San Francisco, CA—The “eradication” of colorectal cancer (CRC) may be a step closer, based on promising data for stool DNA testing, said David A. Ahlquist, MD, Mayo Clinic, Rochester, MN, at the 2012 Gastrointestinal Cancers Symposium.
Suggesting that his claim is “not too bold, and not hyperbole,” Dr Ahlquist explained that stool DNA testing using next-generation technology is:
Broad application of stool DNA testing in longitudinal screening programs has the potential to effectively prevent CRC by cumulatively high precancer detection, he claimed.
The noninvasive DNA test, currently in development, involves no diet or medication restrictions and no bowel preparation, and it is performed at home using a stool sample. It works by detecting tumor-specific DNA alterations in cells that are shed into the stool from precancerous and cancerous lesions.
Richard M. Goldberg, MD, Ohio State University Medical Center, chair of the meeting’s steering committee, commented, “The data are very impressive. I’m surprised and delighted at how good it is.” He said that if the DNA stool test could substitute for screening colonoscopy, the cost-savings would be substantial. “This is potentially a very exciting development,” he said.
“I would like to see it cost less than $300. And this will be just the tip of the submerged iceberg. The reduction in false-positives and the effect of cancer prevention are all downstream cost burdens that are enormous,” Dr Ahlquist said.
A multicenter case-control study of 678 patients, including 253 with CRC and 130 with advanced adenomas, detected 85% of nonmetastatic CRCs and 64% of adenomas (in pooled analysis of the training and validation sets; Ahlquist D, et al. Gastroenterology. 2012;142:248-256). “When you apply the 64% sensitivity rate for precancerous lesions, repeated over time, by the third time you have an aggregate 95% sensitivity,” Dr Ahlquist said.
Detection increased with adenoma size: 64% for adenomas >1 cm, 77% for those >2 cm, and 90% for those >3 cm; fewer than one third of adenomas <1 cm were picked up. “This is most important,” he said. “As a polyp grows, the risk of transformation to cancer increases, and the sensitivity of this test increases in proportion.”
Lesions were detected in the proximal and distal colons with equal accuracy: 87% and 83%, respectively, for cancerous lesions and 55% and 53% for adenomas.
Dr Ahlquist mentioned that the emerging plasma-based tests, one of which, plasma Septin 9, is commercially available, have not been shown to reliably detect adenomas. Using paired samples from the same patients in a direct comparison of stool DNA testing with the Septin 9 plasma test, he and his colleagues found that 82% of large adenomas were detected by stool DNA testing compared with just 14% by the plasma test, with false-positive rates of 7% and 23%, respectively. For CRC, the stool DNA test detected 87% compared with 60% by the plasma test.
Final validation of the test’s accuracy is under way in a multicenter study, the results of which should support US Food and Drug Administration approval, he said.—CH
