In Colorectal Cancer Screening, Multitarget Stool DNA Test Appears to Have Higher Sensitivity Than Fecal Immunochemical Test

EBM Focus - Volume 9, Issue 13

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Reference: N Engl J Med 2014 Mar 19 early online (level 2 [mid-level] evidence)

Colorectal cancer is a major cause of morbidity and mortality in the United States (CA Cancer J Clin 2013 Jan;63(1):11). The American Cancer Society and American Gastroenterological Association recommend screening for colorectal cancer beginning at age 50 years, and list both stool DNA test and fecal immunochemical test as options for detecting cancer (CA Cancer J Clin 2008 May-Jun;58(3):130 full-text). The diagnostic performance of a new stool DNA test was compared to the fecal immunochemical test for detection of colorectal cancer in a recent cohort study of 11,016 asymptomatic persons aged 50-84 years with average risk for colorectal cancer.

All patients had the multitarget DNA test and fecal immunochemical test done from a single stool sample prior to planned routine screening colonoscopy (reference standard). The DNA test consisted of a hemoglobin immunoassay plus quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin. Patients with a personal or family history of colorectal cancer or a personal history of colorectal neoplasia, digestive cancer, or inflammatory bowel disease were excluded. A total of 9,989 patients (91%) were analyzed after exclusion of 1,027 with uninterpretable or missing results for any screening test, including problems with collection of the stool sample for the DNA test and technical failure due to insufficient DNA. The cutoffs for a positive result were defined as ≥ 183 on the composite score from a logistic-regression algorithm for the DNA test, and > 100 ng/mL hemoglobin for the fecal immunochemical test.

During colonoscopy, 65 persons (0.7%) were found to have colorectal cancer and 757 persons (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps ≥ 1 cm in greatest dimension). For detection of any colorectal cancer, the multitarget stool DNA test had a sensitivity of 92.3% vs. 73.8% with the fecal immunochemical test (p = 0.002). The corresponding number needed to screen to detect 1 case of colorectal cancer was 166 with the multitarget stool DNA test vs. 208 with the fecal immunochemical test. Similarly, for detection of advanced precancerous lesions, the multitarget stool DNA test had a sensitivity of 42.4% vs. 23.8% with the fecal immunochemical test (p < 0.001). The number needed to screen to detect 1 advanced precancerous lesions was 31 with the multitarget stool DNA test vs. 55 with the fecal immunochemical test. The specificity for no colorectal cancer or advanced precancerous lesion was 86.6% with the multitarget stool DNA test vs. 94.9% (p < 0.001) with the fecal immunochemical test. For detection of either colorectal cancer or advanced precancerous lesions, the multitarget DNA test had a positive predictive value of 23.6% and negative predictive value of 94.7%, and the fecal immunochemical test had positive predictive value of 32.6% and negative predictive value of 93.6%.

These results show that stool DNA testing is associated with significantly higher sensitivity than fecal immunochemical testing for detection of colorectal cancer and advanced precancerous lesions, at the expense of lower specificity. For a screening test for cancer, the higher sensitivity is more important, as long as there are not too many false positives, which appears to be the case here. Although the DNA testing had a higher detection rate for identifying colorectal cancers compared to the immunochemical testing, the greater ability to detect precancerous lesions is at least as significant, since the optimal goal is to prevent cancer. Further studies are required to determine the optimal interval screening duration for stool DNA testing, and to address other practical aspects of testing, such as stool collection and ensuring samples have sufficient DNA. The cost of DNA testing must also be considered, particularly since many individuals who do not currently have routine screening may not have access to this technology. Moreover, randomized trials are needed to determine whether stool DNA testing improves clinical outcomes such as mortality when compared to other screening tests.

For more information see the Colorectal cancer screening topic in DynaMed.

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