Investigating Risk Factors for Delayed Melanoma Recurrence Beyond 5 Years Post-Primary Tumor Diagnosis.
11 affiliations
- 1Department of Dermatology, University Hospital of Basel, Basel, Switzerland.
- 2Robert Larner, M.D. College of Medicine at the University of Vermont, Burlington, Vermont, USA.
- 3Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
- 4Faculty of Science, Technology, Engineering & Mathematics, The Open University, Milton Keynes, UK.
- 5Department of Orthopedics and Trauma Surgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- 6Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
- 7Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- 8Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary.
- 9Department of Dermatology and Allergology, Szent-Györgyi Albert Medical School, University of Szeged, Szeged, Hungary.
- 10School of Mathematics and Statistics, Faculty of Science, Technology, Engineering and Mathematics, The Open University, Milton Keynes, UK.
- 11Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, UK.
Abstract
Background
Patients undergoing treatment for cutaneous melanoma are generally considered cured after a period of 5 years, since most recurrences manifest within three to 5 years. However, some patients can present with a delayed recurrence of melanoma beyond a 10-year timeframe.Objective
To identify clinicopathologic factors associated with survival in patients with cutaneous melanoma who developed metastatic recurrence at least 5 years after primary diagnosis.Methods
We conducted a retrospective single-center cohort study of 30 patients with cutaneous melanoma developing metastatic recurrence at least 5 years post-diagnosis. The cohort contained 18 women and 12 men (mean age 50.2; range 25-76). Variables included age, sex, BRAF status, site, melanoma subtype, Breslow thickness, ulceration, Clark level, regression, and recurrence localization. Overall survival (OS), progression-free survival (PFS), and post-recurrence survival (PRS) were evaluated via Cox proportional hazards models.Results
Mean OS, PFS, and PRS were 168.7, 130.4, and 43.7 months, respectively. Eight patients (27%) died. Tumors averaged 2.61 mm Breslow thickness; 50.0% were BRAF-mutant, 53.3% ulcerated, and 50.0% truncal. Recurrences were locoregional (cutaneous, subcutaneous, in-transit, nodal) in eight (26.7%) and distant in 21 (70.0%); one lacked data. Female sex predicted better univariate OS (HR 0.055, 95% CI 0.01-0.47; p = 0.008) and multivariate PFS (HR 0.364, 95% CI 0.14-0.93; p = 0.035). Increasing age predicted shorter multivariate PFS (HR 1.072, 95% CI 1.03-1.12; p = 0.001). Histologic regression (HR 3.557, 95% CI 1.04-12.17; p = 0.043) and BRAF status (HR 0.413, 95% CI 0.18-0.94; p = 0.034) independently impacted PFS. Kaplan-Meier showed longer OS and PFS in women, and longer PFS in patients younger than 50 years.Conclusions
Delayed recurrence can manifest over a decade post-diagnosis. Female sex and younger age correlate with favorable survival. These findings underscore the necessity of continued clinical vigilance and patient counseling beyond 10 years, although larger cohorts are needed to validate late-recurrence risk stratification.
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BibTeX
@article{itin2026investigating,
title = {{Investigating Risk Factors for Delayed Melanoma Recurrence Beyond 5 Years Post-Primary Tumor Diagnosis.}},
author = {Kaspar Itin and Rebecca Lapides and Soumya Paria and Babak Saravi and Alina M Torrez and Lara Valeska Maul and Michael Wang-Evers and Alexander A Navarini and Dieter Manstein and Beata Kun and Leticia Szadai and Judit Olàh and Eszter Baltas and Rolland Gyulai and Peter Hollo and Grzegorz Sarek and Istvan B Németh and Kaustubh Adhikari and Elisabeth Roider},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72389},
url = {https://europepmc.org/article/MED/42952107},
note = {CC BY},
}
RIS
TY - JOUR
TI - Investigating Risk Factors for Delayed Melanoma Recurrence Beyond 5 Years Post-Primary Tumor Diagnosis.
AU - Kaspar Itin
AU - Rebecca Lapides
AU - Soumya Paria
AU - Babak Saravi
AU - Alina M Torrez
AU - Lara Valeska Maul
AU - Michael Wang-Evers
AU - Alexander A Navarini
AU - Dieter Manstein
AU - Beata Kun
AU - Leticia Szadai
AU - Judit Olàh
AU - Eszter Baltas
AU - Rolland Gyulai
AU - Peter Hollo
AU - Grzegorz Sarek
AU - Istvan B Németh
AU - Kaustubh Adhikari
AU - Elisabeth Roider
PY - 2026
DA - 2026/10/28
JO - Cancer medicine
DO - 10.1002/cam4.72389
UR - https://europepmc.org/article/MED/42952107
AB - Background Patients undergoing treatment for cutaneous melanoma are generally considered cured after a period of 5 years, since most recurrences manifest within three to 5 years. However, some patients can present with a delayed recurrence of melanoma beyond a 10-year timeframe.Objective To identify clinicopathologic factors associated with survival in patients with cutaneous melanoma who developed metastatic recurrence at least 5 years after primary diagnosis.Methods We conducted a retrospective single-center cohort study of 30 patients with cutaneous melanoma developing metastatic recurrence at least 5 years post-diagnosis. The cohort contained 18 women and 12 men (mean age 50.2; range 25-76). Variables included age, sex, BRAF status, site, melanoma subtype, Breslow thickness, ulceration, Clark level, regression, and recurrence localization. Overall survival (OS), progression-free survival (PFS), and post-recurrence survival (PRS) were evaluated via Cox proportional hazards models.Results Mean OS, PFS, and PRS were 168.7, 130.4, and 43.7 months, respectively. Eight patients (27%) died. Tumors averaged 2.61 mm Breslow thickness; 50.0% were BRAF-mutant, 53.3% ulcerated, and 50.0% truncal. Recurrences were locoregional (cutaneous, subcutaneous, in-transit, nodal) in eight (26.7%) and distant in 21 (70.0%); one lacked data. Female sex predicted better univariate OS (HR 0.055, 95% CI 0.01-0.47; p = 0.008) and multivariate PFS (HR 0.364, 95% CI 0.14-0.93; p = 0.035). Increasing age predicted shorter multivariate PFS (HR 1.072, 95% CI 1.03-1.12; p = 0.001). Histologic regression (HR 3.557, 95% CI 1.04-12.17; p = 0.043) and BRAF status (HR 0.413, 95% CI 0.18-0.94; p = 0.034) independently impacted PFS. Kaplan-Meier showed longer OS and PFS in women, and longer PFS in patients younger than 50 years.Conclusions Delayed recurrence can manifest over a decade post-diagnosis. Female sex and younger age correlate with favorable survival. These findings underscore the necessity of continued clinical vigilance and patient counseling beyond 10 years, although larger cohorts are needed to validate late-recurrence risk stratification.
SN - 2045-7634
ER -