National cancer screening program for colorectal cancer in Korea

Cancer is the leading cause of death in South Korea, and colorectal cancer (CRC) ranks 3rd among all cancer-related deaths in the country [1, 2, 3, 4, 5, 6, 7]. In 2021, 82,688 people died from cancer (International Classification of Diseases [ICD] C00-C97), accounting for 26.0% of all deaths [8]. To improve cancer survival and facilitate early diagnosis, the Ministry of Health and Welfare of Korea has implemented the National Cancer Screening Program (NCSP) since 1996 [9]. The NCSP officially aims to detect cancer at an early stage, to guide treatment, improve cure rates, and increase survival rates (Fig. 1). Programs are in place to ensure that people can be examined every year or every 2 years for the early diagnosis of stomach, liver, colon, breast, and cervical cancers.

Fig. 1
Annual colorectal cancer incidence and mortality rates in South Korea. The number of colorectal cancer patients in Korea has increased from about 10,000 in 1999 to about 30,000 in 2021, but the number of deaths has increased more slowly, from about 3,700 in 1999 to about 8,900 in 2021.

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In general, the classification code for cancer registration uses the ICD for Oncology published by the World Health Organization, and the Korean National Cancer Registry also collects data according to this classification and publishes an annual report. According to the 2020 Cancer Statistics published in December 2022, the number of cancer cases in 2020 was 247,952, with an incidence rate of 482.9 per 100,000. Over the years in which cancer statistics have been collected, cancer prevalence rates have continued to increase. However, unusually, the 2020 statistics showed a slight decrease of 3.6% compared to those from the previous year. We cannot exclude the impact of the unprecedented coronavirus disease 2019 pandemic and believe that this decline is a worthy reason to reconsider changes in the national cancer screening rate.

The prevalence of CRC remains high, ranking 3rd among the total population, 4th among men, and 3rd among women. The results show that CRC is the leading cause of cancer among women in the post-64-year age group [10], which is of particular significance considering the continued increase in female life expectancy [6].

This review aimed to investigate the NCSP for CRC and assess its impact in terms of advancing public health. It was approved by the Institutional Review Board of Ewha Womans University Mokdong Hospital (No. EUMC 2023-08-038).

The purpose of cancer screening is to detect cancer at an early stage in the general population who are asymptomatic, to maximize early treatment and cure, reduce the national healthcare cost burden of advanced cancer, and improve public wellness. Considering the high prevalence and severity of CRC, most healthcare providers are concerned about whether screening programs are effective. As screening tests require significant resources and can be costly when implemented nationwide, they are typically adopted after a thorough assessment of their efficacy. Consequently, each country may employ a slightly different screening approach tailored to its specific circumstances (Table 1[11, 12, 13, 14, 15, 16, 17]). In Korea, the NCSP is a nationwide initiative aimed at increasing cancer cure rates and reducing cancer-related mortality. The government is enacting the NCSP for all individuals covered by health insurance and all recipients of medical benefits, with the goal of mitigating societal expenses, including the rising healthcare costs associated with cancer.

Table 1
Colorectal cancer screening guidelines around the world

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The Korea Central Cancer Registry (KCCR) was established at the National Medical Center in 1980, as a hospital-based nationwide cancer registry initiated by the Ministry of Health and Welfare. The KCCR started the cancer registration project with the voluntary participation of hospitals and later expanded this to nationwide medical institutions where cancer can be diagnosed and treated. The KCCR was transferred to the National Cancer Center in September 2000 and was designated the Central Cancer Registry under the Cancer Control Act in December 2004. The goal of the cancer registration project was to calculate cancer registration statistics in Korea and to identify priorities for cancer control policies. Cancer registration statistics offer several valuable applications, including the ability to anticipate future healthcare needs, such as the number of doctors, hospitals, and associated costs required for cancer treatment. They also enable the detection of cancer trends and outbreaks, thereby facilitating the identification of potential cancer causes. These statistics further aid in assessing the cancer burden within specific geographic regions using regional cancer data. Additionally, they serve as means to evaluate the effectiveness of newly implemented cancer prevention, diagnosis, and treatment initiatives and can be utilized as educational and promotional resources for cancer awareness and education.

For more efficient policy formulation and implementation, the Korean government enacted the Cancer Control Act of 2003, which stated that medical practitioners and heads of medical institutions must actively cooperate with cancer control projects executed by the national and local governments (hereinafter referred to as “cancer control projects”). The NCSP began screening for stomach, breast, and cervical cancers in 1999, followed by liver cancer in 2003, and CRC in 2004. Since July 2019, lung cancer has been included, so the program now screens for 6 cancers. This is conducted every 2 years for stomach and breast cancer patients aged 40 years and older, and once a year for CRC patients aged 50 years and older. Liver cancer screening is performed twice a year for high-risk groups, such as hepatitis carriers over the age of 40 years, and cervical cancer screening is performed once every 2 years from the age of 20 years.

The Ministry of Health and Welfare of Korea has recommended annual fecal immunochemical testing (FIT) for people aged 50 years and older as the first step in CRC screening since 2004. Those with a positive FIT are scheduled to undergo colonoscopy or double-contrast barium enema as the second step, while those with a negative fecal occult blood test (FOBT) are not offered colonoscopy [9].

Recently, Park et al. [18] reported 14 years of NCSP data for CRC in Korea. According to their report, the number of participants screened and invited to undergo CRC screening increased from 6,046,304 and 441,392 in 2004 to 18,929,321 and 5,770,617 in 2017, respectively, while the rate of screening of participants also increased from 7.3% in 2004 to 32.7% in 2011. It decreased to 24.7% in 2012 and increased to 30.5% in 2017 [18]. The number of follow-up screening tests using colonoscopy increased from 6,966 of 33,173 (21.0%) in 2004, to 73,056 of 229,779 (31.8%) in 2017. Participation rates were the highest among those in their 60s. Nevertheless, the participation rate among those in their 50s has been significantly lower than that of participants aged 60–79 years since 2011, which suggests that people in their 50s may not be aware of their risk because they are not as concerned that they may develop CRC. The most efficient approach to promoting active engagement in screening programs is to inform the public about the disease and to convey the effectiveness of these screening programs actively.

For an effective screening program, tests should be conducted at the most effective frequency in populations with a high incidence of CRC. The test method should ideally be simple to perform, simple to interpret, and inexpensive, to facilitate mass tests.

The adenoma-carcinoma sequence in the development of CRC is generally accepted, with most agreeing that the removal of adenomas reduces the frequency of CRC. This indicates that CRC screening should encompass the identification of both carcinomas and adenomas to be considered comprehensive and meaningful.

Guaiac FOBT (gFOBT) is the most commonly used noninvasive screening method for CRC [19]. FOBT is simple and reasonably acceptable for screening in outpatient settings. An individual undergoing screening typically collects a stool sample at home and sends it to a laboratory. This test identifies hemoglobin molecules in the exfoliation of abnormally sloughed epithelial cells. This is one of the initial methods employed for CRC screening and remains the primary approach used. It operates by detecting changes in color when hemoglobin in the feces undergoes oxidation, relying on the pseudoperoxidase activity of hemoglobin, which promotes the oxidation of guaiac upon the addition of H₂O₂.

Based on evidence from randomized controlled trials, a screening program using a gFOBT decreased CRC mortality when used with repeated applications over time and endoscopic follow-up of positive results [20]. Hu et al. [21], in their systematic review of the FOBT, reported that the FOBT had a cost-effective impact, resulting in a reduction in CRC mortality ranging from 8% to 16%. A major limitation of the gFOBT is that the amount of oxidized hemoglobin must be detectable for the test to be reliable, and false positivity caused by substances that can cause similar oxidation reactions, such as medicines or food, cannot be excluded [22, 23].

To compensate for the weaknesses of the FOBT, the FIT has recently been actively adopted and recommended [23, 24, 25]. The FIT has been validated by the detection of antibodies specific to the globin portion of human hemoglobin [26, 27]. Since globin in the upper gastrointestinal tract is degraded by gastric juice, it is not only sensitive to bleeding in the lower gastrointestinal tract, but also has a low false-positive rate, because the test results do not change depending on the type of food. Current screening recommendations indicate a stronger preference for the FIT [28]. Table 2 presents the accuracy of the FOBT and FIT in CRC screening [29, 30, 31, 32, 33, 34, 35, 36].

Table 2
A study of the utility of the FOBT and FIT in colorectal cancer screening

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The sensitivities for detecting colorectal neoplasia and CRC ranged from 25% to 27% and 74% to 81%, respectively. This is a satisfactory screening test result [28]. Many countries have investigated the performance of the FIT in CRC screening in large patient populations. The results showed a sensitivity of approximately 47.1%–93.3% and a specificity of 83.5%–96.3%, although the performance varied slightly by country (Fig. 2) [37, 38, 39, 40, 41, 42, 43].

Fig. 2
Screening performance of the fecal immunochemical test (FIT) for colorectal cancer, by country. The sensitivity of the FIT across countries is about 47%–93% and the specificity is about 83%–96%. The sensitivity of FIT in Korea is lower than in the United Kingdom, the Netherlands, and Germany, but the range of 95% confidence intervals is wide enough that it is not considered to be underperforming compared to other countries.

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Denmark’s CRC screening program began using the FIT in 2014, offering tests every 4 years for adults aged 50–74 years, which was changed to every 2 years starting in 2018. A FIT score of 20 g/g feces was deemed positive, and citizens with positive FITs were offered colonoscopy. Recent reports have indicated a direct correlation between FIT results and the risk of CRC, suggesting that FIT results can be used to tailor screening programs on an individual basis [44].

However, false-positive and false-negative results persist. Law et al. [45] reported that female sex and hemorrhoids were associated with increased odds (with odds ratios [ORs] of 1.59 and 1.89, respectively) in relation to false-positive FITs, while increasing age and body mass index were associated with decreased odds (with ORs of 0.94 and 0.96, respectively). Niedermaier et al. [46] reported the estimated stage- and location-specific sensitivities of quantitative FIT in a large cohort of patients with CRC. They collected fecal samples from 435 CRC patients, calculated the sensitivity of the quantitative FIT, and analyzed the results based on tumor characteristics. The FIT demonstrated the following sensitivity rates for detecting different tumor stages: 52% sensitivity (95% confidence interval [CI], 37%–67%) for T1 tumors, 79% sensitivity (95% CI, 68%–88%) for T2 tumors, 93% sensitivity (95% CI, 89%–95%) for T3 tumors, and 84% sensitivity (95% CI, 72%–92%) for T4 tumors. FIT-detection of stage I cancers had 68% sensitivity (95% CI, 57%–78%), that of stage II cancers had 92% sensitivity (95% CI, 87%–96%), and that of stage III cancers had 82% sensitivity (95% CI, 73%–89%).

Heer et al. [47] conducted a systematic review of 3 relevant studies on the performance of FIT in CRC. In individuals under the age of 50 years, the overall sensitivity of FIT for advanced neoplasia was found to be 0.23 (95% CI, 0.17–0.30), with a corresponding specificity of 0.96 (95% CI, 0.94–0.98). Additionally, the sensitivity and specificity for detecting advanced adenoma among individuals under 50 years of age were 23% and 96%, respectively, based on data from 3 studies.

In many countries, the primary screening approach for CRC involves stool tests. Individuals identified through this initial screening may be recommended to undergo further evaluation through endoscopic procedures, such as colonoscopy and sigmoidoscopy. Endoscopy is limited when performed for screening purposes in asymptomatic populations. While stool tests can be gathered as an outpatient procedure and are comparatively straightforward to collect independently, endoscopy necessitates a preparatory phase (typically, sigmoidoscopy involves an enema and colonoscopy entails thorough bowel cleansing), which can be time-consuming and uncomfortable [48]. Colonoscopy-associated complications are frequently encountered. Another noteworthy limitation is that the accuracy of the test relies on the proficiency of the operator [5]. However, endoscopy offers the clear advantage of enabling the direct inspection of lesions and potential biopsy of suspicious regions. Furthermore, endoscopic resection allows the removal of polyps, thus enabling a combination of diagnosis and treatment. However, whether these advantages render it an effective method for screening the general asymptomatic population remains uncertain.

Recently, Dominitz and Robertson [49] published an editorial on screening colonoscopy. In this enlightening editorial, the authors summarized the results of the Nordic-European Initiative on Colorectal Cancer (NordICC) trial and the Screening of Swedish Colons (SCREESCO) trial. The NordICC trial [50] involved nearly 84,585 participants from Poland, Norway, Sweden, and the Netherlands, who were randomly assigned to be invited to undergo either screening colonoscopy or to receive usual care. The risk of CRC decreased by 18% over 10 years (risk ratio, 0.82; 95% CI, 0.70–0.93). However, the reduction in the mortality risk due to CRC remains unsatisfactory. Recently, the results of a modeling study of the NordICC trial were released [51]. With a participation rate of 42% and a 10-year follow-up period, the models projected reductions in CRC incidence ranging from 11% to 28% and in mortality from 24% to 32%. Additionally, they noted that the predicted incidence reduction with a 42% uptake increased from 18% to 33% and from 19% to 35% at the 15- and 20-year follow-ups, respectively. Furthermore, with 100% participation, these reductions rose significantly from 40% to 73% for incidence and from 43% to 77% for mortality. Combining full participation with a 15-year follow-up resulted in anticipated incidence and mortality reductions from 40% to 73% and from 59% to 79%, respectively. Consequently, they recommended a 10-yearly colonoscopy screening interval to achieve the desired reduction in the incidence and mortality.

The SCREESCO trial [52, 53] involved a comparison of 16,552 individuals who underwent colonoscopy every 2 years with those who underwent usual care (no screening). In the preliminary report of this trial, only 35% of the participants invited to undergo colonoscopy actually underwent the procedure. Additionally, endoscopists had a median adenoma detection rate of 20%. Forsberg et al. [52] presented comparative data on the choice between a once-only colonoscopy and a biennial FIT for CRC screening. Among the 30,400 individuals invited to undergo colonoscopy, 10,679 (35%) participated. In the FIT arm, 33,383 of 60,137 individuals (56%) who underwent a mailed FIT test participated. According to the intention-to-screen analysis, 49 participants (1.6 per 1,000) with CRC were included in the colonoscopy arm, as opposed to 121 (2.0 per 1000) in the FIT arm (relative risk, 0.78; 95% CI, 0.56–1.09). The study concluded that population-based screening services could potentially offer benefits in disease-specific mortality if demonstrated subsequently. Strömberg et al. [54] also demonstrated a significant socioeconomic gradient in the attendance proportion for colonoscopy in the primary colonoscopy arm.

Considering these points, we contend that the effectiveness of colonoscopy as an noninvasive colorectal cancer screening test warrants additional scrutiny. In the United States and Europe, where colonoscopies are not as prevalent, the issue extends beyond cost and involves the availability of proficient endoscopists to conduct the procedure and ensure the quality of colonoscopy examinations. The task was to motivate and inform the public effectively to undergo colonoscopy.

In Korea, the situation regarding colonoscopies differs somewhat from that in Western countries. Although colonoscopies are recommended by the National Health Insurance system and are in line with disease-specific guidelines, it is relatively straightforward for patients to undergo colonoscopies based on their own preferences. This is primarily because Korean colonoscopists are highly specialized professionals who have undergone rigorous qualification examinations, which is well-recognized by the public. Consequently, the perceived risk associated with the procedure is low and the cost of colonoscopy is affordable, making it easily accessible. Considering the healthcare landscape in Korea and cost-effectiveness of medical resources, the implementation of a 10-yearly colonoscopy-based CRC screening program is worth considering.

The primary objectives of the NCST are to detect cancer in its early asymptomatic stages, thereby increasing cure rates and ensuring health for individuals. Simultaneously, it aims to mitigate the escalating healthcare costs attributed to advanced cancer cases, safeguard national health by securing a workforce, and promote a healthier society. To achieve these objectives, funding for screening programs is essential, and the availability of sensitive and cost-effective tests is crucial. Above all, the active engagement of the population, due to their conviction of the significance of the screening program, is paramount to its success.

Although the CRC screening rate in Korea has remained relatively stable at 30.5% in 2017, there is scope for improvement. It is worth noting that elective endoscopy rates are presumed to be high in Korea, largely because of the comparatively lower cost of endoscopy as compared to that in Western countries. This will play a pivotal role in evaluating and sustaining the effectiveness of future screening programs. Considering Korea’s swift transition to an ultra-aging society [55], establishing guidelines that efficiently address the medical cost burden associated with the older population is imperative.