Colorectal cancer early screening: Dilemmas and solutions

Abstract

Colorectal cancer (CRC) is a prevalent malignancy worldwide, posing a significant public health concern. Mounting evidence has confirmed that timely early screening facilitates the detection of incipient CRC, thereby enhancing patient prognosis. Obviously, non-participation of asymptomatic individuals in screening programs hampers early diagnosis and may adversely affect long-term outcomes for CRC patients. In this letter, we provide a comprehensive overview of the current status of early screening practices, while also thoroughly examine the dilemmas and potential solutions associated with early screening for CRC. In response to these issues, we proffer a set of recommendations directed at governmental authorities and the general public, which focus on augmenting financial investment, establishing standardized screening protocols, advancing technological capabilities, and bolstering public awareness campaigns. The importance of collaborative efforts from various stakeholders cannot be overstated in the quest to enhance early detection rates and alleviate the societal burden of CRC.

Key Words: Colorectal cancer; Early screening; Asymptomatic candidates; Dilemmas; Solutions

Core Tip: Pérez-Holanda et al identified that non-participation of asymptomatic candidates in screening protocols reduced early diagnosis and compromised long-term outcomes of colorectal cancer. We focus on the topic of dilemmas and solutions of early screening for colorectal cancer and profile the current landscape of early screening, propose recommendations for governments and the public.

TO THE EDITOR

Colorectal cancer (CRC) is one of the most common malignancies worldwide, ranking third in incidence and second in mortality[1,2]. According to the latest report released by International Agency for Research on Cancer, there were close to 1.9 million new cases alongside 904000 cases death from CRC in 2022, and the mortality rate was close to 20%[2]. Despite the stabilizing trends of CRC for all ages combined, there are lots of researches identify increasing incidence of younger CRC, which is diagnosed at younger than 50 years old and defined as early-onset CRC, suggesting that incidence of CRC tend to be younger[3-7]. Studies show that most CRCs evolve gradually from precancerous lesions, such as adenomatous polyps. It is well-known that early screening is crucial for prevention and improved prognosis of CRC through detection and removal of adenomatous polyps and precancerous lesions[8-10]. However, the United States Preventive Services Task Force reported that about 26% of eligible adults in America had never been screened for CRC and 31% were not up to date with screening in 2018[11]. It is evident that the low proportion of young individuals eligible for CRC screening who actually undergo screening, as well as the non-participation of asymptomatic individuals in CRC screening, hinders the early diagnosis of CRC. Patients lack clear symptoms like hematochezia, bowel habit changes, abdominal pain, diarrhea, or obstruction during early and even locally advanced stages of CRC, hence these people are classified as asymptomatic CRC cases. Recently, Agatsuma et al’s study published at World Journal of Gastroenterology identifies that people with periodical hospital visits for comorbidities are detected CRC earlier than those without periodical hospital visits and asymptomatic candidates, but similar to the cancer screening group[12]. For instance, patients with functional gastrointestinal disorders, which characterized by gastrointestinal symptoms such as diarrhea, constipation, postprandial fullness, nausea, and vomiting, triggered by psychological and social factors, may identify CRC earlier than asymptomatic people[13]. And Pérez-Holanda’s editorial published at World Journal of Gastroenterology highlights non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of CRC[14]. It’s an elephant in the room that the low participation rate among asymptomatic individuals hampers early detection efforts and worsens prognosis of CRC. In our editorial, we focus specifically on the dilemmas and challenges facing CRC early screening and try to find a way out of the screening dilemmas on the background of rising early-onset CRC.

CURRENT LANDSCAPE of EARLY CRC SCREENING

Currently, screening modalities primarily consist of population-based and opportunistic screening approaches[10]. Population-based screening, typically government-led, targets general eligible candidates, aiming to detect early focies and asymptomatic early-onset CRC. However, it demands substantial human, material, and financial resources while faces challenges with low population adherence[15-17]. Opportunistic screening also known as individual screening, facilitated by healthcare visits, offers higher compliance and resource-savings but fails to reduce population incidence due to the exclusion of asymptomatic individuals[18,19]. Actually, the choice of screening modality is related to the country’s economic development, investment in public health services, and the population’s awareness of cancer screening. The optimal initial screening age varies across different guidelines. Western countries generally recommend screening for individuals aged 50-75, while the American Cancer Society has lowered the age to 45 in response to rising early-onset CRC[11]. Due to the high burden of CRC in China, the expert consensus on the early diagnosis and treatment of CRC in China (2023) recommends CRC screening for general individuals aged 40-74[20]. Multitudes of evidences demonstrated the primary screening age should be relaxed for those at high risk, such as immediate family members with CRC, microsatellite instability-high or deficient mismatch repair and other germline variant (Table 1)[21-26]. For instance, individuals at high risk for Lynch syndrome should receive early screening at ages 20-25 years or 2-10 years earlier than the youngest age of CRC in the family[27,28], while colonoscopy screening is recommended for those at high risk of familial adenomatous polyposis syndrome as early as 10-18 years of age[29,30]. At present, the main methods for early screening of CRC include high-risk factor questionnaire, Asia-pacific colorectal screening score (APCS score)[31,32], fecal immunochemical test (FIT)[33], multi-target fecal DNA detection[34,35], circulating tumor cell[34], computerized tomography virtual colonoscopy and total colonoscopy[10]. The APCS score is predicated on fundamental clinical data, including age, gender, family history, and smoking status, which can be utilized by family physicians, healthcare providers, and nurse educators[31,36]. Furthermore, a clinical trial of CRC screening comprising 9989 subjects confirmed that the sensitivity and specificity of FIT in detecting CRC were 73.8% and 94.9%, respectively[34,35]. Therefore, the risk stratification combined FIT based on questionnaire survey or APCS score is a widely used screening strategy, which has high feasibility and cost-effectiveness in large-scale population screening[37,38]. Nevertheless, colonoscopy is still the gold standard of CRC screening and has high sensitivity and specificity for the diagnosis of CRC[9,39].

Table 1 Familial high-risk diseases associated with colorectal cancer.

Diseases	Mutation	CRC incidence	Risk	Description
Lynch syndrome[21]	mismatch repair genes such as MLH1, MSH2, MSH6, or PMS2	50%-80%	High	A hereditary condition linked to mutations in mismatch repair genes. It significantly increases the risk of colorectal cancer, often at a younger age, and is also associated with other cancers like endometrial and ovarian cancers
Familial adenomatous polyposis[22]	APC gene	100%	High	An autosomal dominant disorder caused by mutations in the APC gene, leading to the development of numerous adenomatous polyps in the colon and rectum. If untreated, nearly all individuals with familial adenomatous polyposis will develop colorectal cancer by the age of 40-50 years
MUTYH-associated polyposis[23]	MUTYH gene	43%-100%	High	A condition similar to familial adenomatous polyposis, but caused by mutations in the MUTYH gene, which also leads to the development of colorectal polyps and an increased risk of colorectal cancer
Peutz-Jeghers syndrome[24]	STK11 (LKB1) gene	NA	High	A genetic disorder characterized by the presence of hamartomatous polyps in the gastrointestinal tract and an increased risk of colorectal cancer, as well as other cancers such as breast and ovarian cancers
Juvenile polyposis syndrome[25]	SMAD4 or BMPR1A gene	17%-68%	High	A hereditary condition marked by the development of numerous juvenile polyps in the gastrointestinal tract, which can progress to colorectal cancer
Constitutional mismatch repair deficiency[26]	mismatch repair genes	NA	High	A rare, autosomal recessive condition caused by biallelic mutations in mismatch repair genes, leading to early-onset colorectal cancer and other cancers, often before the age of 20 years

NA: Not applicable.

CHALLENGES and DILEMMAS in EARLY SCREENING

Despite the well-established and widely recognized evidence that early screening can significantly decrease the morbidity, a multitude of substantial challenges and formidable dilemmas persist and prevail in the early screening of CRC worldwide. First, the issue of screening modalities selection. Population screening can be widely targeted at asymptomatic people to detect asymptomatic early-onset CRC as early as possible. However, the investment of manpower, material resources and financial resources in population screening is huge, and the participation and compliance of the population is low[15,40]. At the same time, although opportunistic screening has high population compliance and saves some medical resources at the same time, it cannot reduce the incidence rate of the population because multitudinous asymptomatic people will not be included in the screening[41,42]. Second, the issue of individualization of screening methods and standardization of the screening procedure. At present, there are many methods of CRC screening, but how to choose the optimally personalized screening method for individuals requires further research[43]. At the same time, the screening processes in various countries and regions have not been unified, which poses obstacles to the research and international exchanges on early screening of CRC. Third, the lack of early screening publicity and education leads to insufficient awareness and attention of the population to CRC screening[44]. Since most of the early-onset CRC does not have typical symptoms, the screening participation and compliance of the asymptomatic population are low. The low awareness of the people about the screening method, and the misunderstanding and fear of the invasive inspection method lead to a further reduction in the actual participating population[45]. Fourth, there are differences in economic development and uneven distribution of medical resources in various places. Since early screening requires health education and resource investment, but the economic development in various countries and regions is unbalanced, resulting in an uneven distribution of medical resources[41]. In economically underdeveloped areas, the accessibility of early screening technologies is poor, and the quality of related screening technologies also needs to be improved. Having thoroughly explored the various challenges that impede the early screening of CRC globally, it is evident that a multifaceted solution is required to enhance the effectiveness of screening programs. The following recommendations aim to provide a comprehensive framework for improving CRC screening.

RECOMMENDATIONS for OVERCOMING SCREENING DILEMMAS

Enhancing the early screening rate of CRC is crucial for improving patient prognosis. Firstly, the government must take a leading role in promoting early CRC screening through targeted public education campaigns and increased funding for screening initiatives. By allocating resources strategically, particularly to underserved areas, equal access to screening can be achieved. Secondly, a hybrid approach combining population-based and opportunistic screening can be employed to maximize coverage and detection rates. Population screening can be focused on high-risk groups or implemented more broadly in well-resourced areas, while opportunistic screening can be integrated into routine medical examinations. Furthermore, establishing standardized screening procedures is crucial for consistency and quality. This includes developing clear guidelines for screening methods, intervals, and follow-up procedures, as well as investing in research to improve existing techniques and develop new non-invasive alternatives. We have provided a proper procedure of CRC early screening (Figure 1). Additionally, raising public awareness and encouraging active participation in screening is essential. Educational campaigns should emphasize the importance of early detection, the simplicity of modern screening methods, and the potential consequences of delayed screening, particularly for asymptomatic individuals. In summary, while the challenges facing CRC early screening are significant, the proposed recommendations offer a roadmap for improving screening rates, facilitating earlier detection, and ultimately reducing the morbidity and mortality associated with CRC.

Figure 1 Procedure of colorectal cancer early screening. For the eligible population to be incorporated into the screening procedure, the combination of population-based screening and opportunistic screening is adopted. Risk stratification was carried out by evaluating risk factors and then individualized screening programs are selected. APCS: Asia-Pacific colorectal screening; FIT: Fecal immunochemical test; CRC: Colorectal cancer; LS: Lynch syndrome; FAP: Familial adenomatous polyposis syndrome; MAP: MUTYH-associated polyposis; PJS: Peutz-Jeghers syndrome; JPS: Juvenile polyposis syndrome; CMMR-D: Constitutional mismatch repair deficiency.

CONCLUSION

The low participation rate in CRC early screening, particularly asymptomatic individuals, significantly impacts early detection and treatment. Addressing the dilemmas outlined in this article requires collaboration between governments and the public. By implementing the proposed recommendations, we can improve early detection, reduce CRC overall burden, and ultimately save lives.