Gene expression profile (GEP) testing has been shown, in combination with established clinical and histologic factors, to refine risk prediction for outcomes of interest for multiple diseases.1 The recently developed and validated 40-GEP test for CSCC is the first clinically available GEP test used to predict the risk of nodal and distant metastasis and should only be considered for use in tumors with one or more high-risk factors.2 The probability of nodal or distant CSCC metastasis varies based on established clinicopathologic risk factors, which current management algorithms use to provide recommendations appropriate for each individual patient. GEP testing for CSCC has the ability to provide clinicians with objective data from the primary tumor that can augment existing risk stratification, which could be an important and beneficial advance in patient care.
CSCC patients who ultimately experience poor outcomes have a variety of initial presentations and start their clinical journeys in diverse practice settings across the country. The clinician performing the initial biopsy may not be responsible for managing the advanced sequelae of that same lesion years after its diagnosis and primary treatment, and their initial assessment of patient risk may or may not be accurate. This article illustrates how collective decision making can help bridge existing gaps in current clinical guidelines to develop a plan of care for high-risk patients whose level of risk is unknown. The information gained from GEP testing provides more precise risk stratification and allows patients at highest risk of poor outcomes to be managed more aggressively and followed more closely. Because of the wide variety of risk-assessment approaches, treatment settings, and specialties involved in treating CSCC, it is unlikely that there will be a standardized approach to initiating GEP testing, but rather that a nuanced assessment of each patient’s individual risk profile will be required to arrive at a decision. Furthermore, as the authors emphasize, GEP test results should be interpreted in the context of each patient’s individual clinicopathologic risk factors to assess the appropriateness of nodal evaluation, the need for adjuvant radiation therapy, the frequency of follow-up intervals, and the level of required surveillance.
1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121.
2. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021;84(2):361-369.