Current colorectal cancer screening in developing countries: Identifying optimal approaches

Table 1 Summarized characteristics of colorectal cancer screening modalities

Modality	Sensitivity & specificity of advanced adenoma	Sensitivity & specificity of colorectal cancer	Participation rate (organized program)	Cost in United States dollars	Cost-effective analysis	Features
G-FOBT	Sensitivity: 0.19[30]	Sensitivity: 0.50-0.75 (95%CI: 0.09-1.0). Specificity: 0.96-0.98 (95%CI: 0.95-0.99)[28]	G-FOBT vs FIT: 46.9% vs 59.6%[35]	$4[92]	-	Qualitative tests. Samples from 3 days are needed. Diet restriction. Repeat applications are needed. It could be mailed
FIT	Sensitivity: 0.23 (95%CI: 0.20-0.25; I2 = 47.4%). Specificity: 0.96 (95%CI: 0.95-0.97; I2 = 94.8%) (at a threshold of 20 μg/g)[28]	Sensitivity: 0.74 (95%CI: 0.64-0.83; I2 = 31.6%). Specificity: 0.94 (95%CI: 0.93-0.96; I2 = 96.6%)[28]	From the first round to subsequent rounds: 48.2%, 75.3%, 83.4% and 86.1%[93]. FIT vs colonoscopy: 41.6% vs 21.9% (P < 0.01)[41]	$18[92]	ICER: Annual FIT: $14300/QALY, biennial FIT: $3970/QALY[45]	Repeat applications are needed. It could be mailed
mt-sDNA	Sensitivity: 0.43 (95%CI: 0.40-0.46). Specificity: 0.89 (95%CI: 0.86-0.92)[28]	Sensitivity: 0.93 (95%CI: 0.87-1.0). Specificity: 0.84 (95%CI: 0.84-0.86)[28]	71%[94]	$509[92]	ICER: $27500 per QALY[45]. Lower cost-effectiveness compared with no screening, but higher than colonoscopy, FS, CTC every 5 years, and annually FIT[44,45]	Repeat applications are needed
Colonoscopy	Sensitivity: 0.95 (95%CI: 0.77-1.00). Specificity: 0.89 (95%CI: 0.86-0.91) (compared with a reference standard of CTC for adenomas 10 mm or larger)[59]	-	21.9%[41]	$1891[92]	Lower cost-effectiveness compared with no screening[49,50]. ICER for single colonoscopy: $28071 per LYG[23]	Serious adverse events: 3.1 perforations (95%CI: 2.3-4.0) per 10000 procedures; 14.6 major bleeding events (95%CI: 9.4-19.9) per 10000 procedures[28]. Require bowel preparation
FS	-	-	63.1%[95]	$789[92]	Lower cost-effectiveness compared with no screening[44,50]. ICER for FS: Below $28,000 per QALY[44]	Serious adverse events: 0.7/10000 procedures[28]
CTC	Laxative-free CTC, ≥ 10 mm: Close to optical colonoscopy; ≥ 6 mm: Sensitivity: 0.59, specificity: 0.94[59]. CTC with bowel preparation, ≥ 6 mm: Sensitivity: 0.73-0.98; specificity: 0.80-0.93[28]	-	5.78%[59]	$477 (without contrast). $573 (with contrast)[92]	Lower cost-effectiveness compared with no screening. Higher cost-effectiveness compared with FIT, FS and colonoscopy[44]	Little to no risk of serious adverse events. low-dose ionizing radiation (0.8-5.3 mSv) exposure allergy[28]
mSeptin9	Epi proColon: Sensitivity: 0.64 (95%CI: 0.48-0.77)[64,65]	Epi proColon: Sensitivity: 0.68 (95%CI: 0.53-0.80). Specificity: 0.80 (95%CI: 0.78-0.82)[64,65]. Epi proColon 2.0: Sensitivity: 0.71-0.95. Specificity: 0.81-0.99[66]	-	$192[68]	-	-
Cell-free DNA blood-based test (Shield)	Sensitivity: 0.13. Specificity: 0.89[68]	Sensitivity: 0.83[68]	-	$949[23]	Higher cost-effectiveness than no screening. ICER: $377538 per LYG[23]	-

G-FOBT: Guaiac-based fecal occult blood test; FIT: Fecal immunochemical test; FS: Flexible sigmoidoscopy; CTC: Computed tomographic colonography; ICER: Incremental cost-effectiveness ratio; QALY: Qualified-adjusted-life-year; LYG: Life-year-gained.

Table 2 Summarized guidelines for colorectal cancer screening from different regions

Country/association	Target group	Recommendation	Average risk person definition
USPTF, 2021[28]	Asymptomatic adults at average risk of colorectal cancer. 50-75 years (A recommendation). 45-49 years (B recommendation)	High-sensitivity G-FOBT or FIT every year. sDNA-FIT every 1 to 3 years. CTC every 5 years. Flexible sigmoidoscopy every 5 years. Flexible sigmoidoscopy every 10 years + FIT every year. Colonoscopy screening every 10 years	No prior diagnosis of colorectal cancer, adenomatous polyps, or inflammatory bowel disease; no personal diagnosis or family history of known genetic disorders that predispose them to a high lifetime risk of colorectal cancer (such as Lynch syndrome or familial adenomatous polyposis)
MTSTF, 2022[96]	Average-risk adults aged 45-75 years	High-quality colonoscopy every 10 years or an annual FIT (strong recommendation; moderate-quality evidence). Flexible sigmoidoscopy every 5 years to 10 years (strong recommendation; high-quality evidence). CTC every 5 years (strong recommendation, low-quality evidence). FIT–fecal DNA every 3 years (strong recommendation, low-quality evidence) in individuals who decline colonoscopy and a FIT	Those aged 50-75 years with no history of CRC or adenoma, with no first-degree relatives with CRC, and who are not up to date with CRC screening according to other methods (that is, sigmoidoscopy within 5 years or colonoscopy within 10 years)
ACP, 2023[92]	Asymptomatic average-risk adults aged 50-75 years	A FIT or high-sensitivity G-FOBT every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a FIT every 2 years	No prior diagnosis of CRC, adenomatous polyps, or inflammatory bowel disease, and no personal diagnosis or family history of known genetic disorders that predispose a person to a high lifetime risk for CRC (for example, Lynch syndrome)
ACS, 2018[11]	Average-risk adults aged 45-75 years	Annual FIT. Annual high-sensitivity G-FOBT. mt-sDNA test every 3 years. Colonoscopy every 10 years. CTC every 5 years. Flexible sigmoidoscopy every 5 years	Persons without a history of adenomatous polyps or CRC and not at increased risk for CRC due to a family history of CRC, a confirmed or suspected hereditary CRC syndrome (such as familial adenomatous polyposis or Lynch syndrome), a personal history of abdominal or pelvic radiation for a previous cancer, or a personal history of inflammatory bowel disease
NCCN, 2024[97]	Adults aged 45-70 years	For individuals at average risk, the choice of a particular screening modality should include a conversation with the patient concerning their preference and availability, for individuals at increased risk, colonoscopy is the preferred method	Aged 45-75 years; no personal history of adenoma or SSP/SSL or CRC; no personal history of IBD; no personal history of high-risk CRC genetic syndromes (list of syndromes on CSCR-2); no personal history of cystic fibrosis; no personal history of childhood cancer; negative family history for confirmed advanced adenoma (i.e., high-grade dysplasia, 21 cm, villous tubulovillous histology) or an advanced SP/SSL, (≥ 1 cm, any dysplasia) in first-degree relatives. Negative family history for CRC
The Asia-Pacific region, 2022[98]	Adults aged 50-year. Using age alone as a cut-off point for CRC screening is insufficient. Decision should be made by patients and clinicians together based on a patient’s overall health status, prior screening history and patient’s preferences	Quantitative FIT (every year or every 2 years) or colonoscopy (every 10 years)	-
The European Colorectal Cancer Screening Guidelines Working Group, 2013[99]	Adults aged 50-74 years residing in the target area	Recommendation based on good evidence for G-FOBT, reasonable evidence for FIT and flexible sigmoidoscopy, and limited evidence for colonoscopy	-
National Cancer Center of China, 2020[100]	Low-to-average-risk adults aged 50-75 years (strong recommendation, moderate-quality evidence). High-risk adults aged 40-75 years (strong recommendation, moderate-quality evidence)	-	No first-degree relatives with a CRC diagnosis; no personal diagnosis of adenomatous polyps or CRC; no history of inflammatory bowel over 8-10 years; no positive G-GOBT results
The Canadian Association of Gastroenterology, 2018[101]	All individuals with a family history of CRC or documented adenoma. 50-75 years	Colonoscopy is suggested (recommended in individuals with ≥ 2 first-degree relatives), with FIT as an alternative	-
The Saudi Arabian Ministry of Health, 2015[102]	Average-risk adults aged 45-70 years	Colonoscopy alone every 10 years is the recommended modality; however, if unavailable, flexible sigmoidoscopy every 5 years coupled with annual G-FOBT or FIT should be considered. FIT is preferred over G-FOBT	-

USPTF: United States Preventive Services Task Force; MTSTF: The United States Multi-Society Task Force; ACP: The American College of Physicians; ACS: American Cancer Society; NCCN: The National Comprehensive Cancer Network; CRC: Colorectal cancer; G-FOBT: Guaiac-based fecal occult blood test; FIT: Fecal immunochemical test; IBD: Inflammatory bowel disease; SSP/SSL: Sessile serrated polyp/sessile serrated lesion; SP/SSL: Serrated polyp/sessile serrated lesion; mt-sDNA: Multi-target stool DNA.