metastasis can also differ depending on the study population, patient demographics, and practice setting. In addition, the predictive accuracy of staging systems in CSCC can vary; for instance, the positive predictive values for nodal metastasis using the American Joint Committee on Cancer (AJCC) Cancer Staging Manual and Brigham and Women’s Hospital (BWH) staging system range from 14–17% and 24–38%, respectively.4-7 These complexities make it difficult to know which treatment to select at which decision point for patients with high-risk CSCC.
Gene expression profile (GEP) testing can provide information about the biological characteristics of an individual patient’s tumor beyond standard clinicopathologic risk factors. GEP tests have been used successfully in the clinical management of other cancer types (eg, breast, prostate, and melanoma) to identify tumors with high-risk characteristics and help guide prognosis and treatment options.8-11 Recently, a prognostic GEP assay (the 40-GEP test) was developed for predicting the risk of metastasis in localized high-risk CSCC.12 While it is premature to make definitive recommendations about CSCC management based on GEP test results, GEP testing has been validated to predict metastasis. By providing a clearer picture of a tumor’s metastatic risk potential, the 40-GEP test result has the ability to inform risk-appropriate management decisions within established guidelines. GEP test results can be used to identify patients with biologically low-risk tumors who could be considered for de-escalation of treatment and surveillance. Conversely, GEP test results can also be used to identify patients with biologically high-risk tumors who may benefit from more intense treatment options.
One complexity associated with GEP testing for CSCC is identifying the optimal time frame for testing in order to have the greatest impact on treatment decisions. In addition, each specialist has a particular role in CSCC treatment with unique knowledge gaps and would prefer to have GEP test results prior to management decision points. For example, in surgical management decisions, the primary diagnosing provider would benefit from testing prior to referral to the surgeon while the surgeon would need to test prior to planning work-up and definitive management. For decisions on nodal evaluation and adjuvant therapy, GEP testing may help the primary diagnosing provider identify patients who may benefit from referral to the radiation/medical oncologist, while the radiation/medical oncologist may test as part of the treatment decision process. To maximize the utility of the GEP test, the test result needs to be available to the provider at the time in the patient's management plan when clinical decisions are being made. For this reason, it is recommended that GEP testing be pursued at the earliest point in high-risk CSCC management where the results will influence clinical decision making.
The purpose of this article is to provide an early framework for healthcare providers looking to integrate a GEP assay for CSCC into their clinical practice. Based on current risk data, it summarizes the clinical considerations identified by an expert panel reviewing the use of the 40-GEP test in the context of clinical management of high-risk CSCC.
Gene expression profile (GEP) testing can provide information about the biological characteristics of an individual patient’s tumor beyond standard clinicopathologic risk factors. GEP tests have been used successfully in the clinical management of other cancer types (eg, breast, prostate, and melanoma) to identify tumors with high-risk characteristics and help guide prognosis and treatment options.8-11 Recently, a prognostic GEP assay (the 40-GEP test) was developed for predicting the risk of metastasis in localized high-risk CSCC.12 While it is premature to make definitive recommendations about CSCC management based on GEP test results, GEP testing has been validated to predict metastasis. By providing a clearer picture of a tumor’s metastatic risk potential, the 40-GEP test result has the ability to inform risk-appropriate management decisions within established guidelines. GEP test results can be used to identify patients with biologically low-risk tumors who could be considered for de-escalation of treatment and surveillance. Conversely, GEP test results can also be used to identify patients with biologically high-risk tumors who may benefit from more intense treatment options.
One complexity associated with GEP testing for CSCC is identifying the optimal time frame for testing in order to have the greatest impact on treatment decisions. In addition, each specialist has a particular role in CSCC treatment with unique knowledge gaps and would prefer to have GEP test results prior to management decision points. For example, in surgical management decisions, the primary diagnosing provider would benefit from testing prior to referral to the surgeon while the surgeon would need to test prior to planning work-up and definitive management. For decisions on nodal evaluation and adjuvant therapy, GEP testing may help the primary diagnosing provider identify patients who may benefit from referral to the radiation/medical oncologist, while the radiation/medical oncologist may test as part of the treatment decision process. To maximize the utility of the GEP test, the test result needs to be available to the provider at the time in the patient's management plan when clinical decisions are being made. For this reason, it is recommended that GEP testing be pursued at the earliest point in high-risk CSCC management where the results will influence clinical decision making.
The purpose of this article is to provide an early framework for healthcare providers looking to integrate a GEP assay for CSCC into their clinical practice. Based on current risk data, it summarizes the clinical considerations identified by an expert panel reviewing the use of the 40-GEP test in the context of clinical management of high-risk CSCC.
METHODS
Panel Review
The panel consisted of Mohs surgeons, surgical oncologists, and a radiation oncologist from academic medical centers and community practices. Information on current clinical practice and considerations for including GEP testing when managing patients with high-risk CSCC was collected via structured oneon- one interviews and panel discussions. The panel reviewed existing clinicopathologic staging and treatment guidelines (eg, American Academy of Dermatology (AAD),13 American College of Radiology (ACR),14 AJCC,15 American Society for Radiation Oncology (ASTRO),16 BWH,6 Mohs Appropriate Use Criteria (AUC),17 and National Comprehensive Cancer Network (NCCN)18), and published expert recommendations and studies (Baum et al,19 Farberg et al,20 Ruiz et al,21 Que et al,22 Skulsky et al,23 and Thompson et al24). The panel then discussed experiences, rationales, and scenarios where information from GEP testing may be helpful for CSCC treatment decisions. Note: The panel referenced Version 2.2020 of the NCCN Guidelines for squamous cell carcinoma; Version 1.2021 was released after the panel discussion.
GEP Assay
Data from the 40-GEP test (DecisionDx-SCC; Castle Biosciences, Inc.) was used as the reference for CSCC GEP testing recommendations; this assay is, currently, the only GEP test commercially available for CSCC healthcare providers.12 The 40-GEP test separates CSCCs by risk of metastasis into low (Class 1), moderate (Class 2A), or high (Class 2B) categories (Figure 1). The assay was developed and validated with samples from patients with one or more high-risk factors (Table 1) and has been shown to have utility in scenarios classified as high-risk by existing guidelines.6,15,17,18 Treatment modality thresholds including test results were synthesized based on overlaps between existing recommendations and 40-GEP data.
The panel consisted of Mohs surgeons, surgical oncologists, and a radiation oncologist from academic medical centers and community practices. Information on current clinical practice and considerations for including GEP testing when managing patients with high-risk CSCC was collected via structured oneon- one interviews and panel discussions. The panel reviewed existing clinicopathologic staging and treatment guidelines (eg, American Academy of Dermatology (AAD),13 American College of Radiology (ACR),14 AJCC,15 American Society for Radiation Oncology (ASTRO),16 BWH,6 Mohs Appropriate Use Criteria (AUC),17 and National Comprehensive Cancer Network (NCCN)18), and published expert recommendations and studies (Baum et al,19 Farberg et al,20 Ruiz et al,21 Que et al,22 Skulsky et al,23 and Thompson et al24). The panel then discussed experiences, rationales, and scenarios where information from GEP testing may be helpful for CSCC treatment decisions. Note: The panel referenced Version 2.2020 of the NCCN Guidelines for squamous cell carcinoma; Version 1.2021 was released after the panel discussion.
GEP Assay
Data from the 40-GEP test (DecisionDx-SCC; Castle Biosciences, Inc.) was used as the reference for CSCC GEP testing recommendations; this assay is, currently, the only GEP test commercially available for CSCC healthcare providers.12 The 40-GEP test separates CSCCs by risk of metastasis into low (Class 1), moderate (Class 2A), or high (Class 2B) categories (Figure 1). The assay was developed and validated with samples from patients with one or more high-risk factors (Table 1) and has been shown to have utility in scenarios classified as high-risk by existing guidelines.6,15,17,18 Treatment modality thresholds including test results were synthesized based on overlaps between existing recommendations and 40-GEP data.
CLINICAL CONSIDERATIONS
For this article, the panel focused on decision-making points
