EVALUATING PERFORMANCE OF COMBINED HEMOGLOBIN AND TRANSFERRIN DETECTION IN FECAL IMMUNOCHEMICAL TESTING FOR COLORECTAL NEOPLASIA
DOI:
https://doi.org/10.15407/exp-oncology.2025.02.238Keywords:
colorectal cancer; fecal immunochemical test; hemoglobin; transferrinAbstract
Background. Evidence-based screening strategies can substantially reduce colorectal cancer (CRC) mortality. While colonoscopy is the gold standard, its invasiveness renders it less preferable as an initial screening tool. A two-step approach using a non-invasive fecal immunochemical test (FIT) followed by a confirmatory colonoscopy is gaining favor. A novel FIT that simultaneously detects fecal hemoglobin (F-Hb) and fecal transferrin (F-Tf) demonstrates variable diagnostic performance. Aim. This study compared the diagnostic performance of four screening strategies using three FITs with different cutoffs for F-Hb and F-Tf to detect neoplastic lesions in patients with suspected CRC. Materials and Methods. We conducted a cross-sectional study involving suspected CRC patients aged ≥ 18 at Hasan Sadikin Hospital, Bandung, from March 2023 to August 2023. The study included 72 clinically suspected CRC patients who underwent colonoscopy. We compared four CRC screening strategies using FITs designated as FIT-I (F-Hb ≥ 10 ng/mL), FIT-II (F-Hb ≥ 50 ng/mL), FIT-IIIa (F-Hb ≥ ≥ 100 ng/mL or F-Tf ≥ 40 ng/mL), and FIT-IIIb (F-Hb ≥ 100 ng/mL and F-Tf ≥ 40 ng/mL). Results. The FIT-IIIb strategy, which requires positive results for both markers, yielded the highest diagnostic performance for detecting neoplastic lesions, with 60.0% sensitivity, 96.6% specificity, a 93.8% positive predictive value, and a 73.7% negative predictive value. Conclusion. A dual-marker FIT detecting both F-Hb and F-Tf is a promising and effective screening tool for CRC. Future research should explore its implementation in broader populations and potential impacts on screening guidelines.
References
Siegel RL, Wagle NS, Cercek A, et al. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73:233-254. https:// doi.org/10.3322/caac.21772
Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021;149:778-789. https://doi.org/10.1002/ijc.33588
Maida M, Macaluso FS, Ianiro G, et al. Screening of colorectal cancer: present and future. Expert Rev Anticancer Ther.
;17:1131-1146. https://doi.org/10.1080/14737140.2017.1392243
Shaukat A, Levin TR. Current and future colorectal cancer screening strategies. Nat Rev Gastroenterol Hepatol.
;19:521-531. https://doi.org/10.1038/s41575-022-00612-y
de Kanter C, Dhaliwal S, Hawks M. Colorectal Cancer Screening: Updated Guidelines From the American College of Gastroenterology. Am Fam Physician. 2022;105:327-329.
Tanadi C, Tandarto K, Stella MM, et al. Colorectal cancer screening guidelines for average-risk and high-risk indi- viduals: A systematic review. Rom J Intern Med. 2024;62:101-123. https://doi.org/10.2478/rjim-2023-0038.
Jayasinghe M, Prathiraja O, Caldera D, et al. Colon cancer screening methods: 2023 update. Cureus. 2023; 15(4):e37509. https://doi.org/10.7759/cureus.37509
Lee JK, Liles EG, Bent S, et al. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med. 2014;160:171. https://doi.org/10.7326/M13-1484.
Cusumano VT, May FP. Making FIT count: maximizing appropriate use of the fecal immunochemical test for colorectal cancer screening programs. J Gen Intern Med. 2020;35:1870-1874. https://doi.org/10.1007/s11606-020- 05728-y
van der Vlugt M, Grobbee EJ, Bossuyt PM, et al. Adherence to colorectal cancer screening: four rounds of faecal immunochemical test-based screening. Br J Cancer. 2017;116:44-49. https://doi.org/10.1038/bjc.2016.399
Raginel T, Puvinel J, Ferrand O, et al. A Population-based comparison of immunochemical fecal occult blood tests for colorectal cancer screening. Gastroenterology. 2013;144:918-925. https://doi.org/10.1053/j.gastro.2013.01.042
Koo JH, Leong RWL, Ching J, et al. Knowledge of, attitudes toward, and barriers to participation of colorectal can- cer screening tests in the Asia-Pacific region: a multicenter study. Gastrointest Endosc. 2012;76:126-135. https://doi. org/10.1016/j.gie.2012.03.168
Atkin W, Cross AJ, Kralj-Hans I, et al. Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study. Health Technol Assess. 2019;23:1-84. https://doi. org/10.3310/hta23010
Hirata I. Evaluation of the usefulness of the simultaneous assay of fecal hemoglobin (Hb) and transferrin (Tf) in colorectal cancer screening - for the establishment of the Hb and Tf two-step cutoff assay (HTTC assay). Diagnosis (Berl) 2020;7:133-139. https://doi.org/10.1515/dx-2019-0049
Chen J-G, Cai J, Wu H-L, et al. Colorectal cancer screening: comparison of transferrin and immuno fecal occult blood test. World J Gastroenterol. 2012;18:2682.
Lansdorp-Vogelaar I, Meester R, de Jonge L, et al. Risk-stratified strategies in population screening for colorectal cancer. Int J Cancer. 2022;150:397-405. https://doi.org/10.1002/ijc.33784
White A, Ironmonger L, Steele RJC, et al. A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK. BMC Cancer. 2018;18:906. https://doi. org/10.1186/s12885-018-4786-7
Rossi M, Jahanzaib Anwar M, Usman A, et al. Colorectal cancer and alcohol consumption—populations to mol- ecules. Cancers. 2018;10:38. https://doi.org/10.3390/cancers10020038
Baraibar I, Ros J, Saoudi N, et al. Sex and gender perspectives in colorectal cancer. ESMO Open. 2023;8:101204. https://doi.org/10.1016/j.esmoop.2023.101204
Petrelli F, Tomasello G, Borgonovo K, et al. Prognostic survival associated with left-sided vs right-sided colon can- cer: a systematic review and meta-analysis. JAMA Oncol. 2017;3:211-219.
Lewandowska A, Rudzki G, Lewandowski T, et al. Risk factors for the diagnosis of colorectal cancer. Cancer Con- trol. 2022;29:10732748211056692. https://doi.org/10.1177/10732748211056692
Davidson KW, Barry MJ, Mangione CM, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. https://doi.org/10.1001/jama.2021.6238
Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer—A call to action. Nat Rev Clin Oncol. 2021;18:230-243. https://doi.org/10.1038/s41571-020-00445-1
Young JP, Win AK, Rosty C, et al. Rising incidence of early‐onset colorectal cancer in A ustralia over two decades: Report and review. J Gastroenterol Hepatol. 2015;30:6-13. https://doi.org/10.1111/jgh.12792
Lin JS, Perdue LA, Henrikson NB, et al. Screening for colorectal cancer: updated evidence report and systematic re- view for the US Preventive Services Task Force. JAMA. 2021;325:1978-1998. https://doi.org/10.1001/jama.2021.4417
Liu P-H, Wu K, Ng K, et al. Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncol. 2019;5:37-44. https://doi.org/10.1001/jamaoncol.2018.4280
Rosato V, Bosetti C, Levi F, et al. Risk factors for young-onset colorectal cancer. Cancer Causes Control. 2013;24:335- 341. https://doi.org/10.1007/s10552-012-0119-3
Gonzalez-Gutierrez L, Motiño O, Barriuso D, et al. Obesity-associated colorectal cancer. Int J Mol Sci. 2024;25:8836. https://doi.org/10.3390/ijms25168836
Li Q, Weitz J, Li C, et al. Smoking as a risk factor for colorectal neoplasms in young individuals? A systematic meta- analysis. Int J Colorectal Dis. 2023;38:114. https://doi.org/10.1007/s00384-023-04405-w
Gram IT, Park S-Y, Wilkens LR, et al. Smoking-related risks of colorectal cancer by anatomical subsite and sex. Am J Epidemiol. 2020;189:543-553. https://doi.org/10.1093/aje/kwaa005
Bai X, Wei H, Liu W, et al. Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites. Gut. 2022;71:2439-2450. https://doi.org/10.1136/gutjnl-2021-325021
Nathalia E, Theardy MS, Elvira S, et al. Downregulation of tumor-suppressor gene LHX6 in cancer: a systematic review. Rom J Intern Med. 2018;56:135-142. https://doi.org/10.2478/rjim-2018-0008
Cai J-A, Zhang Y-Z, Yu E-D, et al. Association of cigarette smoking with risk of colorectal cancer subtypes classified by gut microbiota. Tob Induc Dis. 2023;21:99. https://doi.org/10.18332/tid/168515
Huang C, Shi G. Smoking and microbiome in oral, airway, gut and some systemic diseases. J Transl Med. 2019;17:225. https://doi.org/10.1186/s12967-019-1971-7
Lee J-M, Park MJ, Heo W, et al. Clinical utility of Fecal immunochemical transferrin test in gastrointestinal bleed- ing detection. Ann Clin Microbiol. 2018;21:51-57. https://doi.org/10.5145/ACM.2018.21.3.51
Iragorri N, Spackman E. Assessing the value of screening tools: reviewing the challenges and opportunities of cost- effectiveness analysis. Public Health Rev. 2018;39:17. https://doi.org/10.1186/s40985-018-0093-8
Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhal Toxicol. 2014;26:811-828. https://doi. org/10.3109/08958378.2014.955932
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