Melanoma Recurrence Prediction Using a Tissue-Free Epigenomic Molecular Residual Disease Assay: A Multicenter Prospective Observational Study (COSMOS-MEL01).

@article{namikawa2026melanoma,
  title = {{Melanoma Recurrence Prediction Using a Tissue-Free Epigenomic Molecular Residual Disease Assay: A Multicenter Prospective Observational Study (COSMOS-MEL01).}},
  author = {Kenjiro Namikawa and Dai Ogata and Eiji Nakano and Naoya Yamazaki and Azusa Komada and Akira Takahashi and Shusuke Yoshikawa and Chiemi Notake and Ryuta Mitani and Takayuki Yoshino and Yoshiaki Nakamura},
  journal = {Cancer research communications},
  year = {2026},
  month = oct,
  doi = {10.1158/2767-9764.crc-26-0388},
  url = {https://europepmc.org/article/MED/42831872},
  note = {CC BY},
}

TY  - JOUR
TI  - Melanoma Recurrence Prediction Using a Tissue-Free Epigenomic Molecular Residual Disease Assay: A Multicenter Prospective Observational Study (COSMOS-MEL01).
AU  - Kenjiro Namikawa
AU  - Dai Ogata
AU  - Eiji Nakano
AU  - Naoya Yamazaki
AU  - Azusa Komada
AU  - Akira Takahashi
AU  - Shusuke Yoshikawa
AU  - Chiemi Notake
AU  - Ryuta Mitani
AU  - Takayuki Yoshino
AU  - Yoshiaki Nakamura
PY  - 2026
DA  - 2026/10/01
JO  - Cancer research communications
DO  - 10.1158/2767-9764.crc-26-0388
UR  - https://europepmc.org/article/MED/42831872
AB  - 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  Prognostic 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.
SN  - 2767-9764
ER  -