Colon Cancer Screening Methods: 2023 Update

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TL;DR

This review summarizes current colorectal cancer screening modalities, including stool-based tests, radiologic imaging, and endoscopic exams, highlighting their varying sensitivities and specificities. Colonoscopy remains the gold standard for detection and prevention, but non-invasive tests like FIT and mts-DNA offer alternative options with trade-offs in accuracy and cost. The paper emphasizes the importance of early detection and the need for high-quality screening to reduce CRC mortality.

Full summary

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**Background:** Colorectal cancer (CRC) is the fourth most prevalent cancer globally, accounting for 10% of new cancer cases and approximately 550,000 deaths per year. The development of CRC involves alterations in colonic epithelium, including adenomatous polyps that accumulate genetic and epigenetic mutations. Risk factors include age, inflammatory bowel disease, sedentary lifestyle, obesity, poor diet, smoking, and alcohol consumption. Screening aims to detect early-stage CRC and remove precancerous polyps, with the goal of reducing mortality. The American Cancer Society recommends routine screening for average-risk adults starting at age 45, with colonoscopy as the gold standard. This review provides an overview of current screening options, including biomarkers, highlighting benefits and challenges of each modality.

**Methods:** This is a narrative review summarizing published literature on CRC screening methods. The authors surveyed open-access research journals from 2007 to 2023, focusing on studies in English. They describe various screening tests: invasive (colonoscopy, flexible sigmoidoscopy) and non-invasive (fecal occult blood test [FOBT], fecal immunochemical test [FIT], multitarget stool DNA test [mts-DNA], colon capsule endoscopy [CCE], CT colonography [CTC], MRI colonography [MRC]), as well as biomarkers (stool-based and blood-based). Key data from randomized trials, cohort studies, and meta-analyses are presented.

**Key Results:** - **Colonoscopy:** The gold standard for CRC screening. A randomized trial by Bretthauer et al. (2009-2014) in 55-64 year olds found that after 10 years, CRC risk was 0.98% in the invited group vs. 1.20% in usual-care group (risk reduction). CRC mortality was 0.28% vs. 0.31%. A German study showed that physicians with polyp detection rate (PDR) ≤21.8% had 69% higher proximal CRC incidence in snare polypectomy patients. AI-assisted colonoscopy improved adenoma detection rate (ADR) in a multicenter RCT. - **Flexible Sigmoidoscopy:** Reduces CRC mortality, but less effective than colonoscopy for proximal colon. Recommended every 5 years starting at age 50. - **FOBT:** Reduces CRC mortality but not incidence. A Saudi Arabian study found 19.7% positive rate, with CRC in 3.5% of abnormal pathology. - **FIT:** Sensitivity for advanced neoplasia varies by brand (25-27% for advanced adenomas, 74-81% for CRC). A Danish program uses a cutoff of 20 µg/g feces. False positive rate is 39-52%. FIT sensitivity for stage I CRC is 68%, for T1 tumors 52% (at manufacturer's cutoff). FIT is less effective for proximal colon tumors. - **mts-DNA (Cologuard):** Sensitivity for CRC 92% vs. 74% for FIT; for advanced adenoma 42% vs. 24%; specificity 87% vs. 95%. A cohort study found 73% of positive tests had colonoscopy; 1.3% had CRC, 17% advanced adenomas. Cost per advanced tumor found was $38,849. - **CCE:** Second-generation CCE has sensitivity of 84% for polyps ≥6mm and 88% for ≥10mm. Requires extensive bowel preparation. - **CTC:** High accuracy for polyps >10mm; recommended every 5 years. Radiation risk estimated at 0.14% for 50-year-olds. - **MRC:** Low sensitivity for small polyps; no radiation. - **Biomarkers:** Stool-based markers include SFRP2 methylation (high specificity), vimentin methylation (90% specificity for proximal colon), and TFPI-2. Blood-based markers include SEPT9 (better sensitivity than FIT for CRC but lower for advanced adenomas). Prognostic markers include APC, MLH1 methylation, VEGF, p53 mutations, IMP3, and SMAD4.

**Clinical Implications:** The review underscores that colonoscopy remains the most effective screening tool for CRC prevention and early detection, but its invasiveness and cost limit uptake. Non-invasive tests like FIT and mts-DNA offer alternatives, but with lower sensitivity for early-stage cancers and proximal lesions. False positives from FIT and mts-DNA lead to unnecessary colonoscopies and healthcare costs. The choice of screening modality should consider patient preference, risk factors, and resource availability. Emerging technologies like AI-assisted colonoscopy and CCE may improve detection rates. Biomarkers hold promise for early detection and prognosis, but further validation is needed. The review highlights the need for high-quality screening programs to reduce CRC mortality globally.