INTRODUCTION
Colorectal cancer (CRC) is the third most diagnosed cancer in men and the second most diagnosed in women worldwide, causing approximately 900000 deaths annually[1], and with the majority of cases occurring in individuals over the age of 50[2]. Lack of screening and equivocal presenting symptoms often lead to diagnoses at advanced stages and poor prognosis, with limited therapeutic options[3]. CRC incidence has been steadily increasing globally, particularly in younger ages and in countries adopting a "Western" lifestyle[2,3] indicating the influence of modifiable risk factors rather than heredity. The incidence in adults aged 40–49 years has risen by almost 15% between 2000 and 2016, and it is estimated that 10.5% of new cases occur in individuals under the age of 50[4]. Incidence rates are higher in Europe, Australia, and New Zealand, while mortality rates are higher in Eastern Europe. By 2040, the burden of CRC is expected to increase by 60% and the number of deaths by 73%.
CRC SCREENING
The goal of CRC screening is to reduce mortality by diagnosing pre-malignant lesions (e.g., polyps) or asymptomatic cancers at an early stage, when the prognosis is most favorable. This was effectively demonstrated by Agatsuma et al[5], who found that cancers detected through screening and during routine hospital visits were identified at an earlier stage than those detected through symptomatic visits. Despite the wealth of literature and existing guidelines, adherence to CRC screening remains suboptimal. In the Europe, adherence rates range from 19% in Croatia and the Czech Republic to 69% in the Basque region of Spain[2]. In Canada, the average adherence rate is 55%. In the United States, where adherence is nearly 50%, the most recent guidelines recommend beginning screening at the age of 45[4]
COST-EFFECTIVENESS
A cost-effectiveness analysis of various CRC screening modalities conducted in 2010 by Lansdorp-Vogelaar et al[6] concluded that all strategies were cost-effective or even cost-saving compared to no screening[6]. A decade later, Khalili et al[7] reported similar findings[7]; however, both reviews noted a lack of consensus on determining the optimal screening technique. The authors commented on the variations between countries regarding screening costs, resource capacity, and population preferences in the selection of screening tests. These differences also extend to regions within the same country, such as rural versus metropolitan areas.
SCREENING MODALITIES
To effectively engage a large portion of the screen-eligible population, screening tests must possess the following characteristics: Clinical relevance, sensitivity, specificity to treatment effects, reliability, practicality, and simplicity. Common CRC screening tests include sigmoidoscopy, colonoscopy, computed tomography colonography, fecal occult blood test (FOBT), fecal immunochemical test (FIT), stool DNA test, and double-contrast barium enemas. For individuals aged 50–74 years without a strong family history of CRC, a combination of conventional endoscopy and FOBT is most commonly used. However, many individuals avoid colonoscopy due to feelings of embarrassment or discomfort with the invasive nature of the procedure, as well as discomfort during the preparation and examination phase[8]. Newer, non-invasive techniques like virtual colonography could become the preferred methods for this group, though they have yet to be proven cost-effective. Additionally, low-income families often struggle with the financial burden when costs are not covered by public health insurance. Tests such as FOBT and FIT are less expensive and can be conducted in specific facilities or at home. FIT is known to detect the majority of CRC cases, with summary estimates of sensitivity in meta-analyses ranging from 70% to 80%[9].
There are currently a few Food and Drug Administration-approved screening and diagnostic tests that target biomarkers in stool or blood samples (ctDNA). The next-generation multitarget stool DNA test exhibits higher sensitivity for detecting CRC and advanced precancerous lesions compared to FIT but has lower specificity[10]. Liquid biopsy is a relatively low-cost, non-invasive screening modality for CRC that requires limited technical expertise and may facilitate not only early diagnosis but also monitoring of disease progression and response to treatment. Chung et al[11] recently published a novel cell-free blood-based DNA test that demonstrated 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population[11].
AWARENESS AND ADHERENCE TO SCREENING
Targeted healthcare and community-based interventions have proven effective in raising awareness and increasing adherence to CRC screening. Most interventions focus on improving individuals' access to existing health resources, while others promote lifestyle changes[12]. Strategies to enhance rescreening rates, modality modifications, and follow-up of patients with abnormal results have also been explored. For instance, a ctDNA blood test may be a suitable option to maintain screening adherence in individuals who do not participate in screening with the FIT[13]. Osborne et al[14] demonstrated that individuals facing greater disadvantages — such as those who are unemployed or less educated, and those with prior unpleasant screening experiences — are more likely to discontinue screening[14]. Clinical trials screening the general public for various diseases have shown a preference for blood tests over stool- and urine-based tests. Deibel et al[14] suggested that a screening model with moderate effectiveness but higher adherence, requiring more frequent tests (e.g., annual or biennial), could yield better outcomes in terms of mortality and prognosis than a more traditional model like colonoscopy, even with its longer intervals (e.g., every 5 or 10 years)[15].
CONCLUSION
CRC screening programs should tailor their approaches to the specific characteristics of each community, including epidemiological features, resources, and capacity. This should include considerations for individuals who avoid regular healthcare visits due to perceptions, low income, or access difficulties. Electronic databases can facilitate the collection of information on the population's medical history and screening habits (e.g., mammography, prostate antigen) to formulate essential recommendations within the framework of a structured preventive medicine policy. In conclusion, improving adherence rates requires implementing awareness strategies, outreach programs, population education, accessible screening options, and a shift from conventional endoscopy to non-invasive techniques as first-line screening, particularly in high-risk groups and areas with low screening rates or limited resources.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: Royal College of Surgeons of England, 9021866.
Specialty type: Gastroenterology and hepatology
Country of origin: Greece
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Jin CZ, China S-Editor: Li L L-Editor: A P-Editor: Chen YX