A novel noninvasive test for colorectal cancer (CRC) screening demonstrated high sensitivity for detecting colorectal malignancy.
The test measures different kinds of DNA changes, known as methylation and mutation, along with a measure of fecal blood and by combining these measures, doctors can be shown the kinds of biological changes that are most frequently found in precancers and cancers in the colon.
Scientists at the Exact Sciences Corporation (Madison, WI, USA) working with those at the Mayo Clinic, (Rochester, MN, USA) analyzed 1,003 patient samples from 36 study sites. They developed an analytic algorithm for the novel, automated stool DNA-based test platform, which generated a positive or negative result for each patient. The specimens were collected either before colonoscopy bowel preparation in screening and surveillance patients or at least seven days postcolonoscopy from patients with colorectal cancer and large precancerous growths.
The control group included 796 patients with negative colonoscopies or small polyps of less than 1 cm, and the case group included 207 patients with confirmed CRC or precancers. The team was able to demonstrate that CRC and advanced precancers can be detected noninvasively by a manual multitarget stool DNA-based test (sDNA-MT) comprising exfoliated DNA markers plus β-actin and fecal hemoglobin. The clinical performance of the sDNA-MT test, using an optimized automated analytic platform and logistic algorithm could facilitate the routine performance of sDNA-MT for CRC screening by molecular diagnostics capable clinical laboratories.
Automated methylation, mutation and actin assays were performed with a Hamilton STARlet fluid handler (Hamilton Robotics; Reno, NV, USA), and Quantitative Allele-specific Real-time Target and Signal amplification (QuARTS) run on an ABI 7500 FastDx real time thermal cycler (Applied Biosystems; Foster City, CA, USA). The test detected 98% of all cancers as well as 83% of precursors with high-grade dysplasia, and 57% of precursors 1 cm or larger overall, at 90% nominal specificity. CRC patients were typically referred to colonoscopy for symptoms and test sensitivity may be elevated relative to that seen with screening.
Graham P. Lidgard, PhD, the chief science officer at Exact Sciences, said, "We are encouraged by the results of this study for detecting cancer and cancer precursors, especially the precursor lesions with high-grade dysplasia, an abnormality broadly recognized as being associated with a higher risk for progression to cancer itself. Current screening tests using only fecal occult blood are biologically limited in their ability to detect precursors to colorectal cancer." The study was presented at the 11th Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research, held October 16-19, 2012, in Anaheim (CA, USA).