A DNA-based blood panel developed by Exact Sciences and the Mayo Clinic accurately detected liver cancer across all stages of the disease and outperformed the most commonly used serum test in a phase 2 clinical validation study.
The assay tracks six methylated DNA markers found in blood plasma to detect hepatocellular carcinoma with 95% overall sensitivity: 75% for stage 0 disease, 93% at stage A, 93% at stage B, 96% at stage C and 100% at stage D.
The panel's ability to avoid false positives was equally high, with 95% specificity in healthy controls and 86% in cirrhotic controls, and was more accurate than clinically ordered tests of serum alpha-fetoprotein levels. The data was unveiled in an oral presentation at the Digestive Disease Week meeting in Washington, D.C., by John Kisiel, M.D., an assistant professor of medicine at the Mayo Clinic.
Under a long-standing research collaboration between Exact Sciences and the Mayo Clinic, researchers used whole-methylome DNA sequencing to identify markers in HCC tissues. The assay was evaluated using frozen plasma samples from an independent archive, including 95 confirmed HCC cases, 51 cirrhotic controls and 98 controls with no liver disease or history of cancer.
Exact Sciences and the Mayo Clinic hope to further optimize the panel and plasma collection conditions prior to a phase 3 study.
Hepatocellular carcinoma is a growing cause of cancer-related death in the U.S., with five-year survival rates of less than 5% in late-stage disease; however that can be improved to 40% to 70% when the disease is screened and treated early.
The current surveillance tests recommended for cirrhotic patients, including ultrasound and measuring AFP levels, are less sensitive to early-stage disease compared to later stages. In addition, AFP results can return positive during pregnancy, as well as for other tumors.
Exact Sciences saw success with its 2014 FDA approval of Cologuard, an at-home, noninvasive screening test for colorectal cancer. Cologuard analyzes stool DNA and blood biomarkers, and can spot 92% of cancers and 69% of the most advanced precancerous polyps in typical patients, according to the company. It was also the first product to receive parallel review and clearance under an FDA/CMS pilot program designed to accelerate reimbursement.
However, the U.S. Preventive Services Task Force would withhold from recommending Cologuard for screening in October 2015, causing reimbursement troubles. The company would later scrap its plans for a lung cancer screening test developed in collaboration with MD Anderson Cancer Center, citing the high costs of proving its value. As of June 2016, the USPSTF recommends Cologuard screening every three years and the test is covered by most insurers and Medicare.
Editor's note: This story was updated with the current USPSTF recommendations for Cologuard.