Colon Cancer Screening: A Win for Quality and Technology
Imperiale TF, Ransohoff, DF, Itzkowitz SH, et al
N Engl J Med. 2014;370:1287-1297
Stool-based testing for tumor-specific DNA abnormalities has increased in appeal over the past decade. Preliminary reports suggested a high sensitivity for CRC detection, although a subsequent large-scale screening study showed only a 52% sensitivity for CRC. Refinements in the DNA testing panel have been made, including quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin, plus a hemoglobin immunoassay (fecal immunochemical test [FIT]).
This panel was evaluated in this prospective study of 9989 individuals who were all of average screening risk. FIT values of more than 100 ng of hemoglobin per mL of buffer were considered to be positive. All patients had colonoscopy and, when present, colon polyp resection. The sensitivities of each test for detecting CRC and advanced precancerous lesions are shown in the Table.
Table. Sensitivity of DNA Testing and FIT
Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P < .001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P < .001). The number needed to screen for cancer detection for each of the technologies was 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
This well-done, large validation study provides new evidence of the effectiveness of the revised panel for multitarget stool DNA testing. DNA detected more cancers than FIT; however, DNA testing was also associated with more false-positive results. The cost implications will be important, but I would always welcome a test that gets more patients into colonoscopy.
The implications for follow-up of a positive DNA test and a negative colonoscopy, as well as the intervals for testing, will need to be better clarified. Given the lower specificity and the greater expense of stool DNA testing compared with FIT, it is unlikely that the test would be performed annually as recommended for FIT testing.
The last version of stool-based DNA testing was not acceptable to the US Preventive Services Task Force in their recommendations for CRC screening. An update of those recommendations is currently under way. Hopefully, this new technology will be an acceptable option to patients who decline colonoscopy as the preferred recommended CRC screening test. The ultimate goal is to get more patients screened.
Abstract
Multitarget Stool DNA Testing for Colorectal-Cancer Screening
Imperiale TF, Ransohoff, DF, Itzkowitz SH, et al
N Engl J Med. 2014;370:1287-1297
Study Summary
Stool-based testing for tumor-specific DNA abnormalities has increased in appeal over the past decade. Preliminary reports suggested a high sensitivity for CRC detection, although a subsequent large-scale screening study showed only a 52% sensitivity for CRC. Refinements in the DNA testing panel have been made, including quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin, plus a hemoglobin immunoassay (fecal immunochemical test [FIT]).
This panel was evaluated in this prospective study of 9989 individuals who were all of average screening risk. FIT values of more than 100 ng of hemoglobin per mL of buffer were considered to be positive. All patients had colonoscopy and, when present, colon polyp resection. The sensitivities of each test for detecting CRC and advanced precancerous lesions are shown in the Table.
Table. Sensitivity of DNA Testing and FIT
| Finding | Sensitivity of Detection | ||
|---|---|---|---|
| DNA Testing | FIT | P Value | |
| CRC | 92.3% | 73.8% | .002 |
| Advanced adenoma | 42.4% | 23.8% | < .001 |
| High-grade dysplasia | 69.2% | 46.2% | .004 |
| Serrated sessile polyps ≥ 1 cm | 42.4% | 5.1% | < .001 |
Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P < .001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P < .001). The number needed to screen for cancer detection for each of the technologies was 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
Viewpoint
This well-done, large validation study provides new evidence of the effectiveness of the revised panel for multitarget stool DNA testing. DNA detected more cancers than FIT; however, DNA testing was also associated with more false-positive results. The cost implications will be important, but I would always welcome a test that gets more patients into colonoscopy.
The implications for follow-up of a positive DNA test and a negative colonoscopy, as well as the intervals for testing, will need to be better clarified. Given the lower specificity and the greater expense of stool DNA testing compared with FIT, it is unlikely that the test would be performed annually as recommended for FIT testing.
The last version of stool-based DNA testing was not acceptable to the US Preventive Services Task Force in their recommendations for CRC screening. An update of those recommendations is currently under way. Hopefully, this new technology will be an acceptable option to patients who decline colonoscopy as the preferred recommended CRC screening test. The ultimate goal is to get more patients screened.
Abstract
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