Breslow thickness 2.0: Why gene expression profiling is a step toward better patient selection for sentinel lymph node biopsies

Risk-stratification of cutaneous melanoma is important. Patients want to know what to expect after diagnosis, and physicians need to decide on a treatment plan. Historically, melanoma that had spread beyond the skin and regional lymph nodes was largely incurable, and the only approach to preventing a bad outcome was surgery. Through the seminal work of Alexander Breslow and Donald Morton, a system was devised to carefully escalate surgery based on primary tumor thickness and sentinel lymph node status. Today, we know that prophylactic lymph node dissections do not improve survival, but we continue to appreciate the prognostic implications of a positive sentinel node and the benefits of removing nodal metastases, which facilitates locoregional disease control. However, the question arises whether we can better select patients for sentinel lymph node biopsies (SLNB) as, currently, 85% of these procedures are negative and non-therapeutic. Here, we argue that gene expression profiling (GEP) of the diagnostic biopsy is a valuable step toward better patient selection when combined with reliable clinicopathologic (CP) information such as patient age and Breslow thickness. Recently, a CP-GEP-based classifier of nodal metastasis risk, the Merlin Assay, has become commercially available. While CP-GEP is still being validated in prospective studies, preliminary data suggest that it is an independent predictor of nodal metastasis, outperforming clinicopathological variables. The hunt is on for Breslow thickness 2.0.