Independent Dutch Validation Study of CP-GEP (Merlin Assay) for the Prediction of Nodal Metastasis and Long-Term Outcome in Patients with Primary Cutaneous Melanoma.

BACKGROUND

Currently, sentinel lymph node biopsy (SLNB) is considered standard staging for patients with stage IB-II melanomas. Owing to recent systemic therapy advances, SLNB is once again being scrutinized. The aim of the current study was to validate the diagnostic accuracy of the clinicopathological gene expression profile (CP-GEP) for risk of sentinel node metastases and recurrence.

PATIENTS AND

METHODS

Samples and clinical data of 252 patients with newly diagnosed clinical stage I/II melanoma between 2007 and 2015 were obtained. CP-GEP included eight target genes associated with tumor development (i.e., MLANA, GDF15, CXCL8, LOXL4, TGFBR1, ITGB3, PLAT, and SERPINE2) and two housekeeping genes in combination with clinicopathological variables, age, and Breslow thickness.

RESULTS

The median age was 57 years old, and 51.4% were female. The median Breslow thickness was 1.8 mm, and 53 patients (21.8%) had a positive SLNB. The median follow-up was 91 months. CP-GEP identified 68 (28%) patients as CP-GEP low risk and 175 (72%) as high risk. The sensitivity of CP-GEP was 92.5%, specificity was 33.7%, positive predictive value (PPV) was 28.0%, and negative predictive value (NPV) was 94.1% for all (T1-T4). The CP-GEP had the best performance in T1, with an NPV of 95.2% and an SLNB reduction rate (RR) of 80.8%. In the pT1b-pT2a melanomas with an NPV of 93.3% and a SLNB RR of 45.5% in terms of long-term survival, the 5-year recurrence-free survival (RFS) of CP-GEP low risk was 89.6% versus 76.8% for CP-GEP high-risk patients.

CONCLUSIONS

CP-GEP demonstrated good prognostic performance, particularly for patients with pT1b-pT2a melanoma and thus could be considered a noninvasive alternative for a SLNB.