Role of a noninvasive stool-based molecular test in screening and early detection of colorectal cancers

Abstract

Background: Colonoscopy is considered the gold standard for most currently established screening programs for colorectal carcinoma (CRC), but due to its invasive nature, there were several emerging needs for the use of a substitutive, sensitive, non-invasive triaging modalities, such as utilizing immunochromatographic fecal occult blood tests (IFOBT) or molecular stool based tests such as Glycolytic M2-Pyruvate Kinase (M2-PK). Objectives: Firstly, to evaluate the sensitivity of a molecular stool based (M2PK) test, as a non-invasive, screening modality for detecting CRC and other colorectal disease (CRD). Secondary, to insight the current prevalence of CRC precursors in the Kingdom of Bahrain and recommend a customized age of enrollment in National Screening Program for CRC, once established and Thirdly, to compare the sensitivity of this fecal tumor marker based M2-PK test, as a potential replacement for the currently used IFOB test, in an attempt to promote for the need to establish a National Screening Program for Colorectal Cancer (NSPCC) based on such molecular based test or a similar platform in the kingdom, much comparable to the currently established international screening programs. Design: Prospective, cross sectional study. Duration and Place of Study: July 2012-December 2016, King Hamad University Hospital (KHUH), Bahrain. Sample Size: 2,100 (Based on Bahrain Population statistics: 1,248.348. Materials and Methods: The stool samples were collected shortly after launching a nationwide public awareness campaign against CRD in all major governmental and private sector hospitals and clinics. Out of the intended 2100 target samples, 1074 individuals managed to go through the well-structured distributed questioner and have been selected according to the inclusion/exclusion criteria and submitted their stools' samples for the detection of any CRD. A combined (molecular M2-PK and IFOBT) stool tests were used to detect any CRD in all examined stool samples. A total of 105 M2-PK' positive and 85 M2-PK'negative individuals underwent a subsequent specialist consultation and a fast track colonoscopy. Results: Out of the intended 2100 study sample, 1552 Participants were obtained during the study period and out of those, 1199 have been selected based on the inclusion and exclusion criteria. The no-show selected participants were 624 and only 575 individuals have submitted their Stool samples along with fully completed questioners. Out of those 575, only 287 stool samples were positive with M2-PK test, while 197 of the same stool samples were positive with IFOBT. Among these positive cases, only 105 of participants agreed after their medical consultation to undergo for full colonoscopies and biopsies for microscopic examination. These 105 successful full colonoscopies reveled 85 (81%) individuals negative for any neoplastic lesion and only 20 individuals (19%) showed neoplastic lesion. These 20 neoplastic findings included, 17 (85%) adenomatous polyps, 02 (10%), adenocarcinomas, and 01 (5%) was neuroendocrine carcinoma. The 17 adenomatous polyps were 09 tubular adenomas, 01 villous adenoma, and 07 tubulovillous adenomas. The colonoscopy findings in those (85) negative cases for neoplastic lesion were (6) hemorrhoids, (13) hyperplastic polyps, (10) normal mucosae with normal biopsies, (9) diverticulosis, (1) angiodysplasia, (1) inflammatory bowel disease and (1) solitary rectal ulcer. Conclusion: The screening of CRC by Stool Based molecular test such M2-PK showed high sensitivity for the detection of neoplastic Colorectal lesions compared to IFOBT. The study also found that stool based molecular (M2-PK) test, is a rapid, non-invasive, and convenient technique, which can be used as a platform for a forthcoming CRC National Screening Program in the Kingdom of Bahrain.