Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

Abstract

Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature

Adjuvant therapy for high‐risk cutaneous squamous cell carcinoma: 10‐year review

“…More prospective, randomized, large cohort, clinical trials are needed for collecting high‐quality data from which consensus guidelines can be developed for determining which patients might benefit most from a specific type of adjuvant therapy or combination of therapies. Importantly, this includes prospective studies of prognostic testing, such as GEP testing or SLNB, in patients with high‐risk cSCC 2,23–27 . This additional testing would help determine which patients truly need adjuvant therapy and which patients may be managed more appropriately without adjuvant therapy.…”

“…7 , 8 Given the high and growing incidence of cSCC, 7 , 8 , 16 , 17 , 18 the percentage of patients with cSCC who develop recurrence and/or metastasis corresponds to a substantial number of individuals who would benefit from more accurate prognosis for better‐informed decision‐making regarding follow‐up and adjuvant treatment. 5 , 7 , 17 , 19 , 20 , 21 , 22 These high‐risk patients may require more intensified management plans, 2 , 23 , 24 , 25 , 26 , 27 which often include adjuvant radiation therapy (ART) and/or systemic therapy (e.g., chemotherapy, immunotherapy, and/or targeted therapy). Thus, there is an unmet clinical need for improved prognostication to guide decision making by physicians and their patients with high‐risk cSCC regarding adjuvant therapy and/or clinical trials involving these adjuvant treatment modalities.…”

“…7 , 23 Tumor‐specific prognostic tools, such as molecular biomarker assays and gene expression profiling, have shown utility for guiding decisions on patient management in various types of cancer. 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 A recently validated, clinically available, 40‐gene expression profile (40‐GEP) test that identifies patients with cSCC at low, moderate, and high risk for developing metastasis 26 has clinical application for guiding management intensity decisions. 23 This test could potentially be used to determine which patients would most likely benefit from adjuvant therapy and warrants further investigation in this setting.…”

Overview of genetic signaling pathway interactions within cutaneous malignancies

“…This test will help determine metastasis risk among high risk cSCC patients. Thus, the GEP test, when available, should help improve prognosis projections for thus tumors labelled as poor prognosis cSCC [96] .…”

Gene Expression Profile Testing in Skin Cancer Prognosis: The Data is Clear – It’s Time to Get On Board

“…A 40-GEP test has shown early promise for assessing prognosis in patients with advanced cutaneous squamous cell carcinoma. 16 There have now been over 20 independent peer-reviewed data-driven studies demonstrating consistent clinical validity, efficacy, and positive impact of the 31-GEP test. Given this strong existing supportive published evidence, discounting the value of GEP testing based on hypothetical models, inter-specialty competition with concerns regarding personal adverse economics or personal biases/conflicts for those that may be developing competitive methodologies leading to the subjective/hypothetical defining of "harm" for patients is not data justified.…”