On October 28, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the presentation of a development update and validation data for its cutaneous squamous cell carcinoma (SCC) prognostic test, DecisionDx-SCC (Press release, Castle Biosciences, OCT 28, 2019, View Source [SID1234549951]).

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The study titled, "Development and validation of a prognostic gene expression profile (GEP) for stratification of cutaneous squamous cell carcinoma (SCC) patients by 3-year risk of regional or distant metastases," was presented during an Oral Abstract session at the American Society for Dermatologic Surgery (ASDS) Annual Meeting, October 24-27 in Chicago.

Study Background

Approximately 1 million patients are diagnosed with SCC in the U.S. each year, and the incidence continues to grow.
Many patients with SCC will have a favorable prognosis, but an estimated 15,000 people in the U.S. die from SCC each year, surpassing the number of U.S. deaths from cutaneous melanoma estimated to be as high as 9,000.
National guidelines define different treatment pathways and follow-up schedules for low-risk and high-risk SCC patients, but the low positive predictive value (PPV) of available staging systems means that the majority of high-risk patients do not develop metastases. Thus, many high-risk patients may be over-treated with radiation, chemotherapy or other interventions even when they may not be needed.
There is a clear need for more accurate methods to identify high-risk SCC patients to appropriately direct work-up and treatment plans.
To address this need, Castle Biosciences has developed DecisionDx-SCC, a proprietary 40-gene prognostic test. The test was designed to improve upon existing clinicopathologic staging systems and identify SCC patients who are classified as high risk based upon clinicopathologic staging, but who are actually at a low biological risk for metastasis, and thus, can be considered for de-escalation in their treatment plan. Conversely, the test is also designed to identify a biologically high-risk group that has a significantly higher risk of metastasis than would be determined by clinicopathologic staging alone.

Study Findings

Successful development of a 40-gene signature that identifies three groups of patients with significantly different risk for regional/distant metastasis using a training set of 122 patients.
The multicenter validation study included 321 patients, of which 93% had one or more high-risk features and 52 patients experienced metastasis.
Patients with a 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 Class 1 was 91.1%. Among all patients in the study, 63% had a Class 1 (lowest risk) result. This group could be considered for de-escalation in their treatment plan.
The PPV for DecisionDx-SCC Class 2B was 60% compared to the PPV for Brigham and Women’s Hospital (BWH) staging of 35.3% and American Joint Committee on Cancer (AJCC version 8) staging of 20.9%.
DecisionDx-SCC demonstrated strong independent prognostic value in multivariate analyses compared to the BWH and AJCC v8 staging systems. Specifically, when compared to the BWH staging system, DecisionDx-SCC Class 2B had a hazard ratio (HR) of 8.9 (p<0.001) compared to an HR of 1.9 for BWH high risk (p<0.05). Similarly, when compared to the AJCC v8 staging system, DecisionDx-SCC Class 2B had an HR of 9.8 (p<0.001) compared to an HR of 2.6 for AJCC high risk (p<0.001).
"Clinical validation of this prognostic test for SCC demonstrates significant progress towards improved identification of high-risk patients beyond currently available staging systems," commented Ashley Wysong, M.D., University of Nebraska Medical Center, Omaha NE, study investigator and presenter. "Clinical application of this test may allow us to de-escalate care in patients identified as low risk by tumor biology, as well as provide us objective data to guide implementation of adjuvant radiation, chemotherapy and clinical trial recommendations for those at actual high risk."

Additional DecisionDx-SCC performance studies are currently underway, including a prospective study. The DecisionDx-SCC test is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC), a nonmelanoma skin cancer, is one of the most common cancers. Approximately 1,000,000 patients are diagnosed with SCC each year in the U.S. Most patients have a favorable prognosis, but a subset of patients will develop metastasis and up to 15,000 patients each year die from their disease, exceeding the number of deaths from cutaneous melanoma. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients who develop metastatic disease are misidentified as low risk. This may lead to over and undertreatment of a substantial number of 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 SCC at high risk for metastasis or recurrence, in order to enable more informed clinical decisions regarding adjuvant therapy and other management options.