Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma Eligible for Lymph Node Sentinel Biopsy (CORRESPOND): an Observational Prospective Study.

Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations [1].

For patients with clinically node-negative (cN0) disease, sentinel lymph node biopsy (SLNB) is indicated for all patients with a melanoma of thickness of 0.8 mm or more (>pT1b) to stratify the prognosis and guarantee access to systemic adjuvant treatments [1].

Indeed, adjuvant immune checkpoint inhibitors or anti-BRAF/MEK targeted agents were first demonstrated to improve clinical outcomes in patients with nodal involvement (stage III melanoma). Subsequently, immune-checkpoint inhibitors demonstrated a benefit in terms of disease-free survival also in patients with stage IIB and IIC melanoma, i.e., with melanoma of thickness of 2 mm or more (>pT3b). As a consequence, in this subgroup of patients, SLNB has lost its therapeutical implications and maintains only a role for prognostication, i.e., in the distinction between stages IIB-IIC (SLNB-negative; 71% of cases) and stage III (SLNB-positive; 29% of cases) [1].

However, SLNB can be complicated by seroma, bleeding, wound infection, nerve damage, and even low rates of lymph edema have been reported. Moreover, depending on the country and healthcare system, it is a costly procedure for patients and society. According to an idea of professor Umberto Veronesi, Gentilini et al. demonstrated that the omission of SLNB in patients with cT1N0M0 breast cancer has not an impact on distant disease-free survival at 5 years (SOUND trial) [2]. Novel prognostic biomarkers for melanoma can substitute the SLNB role in prognostication and eventually lead to SLNB de-escalation.

Gene expression profiles (GEPs) and circulating tumor DNA (ctDNA) represents promising methods to assess tumor burden and tumor invasiveness, thus stratifying the prognosis [1].