AACR: Multi-Target Stool DNA Test Detects 98% of Colorectal Cancer
These findings “could lead to noninvasive CRC screening performance with wide accessibility to patients,” said Graham P. Lidgard, PhD, of Exact Sciences Corp., Madison, WI, which developed the test and sponsored the study.
The test comprises three exfoliated DNA markers, methylated BMP3 and NDRG4 and mutant KRAS (7 mutations, codons 12, 13), plus β-actin as well as fecal hemoglobin. This study examined the clinical performance of the sDNA-MT test using an optimized automated analytic platform and logistic algorithm. Stool samples were collected from 1,003 subjects at 36 study sites. Case included 207 patients with confirmed colorectal cancer or precancers and controls were 796 patients with negative colonoscopies or small polyps.
Samples were provided prior to colonoscopy bowel preparation from those presenting for average risk screening for colorectal cancer. Among those with CRC, advanced adenoma or sessile serrate adenoma ≥1 cm, stool was collected at least 7 days post-colonoscopy and prior to surgery or chemoradiation. After performing automated methylation, mutation, and actin assays on the stool samples, the algorithm provided a “positive” or “negative” result based on a predetermined threshold.
“The algorithm provided good discriminative ability, stability, sensitivity and specificity,” Dr. Lidgard noted. At a 90% nominal specificity, sDNA-MT sensitivity for CRC was 98% (91 of 93 patients); for those with stage I, it was 95% (20/21); stage II, 100% (23/23); stage III 96% (26/27); and stage IV, 100% (7/7); stages I-III combined was 97% (69/71).
Patients with CRC “were typically referred to colonoscopy for symptoms and test sensitivity may be elevated relative to that seen with screening,” he noted. The assay was also had 57% sensitivity (65 of 114 patients) for precursors ≥1 cm; for precursors with high grade dysplasia, sensitivity was 86% (12/14).
A phase 3 pivotal clinical trial (the DeeP-C study) is currently ongoing to validate these results.