Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model.

Patients with stage I/IIA cutaneous melanoma (CM) are currently not eligible for adjuvant therapies despite uncertainty in relapse risk. Here, we studied the ability of a recently developed model which combines clinicopathologic and gene expression variables (CP-GEP) to identify stage I/IIA melanoma patients who have a high risk for disease relapse. Archival specimens from a cohort of 837 consecutive primary CMs were used for assessing the prognostic performance of CP-GEP. The CP-GEP model combines Breslow thickness and patient age, with the expression of eight genes in the primary tumour. Our specific patient group, represented by 580 stage I/IIA patients, was stratified based on their risk of relapse: CP-GEP High Risk and CP-GEP Low Risk. The main clinical end-point of this study was five-year relapse-free survival (RFS). Within the stage I/IIA melanoma group, CP-GEP identified a high-risk patient group (47% of total stage I/IIA patients) which had a considerably worse five-year RFS than the low-risk patient group; 74% (95% confidence interval [CI]: 67%-80%) versus 89% (95% CI: 84%-93%); hazard ratio [HR] = 2.98 (95% CI: 1.78-4.98); P < 0.0001. Of patients in the high-risk group, those who relapsed were most likely to do so within the first 3 years. The CP-GEP model can be used to identify stage I/IIA patients who have a high risk for disease relapse. These patients may benefit from adjuvant therapy.

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Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement Dr. Eggermont reports receiving honoraria from Actelion, Agenus, Bayer, BIOCAD, Biovent, BMS, CatalYm, Celldex, Ellipses, Forbion, Gilead, GSK, HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, MedImmune, Merck GmbH, MSD, Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SkylineDx and Stellas over the past five years; having equity stakes in SkylineDx and THERANOVIR and speaker engagements with BIOCAD, MSD and Novartis. Dr. Bellomo reports equity stakes in SkylineDx and Synlogic. Dr. Hieken reports receiving research funding from Genentech and Roche through Mayo Clinic. Dr. Sluzevich reports receiving research funding from Merck through Mayo Clinic. Dr. Pernaciaro reports receiving honoraria from Myriad Genetics and travel, accommodations and expenses paid for by Myriad Genetics. Ms. Tjien-Fooh, Ms. Rentroia-Pacheco, Ms. Wever, Dr. van Vliet, and Dr. Dwarkasing reports equity stakes in SkylineDx. Dr. Bellomo, Ms. Tjien-Fooh, Ms. Rentroia-Pacheco, Ms. Wever, Dr. van Vliet, and Dr. Dwarkasing reports being employees of SkylineDx. Dr. Bellomo and Dr. Meves report patents pending for gene signatures for predicting melanoma metastasis. All remaining authors have no conflict of interest to declare.