postoperative surveillance sensitivity for distant recurrence was 81% with 100% posttreatment specificity. The median lead time between MRD detection and radiographic recurrence was 70.5 days. Surveillance MRD detection was associated with increased recurrence risk [hazard ratio (HR), 26.55; 95% confidence interval (CI), 2.86-246.58; P = 0.004]. Similarly, MRD detection 28 days postoperatively independently predicted recurrence (HR, 11.70; 95% CI, 3.09-43.76; P < 0.001) and death (HR, 31.14; 95% CI, 5.37-221.1; P < 0.001). Tissue-free epigenomic MRD detection was sensitive, specific, and significantly associated with recurrence and melanoma-related death. These findings support the use of this assay in melanoma as a rapid, noninvasive approach for earlier identification of patients at high risk for recurrence, enabling refined treatment and surveillance strategies.Significance\n\nPrognostic tools for high-risk melanoma rely on baseline factors with limited dynamic risk assessment. A tissue-free MRD assay demonstrated high sensitivity and specificity for distant recurrence detection, identifying molecular relapse before radiographic recurrence. Postoperative MRD detection was strongly associated with recurrence and melanoma-related death, enabling refined treatment and surveillance strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.",
    "Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan.",
    "Department of Dermatologic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.",
    "Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.",
    "Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.",
    "Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kenjiro Namikawa",
      "orcid": "0000-0003-2763-7346"
    },
    {
      "affs": [
        0
      ],
      "name": "Dai Ogata",
      "orcid": "0000-0002-1335-7100"
    },
    {
      "affs": [
        0
      ],
      "name": "Eiji Nakano",
      "orcid": "0000-0001-7632-8182"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoya Yamazaki",
      "orcid": "0000-0002-9638-0428"
    },
    {
      "affs": [
        1
      ],
      "name": "Azusa Komada",
      "orcid": "0009-0000-1462-9211"
    },
    {
      "affs": [
        2
      ],
      "name": "Akira Takahashi",
      "orcid": "0000-0002-9304-7590"
    },
    {
      "affs": [
        3
      ],
      "name": "Shusuke Yoshikawa",
      "orcid": "0009-0002-6082-4696"
    },
    {
      "affs": [
        4
      ],
      "name": "Chiemi Notake",
      "orcid": "0009-0003-1998-7650"
    },
    {
      "affs": [
        4
      ],
      "name": "Ryuta Mitani",
      "orcid": "0009-0007-2132-1232"
    },
    {
      "affs": [
        5
      ],
      "name": "Takayuki Yoshino",
      "orcid": "0000-0002-0489-4756"
    },
    {
      "affs": [
        4
      ],
      "name": "Yoshiaki Nakamura",
      "orcid": "0000-0002-5241-6855"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dgvv4dhy1q7vj.bib",
  "cited_by": 0,
  "doi": "10.1158/2767-9764.crc-26-0388",
  "fulltext_url": "https://europepmc.org/articles/PMC13669714",
  "id": "dgvv4dhy1q7vj",
  "issns": [
    "2767-9764"
  ],
  "landing_url": "https://europepmc.org/article/MED/42831872",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cutaneous Melanoma Detection and Management"
    ]
  ],
  "openalex": "W7220385587",
  "pdf_url": "https://europepmc.org/articles/PMC13669714?pdf=render",
  "pmcid": "PMC13669714",
  "pmid": "42831872",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dgvv4dhy1q7vj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42831872",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42831872"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cutaneous Melanoma Detection and Management",
      "subfield": "oncology"
    }
  ],
  "title": "Melanoma Recurrence Prediction Using a Tissue-Free Epigenomic Molecular Residual Disease Assay: A Multicenter Prospective Observational Study (COSMOS-MEL01).",
  "title_text": "Melanoma Recurrence Prediction Using a Tissue-Free Epigenomic Molecular Residual Disease Assay: A Multicenter Prospective Observational Study (COSMOS-MEL01).",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/dgvv4dhy1q7vj",
  "venue": "Cancer research communications",
  "versions": []
}