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Gastrointestinal Cancers Symposium

Blood-Based Assay Sparks Hope for Improving Early Detection and Prevention of Colorectal Cancer

Dr. Shai Friedland

A blood test for early detection of colorectal adenomas and cancer shows promise for improving survival and prevention of colorectal cancer (CRC) by enabling the stratification of patients for screening or post-polypectomy surveillance colonoscopy, according to a new study (Abstract 50).

The lack of adherence to guidelines for screening and follow-up post-polypectomy is attributed to 50,000 deaths annually from colorectal cancer. The natural history and shared etiology of adenomas and CRC inform integration of clinically relevant biomarkers.

The lack of adherence to guidelines for screening and follow-up post-polypectomy is attributed to 50,000 deaths annually from colorectal cancer.

Adenomas account for 98% of actionable colonoscopies, while stool tests have low sensitivity for advanced adenomas (AA, 24%-42%). The two objectives of early screening and surveillance are early detection to improve survival and prevention of CRC through removal of adenomas using colonoscopy.

The study, led by Shai Friedland, MD, of Stanford University, was featured in a Poster Session during the 2021 Gastrointestinal Cancers Symposium.

The prospective, blinded study was conducted at the VA Palo Alto Health Care System and included 458 participants who had no prior diagnosis of CRC. Blood was drawn prior to colonoscopy, and the cohort included both screening (239) and surveillance (219) patients.

The noninvasive multimodal FirstSight blood test analyzed two biomarkers, including gastrointestinal epithelial cells and somatic mutations of cell-free DNA. The probability of advanced neoplasia was obtained by ordinal/nominal logistic regression methods together with SEER-incidence rate and prior history of AAs on a training set of 346 patients. The cutpoint for the quantitative score was fixed and the remaining 112 participants were tested.

Balanced distribution of about three-fourths of patients in each disease category were randomly selected for training and algorithm development, while the remaining quarter of participants were used for validation. Eighty-six percent of the participants who indicated for colonoscopy were asymptomatic, and 14% had symptoms or a positive fecal test.

The blood test showed high sensitivity for AAs and CRC combined while retaining high specificity. A cutpoint was selected to obtain a test specificity (non-neoplastic finding or negative colonoscopy) of 90%, resulting in a sensitivity of 100% and 80% for detection of CRC and advanced neoplasia (AN = CRC+AA), respectively, on the training patients. The area under the ROC curve is 0.91. Validation using the fixed cutpoint and 112 test subjects achieved 91.4% specificity and 100% and 75% sensitivity for CRC and AN, respectively.

Investigators concluded that the FirstSight blood test is developed for the early detection of CRC neoplasia given its high sensitivity for CRC advanced neoplasia, while retaining high specificity. The quantitative nature of the score has the potential to enable prognostic stratification of patients for screening or post-polypectomy surveillance colonoscopy.

Discussant Jason A. Zell, DO, MPH, of the Chao Family Comprehensive Cancer Center at UC Irvine Health, said the study’s data look encouraging. “I do see a role for this type of test, also in the setting of tertiary prevention for colorectal cancer survivors,” he said. “It’s very exciting research; I look forward to more research in each of these domains (primary, secondary and tertiary prevention).”

— Geraldine Carroll

ASCO Career Center