David A. Ahlquist, MD; Daniel J. Sargent, PhD; Charles L. Loprinzi, MD; Theodore R. Levin, MD; Douglas K. Rex, MD; Dennis J. Ahnen, MD; Kandice Knigge, MD; M. Peter Lance, MD; Lawrence J. Burgart, MD; Stanley R. Hamilton, MD; James E. Allison, MD; Michael J. Lawson, MD; Mary E. Devens; Jonathan J. Harrington; Shauna L. Hillman, MS
Acknowledgment: The authors thank EXACT Sciences for performance of all genetic assays on tissue and stools and Beckman Coulter for provision of Hemoccult and HemoccultSensa cards at no cost; Sara Linker Nord for management at coordination center; Kelli Burger for statistical support; Jacalyn McCormick for secretarial support; H. Samuel Wieand, PhD (University of Pittsburgh), for statistical consulting; and Jane Milburn for assistance on protocol development. The authors also thank the physicians and study coordinators at the participating medical centers for their support ( Appendix).
Grant Support: By grants UO1 CA 89389 and UO1 CA 37404 from the National Institutes of Health.
Potential Financial Conflicts of Interest:Consultancies: D.J. Ahnen (EXACT Sciences), J.E. Allison (Fujirebio, Quidel). Stock ownership or options (other than mutual funds): J.E. Allison (IntelligeneScan). Grants received: T.R. Levin (EXACT Sciences), M.P. Lance (National Institutes of Health), M.J. Lawson (EXACT Sciences). The Mayo Clinic is a minor equity investor in EXACT Sciences.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Ms. Devens (email@example.com).
Requests for Single Reprints: David A. Ahlquist, MD, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Ahlquist, Sargent, and Loprinzi; Ms. Devens; Mr. Harrington; and Ms. Hillman: Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905.
Dr. Levin: Kaiser Permanente, 3505 Broadway, 12th Floor, Oakland, CA 94611-5714.
Dr. Rex: University of Indiana, Division of Gastroenterology/Hepatology, 550 North University Boulevard, UH 4100, Indianapolis, IN 46202.
Dr. Ahnen: University of Colorado Health Sciences Center, Denver VAMC 111E, 1055 Clermont Street, Denver, CO 80220.
Dr. Knigge: Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, PV-310, Division of Gastroenterology, Portland, OR 97239.
Dr. Lance: University of Arizona Health Science Center, 1515 North Campbell Avenue, Room 2964, PO Box 245028, Tucson, AZ 85724-5024.
Dr. Burgart: Hospital Pathology Associates, PA, Abbott Northwestern Hospital, 800 East 28th Street, Minneapolis, MN 55407.
Dr. Hamilton: University of Texas, Box 85, Room GI.3754, 1515 Holcombe Boulevard, Houston, TX 77030-4095.
Dr. Allison: Kaiser Permanente, 3505 Broadway, 7th Floor, Oakland, CA 94611-5714.
Dr. Lawson: Kaiser Permanente, 2025 Morse Avenue, 2nd Floor, Sacramento, CA 95825-2112.
Author Contributions: Conception and design: D.A. Ahlquist, D.J. Sargent, C.L. Loprinzi, T.R. Levin, K. Knigge, M.P. Lance, J.E. Allison, M.E. Devens, S.L. Hillman.
Analysis and interpretation of the data: D.A. Ahlquist, D.J. Sargent, D.K. Rex, D.J. Ahnen, K. Knigge, M.P. Lance, L.J. Burgart, S.R. Hamilton, J.E. Allison, J.J. Harrington, S.L. Hillman.
Drafting of the article: D.A. Ahlquist, D.J. Sargent.
Critical revision of the article for important intellectual content: D.A. Ahlquist, D.J. Sargent, C.L. Loprinzi, T.R. Levin, D.K. Rex, D.J. Ahnen, M.P. Lance, J.E. Allison, M.J. Lawson.
Final approval of the article: D.A. Ahlquist, D.J. Sargent, T.R. Levin, D.K. Rex, D.J. Ahnen, M.P. Lance, S.R. Hamilton, J.E. Allison, M.J. Lawson.
Provision of study materials or patients: D.A. Ahlquist, D.J. Sargent, T.R. Levin, D.K. Rex, D.J. Ahnen, M.P. Lance, M.E. Devens.
Statistical expertise: D.J. Sargent, S.L. Hillman.
Obtaining of funding: D.A. Ahlquist, D.J. Sargent, C.L. Loprinzi, M.P. Lance, M.E. Devens.
Administrative, technical, or logistic support: D.A. Ahlquist, D.J. Sargent, C.L. Loprinzi, D.K. Rex, D.J. Ahnen, K. Knigge, S.R. Hamilton, M.E. Devens, J.J. Harrington, S.L. Hillman.
Collection and assembly of data: D.J. Sargent, T.R. Levin, D.K. Rex, D.J. Ahnen, K. Knigge, M.P. Lance, L.J. Burgart, M.J. Lawson, M.E. Devens, J.J. Harrington, S.L. Hillman.
Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting.
To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm).
Blinded, multicenter, cross-sectional study.
Communities surrounding 22 participating academic and regional health care systems in the United States.
4482 average-risk adults.
Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy.
Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030).
Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers.
Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
Ahlquist DA, Sargent DJ, Loprinzi CL, Levin TR, Rex DK, Ahnen DJ, et al. Stool DNA and Occult Blood Testing for Screen Detection of Colorectal Neoplasia. Ann Intern Med. ;149:441–450. doi: 10.7326/0003-4819-149-7-200810070-00004
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Published: Ann Intern Med. 2008;149(7):441-450.
Cancer Screening/Prevention, Colorectal Cancer, Gastroenterology/Hepatology, Gastrointestinal Cancer, Hematology/Oncology.
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