Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary

I Johansson,D Tempel,J.T Dwarkasing,B Rentroia-Pacheco,J Mattsson,L Ny,R Olofsson Bagge

doi:10.1016/j.ejso.2021.11.010

Abstract

BackgroundIn patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) serves as an important technique to asses disease stage and to guide adjuvant systemic therapy. A model using clinicopathologic and gene expression variables (CP-GEP; Merlin Assay) has recently been introduced to identify patients that may safely forgo SLNB. Herein we present data from an independent validation cohort of the CP-GEP model in Swedish patients. MethodsArchival histological material (primary melanoma tissue) from a prospectively collected cohort of 421 consecutive patients with pT1-T4 melanoma undergoing SLNB between 2006 and 2014 was analyzed using the CP-GEP model. CP-GEP combines Breslow thickness and patient age with the expression levels of eight genes from the primary melanoma. Stratification is based on their risk for nodal metastasis: CP-GEP Low Risk or CP-GEP High Risk. ResultsThe SLNB positivity rate was 13%. Of 421 primary melanomas, the CP-GEP model identified 86 patients as having a low risk for nodal metastasis. In patients with pT1-2 melanomas, the SLNB reduction rate was 35.4% (95% CI: 29.4–41.8) with a negative predictive value (NPV) of 96.5% (95% CI: 90.0–99.3). Among patients with pT1-3 melanomas, CP-GEP suggested a SLNB reduction rate of 24.0% (95% CI: 19.7–28.8) and a NPV of 96.5% (95% CI: 90.1–99.3). Only one of 118 pT3 tumors was classified as CP-GEP Low Risk, and all pT4 tumors were classified as being high risk for nodal metastasis. ConclusionThis study demonstrates that CP-GEP can identify patients with a low risk for nodal metastasis. Patients with pT1-2 melanomas have the highest clinical benefit from using the test, where 35% of the patients could forgo a SLNB procedure.

Highlights

Cutaneous melanoma constitutes one of the most common malignancies in fair-skinned populations, where the globalPlease cite this article as: I
Between 2006 and 2014 there were 489 consecutive patients above the age of 18 years that underwent sentinel lymph node biopsy (SLNB) following the diagnostic excision of their primary cutaneous melanoma
Out of the 489 patients, 425 patients were eligible for inclusion and had tumor material sent for RNA extraction and Quantitative polymerase chain reaction (qPCR)

Summary

Introduction

Cutaneous melanoma constitutes one of the most common malignancies in fair-skinned populations, where the global. The SLNB technique was introduced by Morton et al, in 1992 [6] as a surgical method to identify and stage regional lymph nodes in patients with clinical stage I/II melanoma. A positive sentinel lymph node (SLN) has become the most important determinant for adjuvant systemic therapy [8e12]. In patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) serves as an important technique to asses disease stage and to guide adjuvant systemic therapy. A model using clinicopathologic and gene expression variables (CP-GEP; Merlin Assay) has recently been introduced to identify patients that may safely forgo SLNB. Of 421 primary melanomas, the CP-GEP model identified 86 patients as having a low risk for nodal metastasis. Conclusion: This study demonstrates that CP-GEP can identify patients with a low risk for nodal metastasis. Patients with pT1-2 melanomas have the highest clinical benefit from using the test, where 35% of the patients could forgo a SLNB procedure

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