TY - JOUR
T1 - Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening
T2 - A Diagnostic Test Accuracy Study
AU - de Klaver, Willemijn
AU - Wisse, Pieter H. A.
AU - van Wifferen, Francine
AU - Bosch, Linda J. W.
AU - Jimenez, Connie R.
AU - van der Hulst, René W. M.
AU - Fijneman, Remond J. A.
AU - Kuipers, Ernst J.
AU - Greuter, Marjolein J. E.
AU - Carvalho, Beatriz
AU - Spaander, Manon C. W.
AU - Dekker, Evelien
AU - Coupé, Veerle M. H.
AU - de Wit, Meike
AU - Meijer, Gerrit A.
N1 - Funding Information: Financial Support: By a Stand Up to Cancer/Dutch Cancer Society International Translational Cancer Research Dream Team Grant. Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research [SU2C–AACR–DT1415, MEDOCC]. Support for this study was also provided by the Dutch Digestive Foundation and was cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships (LSHM15040 and LSHM18032-SGF). Health-RI is acknowledged for providing enabling research infrastructure. The study was done within the frame of the European Cooperation in Science and Technology (COST) Action (CA17118) and supported by COST. Publisher Copyright: © 2021 American College of Physicians. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. Design: Diagnostic test accuracy study. Setting: Colonoscopy-controlled series. Participants: Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769). Measurements: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. Results: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. Limitation: Study population is enriched with persons from a referral population. Conclusion: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for populationbased CRC screening. A prospective screening trial is in preparation.
AB - Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. Design: Diagnostic test accuracy study. Setting: Colonoscopy-controlled series. Participants: Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769). Measurements: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. Results: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. Limitation: Study population is enriched with persons from a referral population. Conclusion: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for populationbased CRC screening. A prospective screening trial is in preparation.
UR - http://www.scopus.com/inward/record.url?scp=85117425837&partnerID=8YFLogxK
U2 - https://doi.org/10.7326/M20-8270
DO - https://doi.org/10.7326/M20-8270
M3 - Article
C2 - 34280333
SN - 0003-4819
VL - 174
SP - 1224
EP - 1231
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 9
ER -