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
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
