On April 29, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of development and validation data for DecisionDx-SCC, its prognostic test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC) (Press release, Castle Biosciences, APR 29, 2020, View Source [SID1234556780]). The test is expected to be launched commercially in the second half of 2020.
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The article titled, "Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma," was published in the Journal of the American Academy of Dermatology (JAAD).
The study results demonstrate that DecisionDx-SCC is an independent predictor of metastatic risk that can complement current cancer risk-factor staging systems for patients with high-risk SCC.
"As clinicians, we struggle with treatment decisions for patients with high-risk cutaneous squamous cell carcinoma due to the limitations of clinicopathologic based staging systems," said first author, Ashley Wysong, M.D., University of Nebraska Medical Center, Omaha NE. "Validation of the DecisionDx-SCC test demonstrates significant progress in this area by integrating tumor-specific genetic information into clinical decision making. Having better prognostic information helps us to identify patients as low risk by tumor biology and manage them more conservatively with clinical surveillance, as well as provides us with data to help guide implementation of adjuvant interventions and clinical trial recommendations for those identified as high risk."
Disease and Study Background
Approximately 1 million patients are diagnosed with SCC of the skin in the U.S. each year, and the incidence continues to grow; approximately 80% can be cured surgically, but it is estimated that approximately 200,000 patients are diagnosed with high-risk SCC.
SCC National Comprehensive Cancer Network (NCCN) guidelines define treatment pathways based on risk of local recurrence or metastasis. For SCC, there are two clinicopathologically defined categories: low risk and high risk. NCCN defines high risk as SCC patients with one or more of several high-risk clinicopathologic features.
Similar to the Brigham and Women’s Hospital (BWH) and American Joint Committee on Cancer version 8 (AJCCv8) staging systems, risk prediction based on NCCN exhibits low positive predictive value (PPV), meaning that the majority of patients classified as high risk do not develop metastasis.
The study was designed to develop a prognostic test to predict risk of regional or distant metastasis in NCCN-defined high-risk SCC tumors, with the goal of improving risk-directed management.
Study Findings
The 40-gene expression profile test (DecisionDx-SCC) was successfully developed to stratify high-risk SCC patients into three classes based on metastasis risk: Class 1 (low-risk), Class 2A (high-risk), and Class 2B (highest-risk), using a training set of 122 patients.
The independent, multicenter validation study included 321 patients, of which 93% had one or more NCCN-defined high-risk features, and 52 patients experienced metastasis.
DecisionDx-SCC demonstrated strong independent prognostic value in multivariate analyses compared to the BWH and AJCC v8 staging systems. When compared to the BWH staging system, DecisionDx-SCC Class 2B had a hazard ratio (HR) of 8.72 (p<0.0001) compared to an HR of 2.03 for BWH high risk (p<0.05). Similarly, when compared to the AJCC v8 staging system, DecisionDx-SCC Class 2B had an HR of 9.55 (p<0.0001) compared to an HR of 2.68 for AJCC high risk (p<0.001).
Patients with a DecisionDx-SCC Class 1 result (n=203; lowest risk group) had a 91.6% 3-year metastasis-free survival (MFS) rate, significantly better than the MFS rate for patients with a high-risk Class 2A (80.6%; n=93) or highest risk Class 2B (44%; n=25) test result (p<0.0001).
The negative predictive value (NPV) for the DecisionDx-SCC test was 91.1%.
DecisionDx-SCC Class 2B tumors had a PPV of 60%, an improvement upon the PPV observed for both the BWH (35.1%) and AJCC v8 (32.8%) staging systems.
DecisionDx-SCC is the second skin cancer test discovered, developed and validated by Castle Biosciences.
About Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers. Approximately 1 million patients are diagnosed with SCC each year in the U.S. While the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk. National guidelines provide for broad, aggressive treatment plan recommendations relative to low-risk patients. Traditional clinicopathologic based risk-factor staging systems suffer from low positive predictive value; meaning many more patients are classified as high risk than actually develop metastatic disease. This may lead to over- and under-treatment of a substantial number of cutaneous SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with cutaneous SCC at high risk for metastasis or recurrence, in order to enable more informed, objective clinical decisions regarding adjuvant therapy and other management options.