Impact of Gene Expression Profile Testing on the Management of Squamous Cell Carcinoma by Dermatologists

October 2019 | Volume 18 | Issue 10 | Original Article | 980 | Copyright © October 2019

Rebeca Teplitz BA,ª Giselle Prado MD,B Graham H. Litchman DO MS,B Darrell S. Rigel MD MSc

ªMedical Student, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY

BClinical Research Fellow, National Society for Cutaneous Medicine, New York, NY

cClinical Professor, Department of Dermatology, NYU School of Medicine, New York, NY

Abstract
Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing likely due to improved detection and a growing elderly population. Although the prognosis of cSCC is excellent with complete surgical excision, many patients who go on to develop metastasis are initially classified as low-risk. The most commonly used staging systems, American Joint Committee on Cancer (AJCC) and Brigham Women's Hospital (BWH), have low sensitivity and low positive predictive value for predicting metastasis. A gene expression profile test (cSCC-GEP) is in development to identify patients with cSCC at high risk for metastasis and death.

Objective: To determine the impact of cSCC-GEP test results on management decisions made by dermatologists for cSCC patients. Design, Setting, and Participants: 402 dermatologists attending a national dermatology conference completed an online survey designed to determine the impact of cSCC-GEP test results on management decisions in a variety of clinical situations. Participants answered a series of questions related to three cSCC patient vignettes, each featuring different patient and lesion characteristics.

Main Outcomes and Measures: Proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, or sentinel lymph node biopsy (SLNBx) for each patient vignette (without cSCC-GEP results, with a lower risk result, or with a higher risk result). The effect of the test results on the follow-up intervals recommended by dermatologists was also examined. Results: In the majority of vignettes, a lower risk cSCC-GEP test result led to a statistically significant decrease in the proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up. Conversely, a higher risk cSCC-GEP result significantly altered management toward increased intensity (more recommendations for radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up) in all vignettes.

Conclusions and Relevance: The results of a cSCC-GEP test appear to significantly impact decisions made by dermatologists regarding subsequent management, SLNBx, and follow-up intervals for patients with cSCC.

J Drugs Dermatol. 2019;18(10):980-984.

BACKGROUND

Nonmelanoma skin cancer (NMSC) is the most common malignancy in the United States. It is estimated that cutaneous squamous cell carcinoma (cSCC) represents 20% of NMSC cases with an approximate annual incidence of over 700,000, which is increasing yearly.1,2 While the exact incidence of cSCC is not included in national cancer registries, a recent study showed an increase of 263% in the incidence of cSCC between 2000-2010 compared to 1976-1984.3 This increasing incidence is likely due to both improved detection and the growing elderly population.4 Although the prognosis of cSCC is generally excellent with complete surgical excision, a recent study showed that roughly 4% of cases develop nodal metastases and 1.5% die from this disease.2

To more accurately identify cSCC’s at high risk for metastasis or death, there are two main staging systems, American Joint Committee on Cancer (AJCC) and Brigham Women's Hospital (BWH). However these staging systems have low sensitivity (23-46%) and low positive predictive value (12-13%).5-8 Many patients who develop metastasis are initially classified as low-risk, and conversely, some patients who are classified as high-risk do not go on to develop metastatic disease. Thus, accurate identification of high risk cSCC patients is critical. Additionally, the definitive work-up and treatment indicated for high-risk cSCC remains unknown.9 Given the recent FDA-approval of Cemiplimab10 for the treatment of advanced cSCC and its significant side effect profile, it is particularly important that the appropriate patients are selected for this therapy.

A gene expression profile (GEP) test is currently under development (Castle Biosciences Inc., Friendswood, TX). The goal of the 40-gene test is to improve upon current staging systems and identify patients with cSCC at high risk for metastasis and death. Previous analyses have identified 73 genes as associated with cSCC recurrence and metastasis.8 A recent study performed microarray analysis of 80 cSCC lesions to further identify novel genes differentially expressed in high-risk cSCC’s.11 Based on the patient’s expression of these genes, machine learning can