ABSTRACT
Introduction
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. Nonetheless, with early detection of CRC or its precancerous lesions, mortality, and CRC incidence can be reduced. Although colonoscopy is currently the gold standard for CRC screening and diagnosis, its invasive nature, and troublesome bowel preparation deter patient participation. Therefore, there is a need to expand the use of noninvasive or minimally invasive methods to increase patient compliance.
Areas Covered
This review summarizes advances in different methods for CRC screening, including stool bacterial and metagenomic markers, fecal proteins, genetic and epigenetic markers in blood and stools, and imaging modalities. The cost-effectiveness of these methods is also discussed. FIT is more cost-effective compared to virtual colonoscopy, mSEPT9 test, and Multitarget Stool DNA test, while the cost-effectiveness of other noninvasive methods requires further evaluation.
Expert Opinion
Recent evidence has well demonstrated the usefulness of gut microbiome and certain fecal bacterial markers in the noninvasive diagnosis of CRC and its precancerous lesions. Many of the fecal biomarkers, from host cells or the gut environment, show better diagnostic sensitivity than FIT. New screening tests based on these fecal biomarkers can be expected to replace FIT with higher cost-effectiveness in the near future.
Abbreviations
AUC — Area under the Receiver Operating Characteristic curve; Bc — Bacteroides clarus; BFT — B. fragilis toxin; BMI — body mass index; CCE — colon capsule endoscopy; CEA — carcinoembryonic antigen; Ch — Clostridium hathewayi; CRC — colorectal cancer; Cs — Clostridium symbiosum; CT — computed tomography; CTC — circulating tumor cell; E. coli — Escherichia coli; eggNOG — evolutionary genealogy of genes: Non-supervised Orthologous Groups; EpCAM — epithelial cell adhesion molecule; ETBF — enterotoxigenic Bacteroides fragilis; FDA — Food and Drug Administration; FIT — Fecal immunochemical testing; Fn — Fusobacterium nucleatum; gFOBT — guaiac fecal occult blood test; ICER — incremental cost-effectiveness ratio; LST — laterally spreading colorectal tumor; M2-PK — Tumor pyruvate kinase isoenzyme M2; miRNA — microRNA; mSEPT9 — methylated SEPTIN 9 DNA; mtSDNA — multi-target stool DNA; NF-κB — nuclear factor kappa-light-chain-enhancer of activated B cells; OTUs — operational taxonomic units; P. anaerobius — Peptostreptococcus anaerobius; P. asaccharolytica — Porphyromonas asaccharolytica; PCWBR2 — putative cell wall binding repeat 2; pks — polyketide synthase; Pm — Parvimonas micra; POD — probability of disease; Ps — Peptostreptococcus stomatis; QALYG — quality-adjusted life year gained; qPCR — quantitative polymerase chain reaction; qRT-PCR — quantitative reverse transcription polymerase chain reaction; Sm — Solobacterium moorei; VC — virtual colonoscopy
Article highlights
Fecal immunochemical test and colonoscopy are currently the preferred methods for colorectal cancer screening
Novel methods of non-invasive/minimally invasive colorectal cancer screening and diagnosis include: microbial and metagenomic markers, tumor pyruvate kinase isoenzyme M2, epigenetic and genetic markers, circulating tumor cells, virtual colonoscopy and colon capsule endoscopy.
Among novel non-invasive methods, tests that detect DNA hypermethylation and mutation are more commonly used in clinical settings.
At the present stage, fecal immunochemical test is the most cost-effective method of non-invasive colorectal cancer screening and diagnosis. It is expected in the future that tests of higher accuracies and suitable costs will have an even higher cost-effectiveness than fecal immunochemical test.
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.