Abstract

Introduction: The histologic identification of poor differentiation is a well-documented risk factor for metastasis in cutaneous squamous cell carcinoma (cSCC) and a high-risk factor for Brigham and Women’s Hospital T-stage (BWH). However, as previously reported (Prezzano etal.2021), differentiation is an imperfect risk indicator due to ~30% guesswork and subjectivity in distinguishing between moderate and poor classifications. An objective prognostic biomarkers, the 40-GEP test was independently validated to accurately classify risk for regional or distant metastasis into three categories: low (Class 1), moderate (Class 2A), or high risk (Class 2B). Objective: The goal of this study was to investigate if 40-GEP stratifies risk among a potentially histologically ambiguous cohort to support risk-aligned treatment decisions. Methods: From a previously published multi-center, independent validation cohort (Ibrahim et al. 2021) (n=420), a subset of cases was identified whose BWH T-stage would change if the tumor differentiation status of ‘moderate’ or ‘poor’ was downgraded or upgraded, respectively. These cases were imputed to the opposite result and then re-staged (n=171). Kaplan Meier survival analysis was performed. Results: Potential uncertainty in histological differentiation resulted in 132 and 39 patients up- and down-staged respectively. Within this subset, the overall 3-year metastasis-free survival was 81.9%. Importantly, the 40-GEP was able to significantly stratify risk (p=0.02; 90.1%Class 1, 78.6% Class2A, 62.5% Class2B). Conclusion: The 40-GEP can aid staging and risk assessment in situations in which the distinction between poor and moderate histological grading is challenging, thus adding clarity and confidence to risk-aligned treatment decisions for the benefit of patients.

Financial Disclosure:

Speaker	Ineligible Company	Affiliation/Relationship	Ongoing/Ended	Role
Sherrif F. Ibrahim, MD, PhD	Castle Biosciences, Inc.	Speaker	Ongoing	Oral Abstact Presenter