Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

Abstract

PURPOSE More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis. PATIENTS AND METHODS Genes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables. RESULTS Expression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%). CONCLUSION A combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

“…At the same time, most will recognize the fact that classic staging with histopathological and clinical factors will become obsolete once high-level molecular biomarkers are able to reliably predict prognosis. For instance, there are already a few panels of gene expression profiles (GEP) being tested for this purpose [29][30][31].…”

Deselecting Melanoma Patients for Sentinel Lymph Node Biopsy During COVID-19: Clinical Utility of Tumor Molecular Profiling

“…This is shown by a representative case of a Mayo Clinic patient who enrolled in a feasibility study of a molecular method aimed to identify melanoma patients who are so low risk for metastasis that they can safely forgo SLN biopsy (Figure). 3 This study was reviewed and approved by the Mayo Clinic Institutional Review Board. Following diagnosis, the patient met with a surgeon, underwent preoperative evaluation with customized testing to ensure a safe recovery, and completed a technetium-99m scintigraphy (single-photon emission computerized tomography [SPECT]) in nuclear medicine combined with computed tomography (CT) to produce SPECT-CT scans.…”

“…Nodal metastasis is found in less than 20% of patients who undergo SLN biopsy. 3 Although the removal of negative SLN has no discernible therapeutic effect, all patients who undergo SLN biopsy encounter a greater than 10% risk of complications. 4 There is a need for methods to identify patients who are so low risk that they can safely forgo SLN biopsy.…”

“…We have previously reported on a melanoma risk-stratification approach which combines clincopathologic (CP) variables with a gene expression profile (GEP) from primary diagnostic biopsy tissue. 3 Using the CP-GEP test, up to 80% of patients with T1b, 48% of patients with T2a, and 24% of patients with T2b melanoma may forgo the SLN biopsy procedure as they are categorized as low risk for nodal metastasis with an error rate of less than 5%. 3,5 Test results are available within days (Figure) and do not require the patient to interact with health care providers.…”

“…3 Using the CP-GEP test, up to 80% of patients with T1b, 48% of patients with T2a, and 24% of patients with T2b melanoma may forgo the SLN biopsy procedure as they are categorized as low risk for nodal metastasis with an error rate of less than 5%. 3,5 Test results are available within days (Figure) and do not require the patient to interact with health care providers. Hospital resources can be prioritized to other tasks.…”