|Year : 2019 | Volume
| Issue : 2 | Page : 42-55
Colorectal cancer screening guidelines for Nigeria in 2019
Olusegun Isaac Alatise1, Olalekan Olasehinde1, Abdulfatai Bamidele Olokoba2, Babatunde M Duduyemi3, Olusola C Famurewa4, Oludare F Adeyemi5, Elugwaraonu A Agbakwuru1, AW Asombang6
1 Department of Surgery, Obafemi Awolowo University, Ile-Ife, Nigeria
2 Department of Medicine, University of Ilorin, Ilorin, Nigeria
3 Department of Pathology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
4 Department of Radiology, Obafemi Awolowo University, Ile-Ife, Nigeria
5 Department of Radiotherapy, University of Benin, Benin, Nigeria
6 Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
|Date of Submission||16-Sep-2016|
|Date of Decision||10-Dec-2019|
|Date of Acceptance||17-Mar-2020|
|Date of Web Publication||22-May-2020|
Prof. Olusegun Isaac Alatise
Department of Surgery, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538, Ile-Ife
Source of Support: None, Conflict of Interest: None
Colorectal cancer (CRC) is a major public health issue in Nigeria. The incidence is rising, and majority of the patients diagnosed with CRC, die of the disease burden. CRC is an ideal cancer for screening and early detection. It has been well documented that screening for CRC, by a variety of methods, leads to a sustained reduction in mortality from the disease in two ways: increased detection of early stage with more curable cancer and detection and removal of adenomas, which are known precursors to CRC. Screening has also been shown to be cost-effective in terms of quality-adjusted life-years gained compared to nonscreening. CRC screening can be approached as an organized program or on an opportunistic basis. Opportunistic screening is the only option in systems that lack the resources, infrastructure, and framework needed for an organized approach. A myriad of CRC screening tests exist, which can be divided into two main categories namely biological sample-based tests, which include fecal, blood, and urine tests, and colonic structure-based tests, which include flexible sigmoidoscopy, colonoscopy, and imaging studies such as computed tomography colonography, magnetic resonance imaging colonography, and double-contrast barium enema. The recommendation for CRC screening includes offering patients the opportunity to select test, based on their preference, affordability, and test availability. This decision-making process is personalized and requires an understanding between the patient and doctor. This guideline reviews the available evidence and makes recommendation on the screening method for CRC in Nigeria.
Keywords: Colonoscopy, colorectal cancer, fecal immunochemical test, Nigeria, screening
|How to cite this article:|
Alatise OI, Olasehinde O, Olokoba AB, Duduyemi BM, Famurewa OC, Adeyemi OF, Agbakwuru EA, Asombang A W. Colorectal cancer screening guidelines for Nigeria in 2019. Niger J Gastroenterol Hepatol 2019;11:42-55
|How to cite this URL:|
Alatise OI, Olasehinde O, Olokoba AB, Duduyemi BM, Famurewa OC, Adeyemi OF, Agbakwuru EA, Asombang A W. Colorectal cancer screening guidelines for Nigeria in 2019. Niger J Gastroenterol Hepatol [serial online] 2019 [cited 2020 Jun 5];11:42-55. Available from: http://www.njghonweb.org/text.asp?2019/11/2/42/284715
| Colorectal Cancer in Nigeria: Disease Burden, Outcomes, and Potential Solutions|| |
Colorectal cancer (CRC) is the most common gastrointestinal (GI) cancer in Nigeria and the third most commonly diagnosed cancer globally, after lung and breast cancers.,, In addition, CRC is the fourth most common cause of cancer-related mortality worldwide, with a lifetime incidence in average-risk individuals of approximately 5%. In low- and middle-income countries (LMICs), the incidence of CRC is projected to increase by 70% by 2030. This has significant implications for Nigeria's nascent cancer care system, where CRC was previously believed to be rare. Recent evidence suggests a dramatic rise in the incidence of CRC in Nigeria – the world's most populous African country – with a 5-fold increase from 1979 to 2008. A review of the Nigerian cancer registry data confirms a growing burden of CRC, which now ranks as the fourth most common cancer in Nigeria.,
The GLOBOCAN database suggests that most patients with CRC in LMICs will die of the disease. A comparative review of CRC outcomes from a tertiary care hospital in Nigeria and a specialized cancer center in the United States (MSKCC), demonstrated that stage for stage, Nigerian CRC patients fared statistically significantly worse (Stage III, Nigeria 62% vs. MSKCC 88%, P < 0.01; Stage IV, Nigeria 10% vs. MSKCC 45%, P < 0.01). A prospective analysis of 400 patients from an institutional cancer registry showed that only half of the Nigerian CRC patients survived beyond 1 year; the 5-year survival was significantly worse compared to the outcomes reported in both high-income countries (HIC) and middle-income countries (e.g., India).
Various factors are responsible for the poor outcomes observed in CRC patients in Nigeria. These include poor health-seeking behavior (i.e., awareness of common symptoms); lack of standardized preoperative, surgical, and postoperative care; high out-of-pocket payments due to poor health insurance coverage; failure to adhere to prescribed treatments of chemotherapy and radiotherapy (in many instances secondary to cost); and lack of standardized screening guidelines (i.e., for opportunistic and organized screening) that would facilitate early detection. Currently, concerted efforts are being made to tackle many of these problems. One such effort includes the launching of the National Cancer Control Plan 2018–2023 by the Federal Ministry of Health in collaboration with numerous public and private stakeholders. This document identifies CRC prevention through screening and early detection as a national priority. This builds on an increase in diagnostic and therapeutic infrastructure, including the increased accessibility of endoscopy in both public and private facilities across the country., Recent evidence from some of these institutions has suggested that colorectal neoplasia in West Africans is more common than previously documented.,
The country has also witnessed an upsurge in the number of cancer-related nongovernment organizations, which have been actively involved in public education via both electronic and print media.,, This may account for a portion of the increased CRC incidence, through greater case detection secondary to improved public awareness, but longer life expectancy and an increasingly Western diet and lifestyle are felt to be significant contributors. Indeed, the modifiable or unique CRC risk profile in Nigeria has not be well studied and is an area of inquiry ripe for prospective evaluation. Regardless, the growing burden of CRC and the poor outcomes associated with late-stage disease, require a focused effort to improve early detection. Locally relevant CRC screening guidelines are a fundamental building block of any national effort to improve early detection.
| Colorectal Cancer Screening: Overview|| |
Screening is the identification of unrecognized disease in an asymptomatic individual by means of tests, examinations, or other procedures that can be applied to a target population. The goal of screening is to detect disease before it is symptomatic. Screening for a given disease is feasible when the condition is common and treatable and has an identifiable preclinical phase. CRC fulfills these criteria and is therefore a preventable cancer. Screening can be discussed as being either opportunistic or organized. Opportunistic screening is initiated on a case-by-case basis by either the patient or by a health-care professional. Organized screening is a complex, multifaceted process that involves many components of the health-care system. It can be either population based or targeted in scope and seeks to preemptively enroll eligible individuals.
CRC screening is the process of detecting early-stage CRCs and precancerous lesions in asymptomatic people with no prior history of cancer or CRC neoplasia. The treatable premalignant stage in the development of CRC, adenomatous or serrated polyps, represents the outcome of the first molecular changes required for the development of invasive cancer. In a longitudinal series including most of the HICs, adenomatous or serrated polyps take approximately 10 years to acquire the additional genomic alterations to become cancer. This makes CRC an ideal target for early detection and prevention through screening.
Screening differs from surveillance. Surveillance refers to the recurrent use of tests, examinations, or other procedures in patients with previously detected disease or precancerous lesions. Screening is also distinct from diagnostic tests or examinations, which refer to the investigation of patients with symptoms or positive screening tests other than colonoscopy. Colonoscopy is generally the test of choice for diagnostic examination of patients with GI symptoms such as rectal bleeding.
| Types and Effectiveness of Screening|| |
Once a patient is diagnosed with CRC, survival is dependent on stage at diagnosis and access to timely and safe surgical and medical intervention. Surgery is one of the most cost-effective interventions for treating cancer and offers the only chance for cure in many disease states. Surgery is most effective when CRC is diagnosed early. Screening is the only intervention that can lower the stage of CRC at presentation and possibly reduce its occurrence.
It has been well documented that screening for CRC, by a variety of methods, leads to a sustained reduction in mortality. Screening has also been shown to be cost-effective in terms of quality-adjusted life-years gained compared to nonscreening. Moreover, recent evidence suggests that CRC screening may now be cost-effective in LMICs.,,,
CRC screening can be approached as an organized program or on an opportunistic basis. The International Agency for Research on Cancer defines an organized screening program as one that has the following features: (1) an explicit policy with specified age categories, method, and interval for screening; (2) a defined target population; (3) a management team responsible for implementation; (4) a health-care team for decisions and care; (5) a quality assurance structure; and (6) a method for identifying cancer occurrence in the population. In contrast, opportunistic screening takes the advantage of patients' clinical/hospital visit to engage in screening protocols. It also provides the chance to identify individuals at high risk for CRC. Compared with opportunistic screening, organized screening incorporates a number of additional domains, such as health promotion and quality assurance., When well executed, organized screening can reduce overscreening and identify poor quality service delivery (e.g., identify providers with high complication rate)., Organized screening typically involves a single screening instrument that is followed by diagnostic evaluation if positive.
In the setting of opportunistic screening, health-care providers can use several different tools. Typically, the screening tools and frequency are set out in national guidelines. Physicians are free to pick the screening instrument that best suits the patients' risk tolerance, CRC risk profile, comorbidities, and financial means (i.e., in the absence of effective insurance). Opportunistic screening may be the most feasible and cost-effective option in systems that lack the resources, infrastructure, and framework needed for an organized approach. Opportunistic screening as the dominant strategy is uncommon in well-developed health-care systems, but frameworks have been developed to ensure the effectiveness of this strategy. For instance, almost 60% of the Americans report participating in some form of CRC screening, despite the absence of an organized program. This is secondary to generous reimbursement for colonoscopy and significant public awareness.
| Colorectal Cancer Screening Test Options|| |
A myriad of CRC screening tests exist, which can be divided into two main categories: (1) biological sample-based tests, including fecal, blood, and urine tests, and (2) colonic structure-based tests, which include flexible sigmoidoscopy (FS), colonoscopy, computed tomography (CT) colonography, magnetic resonance imaging (MRI) colonography, and double-contrast barium enema. Each strategy has differing characteristics with respect to accuracy, invasiveness, interval, costs, and quality of evidence supporting its use. An overview of the advantages and disadvantages of each is summarized in [Table 1].
|Table 1: Common screening tests for colorectal cancer: Advantages and drawbacks|
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Stool-based tests include guaiac-based fecal occult blood test (gFOBT), as well as the fecal immunochemical test (FIT) and the newer stool DNA test. Traditionally, stool-based testing has been used to stratify patients that will undergo colonoscopy.
Guaiac-based fecal occult blood test
As CRCs or polyps increase in size, they may bleed. Bleeding can be occult (i.e., not visible) and may be intermittent. gFOBT identifies the presence of heme in stool and hence, may detect occult bleeding from a CRC or polyp. In this test, stool is placed on a guaiac-impregnated paper; in the presence of heme, a peroxidase reaction occurs, causing the paper to turn blue. This is a qualitative assessment, which means the test is interpreted by the user as negative or positive. Patients who are positive are subsequently referred for a diagnostic investigation, usually colonoscopy. To account for the potentially intermittent nature of CRC bleeding, stool sampling is usually required from at least three separate stool samples. The test is also not specific to human blood: any heme present in the stool sample can interact with the guaiac, including nonhuman heme, such as ingested red meat, poultry, and fish, as well as some raw fruits and vegetables such as melons, Telfairia occidentalis (Ugu), water leaf, banana, Okra, turnips, and horseradish. A false-negative result can also occur with intake of Vitamin C supplements or high levels of foods containing Vitamin C. Thus, it has been recommended to refrain from ingesting all these items for 3–5 days prior to testing. Withdrawal of nonsteroidal anti-inflammatory drugs, including aspirin, has also been advocated for 7 days to reduce (but not prevent) nonspecific bleeding., Dietary modifications may reduce the false-positive rate, but this is at the expense of reduced participation due to the added complexity. gFOBT is also nondiscriminatory in terms of the site of bleeding. Upper GI bleeding will also give a positive result.
Testing can be performed on rehydrated or nonrehydrated samples. Rehydrated gFOBT is more sensitive at the expense of decreased specificity. gFOBT is also limited by its poor sensitivity for the detection of adenomas and CRC, compared to other screening modalities. The relatively low sensitivity of gFOBT is countered by its low cost and ready availability. It has also been well studied in large randomized controlled trials (RCT) that show a clear reduction in CRC incidence and mortality with regular use in asymptomatic individuals.,,,,, Tests can be sent through mail directly to patients. Samples are collected at home and can be returned by mail to a central processing laboratory. Depending on the specific frequency (biannual vs. annual) and procedure (e.g., rehydrated), gFOBT is associated with a 15%–33% reduction in CRC mortality[,,,,, and a 17%–20% reduction in CRC incidence., Several different iterations of gFOBT now exist, and most organized screening guidelines recommend a high-sensitivity product.
Fecal immunochemical test
FIT analyzes stool samples for the presence of blood using a mono- or polyclonal antibody to human globin. When human globin is present, it forms a complex with the antibody, which can be quantified., FIT has several advantages over gFOBT. Unlike gFOBT, it is not affected by false-positive results from food, as it is specific for human globin, and it only requires one stool sample. In addition, because the globin protein is rapidly degraded by upper GI enzymes, blood from the upper GI tract is not detected by FIT, making it more specific for bleeding of colorectal origin. A meta-analysis of FIT accuracy demonstrated that its overall pooled sensitivity for CRC detection is 0.79 (95% confidence interval [CI], 0.69–0.86), with a specificity of 0.94 (95% CI, 0.92–0.95)., It also has a relatively high sensitivity for advanced adenomas (approximately 30%), and the advanced adenoma yield over two rounds of screening did not differ if more than one sample was taken at each screening round. This suggests that single sample testing is adequate., In many countries, annual FIT is the stool-based screening test of choice due to its high sensitivity for detecting CRC and advanced adenomas.,,, FIT also has better participation than colonoscopy when used for screening in an average-risk population. Patient compliance and satisfaction with FIT have been shown to be greater than that with gFOBT. Participation in organized screening may be 12% higher with FIT over gFOBT, even when dietary restrictions for gFOBT are removed., One major disadvantage of FIT is the poor sensitivity and specificity for sessile serrated polyp (SSP) detection.
Another significant advantage of FIT over gFOBT is the ability to control the cutoff level for a positive result. This is possible with both qualitative and quantitative tests. A quantitative FIT removes subjective interpretation; the processing and interpretation of a quantitative FIT product is automated. The cutoff threshold for a positive result has a significant impact on the performance of the test. As the cutoff threshold increases, the positive predictive value and specificity increase at the expense of sensitivity. Three commonly used cutoff thresholds are 20, 50, and 100 μg/g (100, 250, and 400 ng/mL, respectively)., This ability to vary the “positive test”Z; cutoff allows screening programs to tailor the test performance to available resources, such as endoscopy capacity. This is particularly important in LMICs where endoscopy capacity is limited but growing.
There is a relationship between ambient temperature and FIT positivity because globin degrades at a rate that is both time and temperature dependent., It has been demonstrated that FIT positivity decreases during the hotter months in countries with year-round, population-based screening. However, the impact on overall test performance remains unclear. A Korean study did not find a significant relationship between high ambient temperature exposure and neoplasia detection despite a drop in test positivity, and a French study reported no correlation between FIT positivity rate and the season of FIT testing. A large retrospective study of 199,654 quantitative FITs from a population-based screening program in Italy, demonstrated a 17% lower probability of a positive result in the summer compared with tests performed in the winter. This resulted in a lower rate of advanced adenoma and CRC detection during the warmer months. Doubeni et al. also showed a significant seasonal variation in FIT performance, characterized by lower sensitivity in hotter months. There may also be a difference in temperature-dependent performance between products. To introduce FIT into a setting like Nigeria with a high, year-round ambient temperature and possibly longer processing times, these issues are particularly salient and will need to be monitored and investigated closely as stool-based screening becomes more common.
Stool DNA test
Like other cancers, CRC is rooted in genomic alteration that regulates cell growth and survival. Mutations that contribute to CRC pathogenesis are either inherited (i.e., germ line mutations) or acquired (i.e., somatic mutations). Genomic alteration can also occur through nongenetic mechanisms, such as epigenetic methylation. CRC develops through one of the following three pathways: chromosomal instability; microsatellite instability (MSI); or the CpG island methylator phenotype pathway., While there is overlap between the pathways, they each have a distinct phenotype. Searching for markers of neoplasia in stool is based on studies showing that tumor cells and DNA are shed into the colonic lumen where they combine with the fecal material. Specific genes can be isolated from stool that are consistent with a neoplasm somewhere in the GI tract. During the early part of the previous decade, investigators examined several different mutations for their presence in the stool of persons with colorectal neoplasia. Early stool DNA tests detected only one marker, but newer tests detect multiple targets and have demonstrated higher sensitivity than FIT for advanced adenoma (42% vs. 23%) and CRC (92% vs. 72%) detection. However, this improved sensitivity comes at the expense of higher test positivity (16% vs. 7%, for FIT) and would therefore place a greater demand on endoscopic resources.
Stool DNA testing has been approved for screening in combination with FIT, and it has been suggested that a 3-year screening frequency is appropriate. The FIT assay tested in a recent study examining a stool DNA test plus FIT demonstrated a 73.8% sensitivity for cancer. This suggests that most of the CRC sensitivity of a dual FIT-fecal DNA test can be achieved without the addition of DNA markers. Advantages of the FIT-fecal DNA test include the highest single-time testing sensitivity for cancer of any noninvasive, nonimaging CRC screening test. In addition, the study demonstrated a 40% sensitivity for SSP >1 cm in size. In the same study, the sensitivity of FIT for SSPs was equal to the false-positive rate.
The major disadvantage of the FIT-fecal DNA test is the substantial decrease in specificity (e.g., 89.8%) compared with 96% for the FIT test alone and high cost relative to FIT. Specificity decreased with increasing age and was only 83% in persons aged >65 years. The cost of the FIT-fecal DNA test is approximately $600 for privately insured patients and about $500 for Medicare patients in the US – about ten times the direct costs of annual FIT. Moreover, there is a further increase in relative costs related to higher numbers of colonoscopies per test. There is currently no information regarding the programmatic sensitivity of the FIT-fecal DNA test.,,, Given these findings, the FIT-fecal DNA test is unlikely to replace FIT in large organized screening programs in the near-to-medium term. The FIT-fecal DNA test may be appropriate for patients, 50- to 65-years' age group, who are seeking a noninvasive test with very high sensitivity for cancer., Available evidence suggests that asymptomatic patients with a positive FIT-fecal DNA test and a negative high-quality colonoscopy do not need the colonoscopy repeated or evaluation of the remainder of the GI tract.
Colon structure-based tests
Colon structure- and image-based tests include FS, colonoscopy, CT and MRI colonography, and double-contrast barium enema.
FS screens for adenomas and other premalignant lesions using a flexible endoscope inserted into the distal colon. The aim is to examine at least the rectum and sigmoid and if possible, as far as the splenic flexure. This procedure may be very relevant in Nigeria as about 70% of the CRC are located on the left side. FS is associated with lower costs, a shorter learning curve, and a more limited bowel preparation than colonoscopy. It can often be done with little or no sedation in an office setting. For these reasons, FS capacity would be easier to scale up in Nigeria relative to colonoscopy. The disadvantages of FS include a lower benefit in protection against right-sided colon cancer compared with the level of protection achieved in case–control and cohort studies using colonoscopy. It should be noted that 25% of polyps in Nigerian patients are located on the right side. In addition, the absence of sedation leads to lower participant satisfaction compared to a fully sedated colonoscopy.
There have been four RCTs of FS-based screening in individuals 55–74 years of age. A pooled analysis of these studies estimated a risk reduction of 18% for CRC incidence and 28% for deaths from CRC as well as reduction in distal colon and rectosigmoid cancer incidence and mortality of 29%–76%, respectively.,, Further, a more recent pooled analysis of three of these four studies evaluated the effect of age and gender on CRC incidence and mortality, demonstrating a reduction of 24% and 33%, respectively, in men regardless of age, but a smaller effect in women, and in women younger than 60 years. Compared to gFOBt or FIT, FS has a higher detection rate for advanced neoplasia (i.e., advanced adenomas and CRC), but has a lower specificity and sensitivity than colonoscopy for both advanced adenomas and CRC.
FS screening for average-risk individuals is often recommended at 5-year intervals. However, there is no clear reason why FS should not be recommended at 10-year intervals, like the recommendation for colonoscopy. Some guidelines actually recommend a 10-yearly interval in combination with yearly FIT.
Colonoscopy with polypectomy results in a 76%–90% reduction in the incidence of colon cancer in appropriately screened individuals. The advantages of colonoscopy include high sensitivity for cancer and all classes of precancerous lesions, single-session diagnosis and treatment, and long intervals between examinations (e.g., 10 years) in patients with normal examinations. One or two negative examinations may signal lifetime protection against CRC. Although colonoscopy is considered the gold standard test in the prevention of CRC as it allows direct assessment of the entire colonic mucosa, its operator dependent nature, variations in physician performance, and other technical issues limit its effectiveness, especially for right-sided neoplasia. A postcolonoscopy CRC (a CRC diagnosed within 3 years of negative colonoscopy) suggests that a cancer or premalignant polyp may have been missed at colonoscopy. A nationwide review demonstrated that this occurred at a rate of 8.6%, and this should be considered when counseling participants. In view of this, quality measures have been introduced to assess the quality of colonoscopy. These measures include adenoma detection rate (ADR), cecal intubation rate, and withdrawal time. The postcolonoscopy CRC rate is an important indicator of the quality of colonoscopy, and it has been demonstrated that endoscopists with higher ADR have lower post colonoscopy CRC rates.,,, As such, ADR is used as a key surrogate marker for quality. In order to realize the benefits of screening with colonoscopy, serial practice audits should be regularly carried out and should inform accreditation of any endoscopy center.
Disadvantages of colonoscopy include the need for a thorough bowel preparation, a higher risk of perforation relative to the other screening tests, higher risk of aspiration pneumonitis (particularly when the procedure is performed with deep sedation), a small risk of splenic injury requiring splenectomy, and a greater risk of postprocedural bleeding compared with other screening tests. A meta-analysis of population-based studies found risks of perforation, bleeding, and death of 0.5/1000, 2.6/1000, and 2.9/100,000, respectively., Bleeding after colonoscopy is almost entirely related to polypectomy. The risk of post-polypectomy bleeding is related to polyp burden, size, and proximal colon location. Cold resection techniques are effective and can be used for nonpedunculated lesions <1 cm in size. Despite these risks, colonoscopy is the preferred approach to the management of any benign colorectal polyp regardless of size or location because the alternative is surgical resection, which has a higher mortality and cost compared with colonoscopy. To the extent that other screening tests effectively identify large lesions, they result in colonoscopy and do not prevent adverse events related to colonoscopic resection of large lesions.
Colonoscopy is occasionally offered as the initial screening tool of choice in countries where screening is offered opportunistically and also for high-risk patients. Two large-scale RCTs are underway to explore the outcomes of population-based colonoscopy screening, but no results are expected until the next decade. Cohort studies of patients undergoing colonoscopy have estimated cancer mortality to be 68%–88% lower among persons who undergo screening colonoscopy than among those who do not. A meta-analysis of observational studies showed that despite a 68% lower mortality overall, no significant mortality benefit from colonoscopy was seen with respect to cancer in the proximal.,
Computed tomography colonography
CT colonography has replaced double-contrast barium enema as the test of choice for colorectal imaging for nearly all indications. CT colonography is more effective than barium enema and better tolerated, hence barium enemas are consequently no longer considered appropriate for screening., In addition, CT colonography can be used in patients with failed colonoscopy, for evaluation of the colon proximal with an obstructing lesion and for CRC screening in patients who refuse or who have contraindications to colonoscopy.
Advantages of CT colonography include a lower risk of perforation compared with colonoscopy and sensitivity of 82%–92% for adenomas ≥1 cm in size., It can also help to detect extra colonic lesions of various significance, leading to further evaluation, which can eventually increase the cost of screening., Disadvantages of CT colonography include the use of bowel preparation. CT colonography can be performed with laxative-free protocols, but this results in clear reductions in sensitivity relative to colonoscopy, including for large polyps. The sensitivity of CT colonography for polyps <1 cm is less than that of colonoscopy, and detection of flat and serrated lesions is the major deficiency of CT colonography.,, Detection of extracolonic findings by CT colonography is common, and these findings have been classified by the American College of Radiology according to their clinical relevance., Radiation exposure is generally viewed as a disadvantage of CT colonography. Although studies have shown that the benefits of screening CT colonography outweigh the radiation risk, avoiding radiation altogether may be the best option because the effective dose accumulates with repeated examinations. Evidence that CT colonography reduces CRC incidence or mortality is lacking. Even in centers where CT colonography has long been available, the impact of CT colonography is limited. Primary care physicians view the need for frequent follow-up examinations and management of incidental extracolonic findings as major factors limiting the utility of CT colonography.
Magnetic resonance colonography
Magnetic resonance colonography (MRC), which was initially used in 1997, may be a valuable method for CRC screening, as it is safe and does not have ionizing radiation like CT colonography., Researchers report that quite promising results have been obtained with MRC. CT colonography has several advantages over MRC, including reduced examination time, fewer imaging artifacts, higher voxel resolution, wider availability, less operator dependency, and lower cost. However, a major advantage of MRC over CT colonography is the lack of ionizing radiation, a potential limitation of screening CT colonography. If patients are aware of radiation risks and are given a choice between MRC and CT colonography, they may opt for the former.
Another major disadvantage of MRC is cost, which is a deterrent to its widespread use. In addition, MRC like CT colonography can potentially help detect extracolonic findings, which may require further investigation. This leads to additional cost and patient anxiety. To date, no research has been carried out on the cost incurred by patients who undergo further evaluation of an incidental finding detected at MRC. It should be noted that MRC is not indicated in individuals with claustrophobia, metallic implants, or cardiac pacemakers. Bowel preparation is also required as in CTC.
| Emerging Technologies not Currently Recommended for Routine Screening|| |
Methylated Septin 9 DNA
This is a blood test to detect circulating methylated Septin 9 DNA (mSept9), a molecular CRC biomarker shed by the tumor into the circulation, as a test for average-risk individuals who have repeatedly refused other forms of CRC screening., Because patients with a positive mSept9 test should be referred for colonoscopy, they must be prepared to undergo a follow-up test that they previously had rejected for screening. Most studies of mSept9 have been tandem studies comparing advanced neoplasia detection rates with a conventional CRC screening test. In one prospective study, mSept9 demonstrated a sensitivity and specificity of 48% and 91%, respectively, for detecting CRC in an average-risk population scheduled to undergo colonoscopy. mSept9 has superior sensitivity compared to gFOBT, especially for CRC at early stages., Since introduction, the test has been modified repeatedly. The most recent products have a sensitivity for cancer and advanced adenomas of 73%, with a specificity of 82%.
Although these studies demonstrate improving test sensitivity, concerns remain about poor specificity compared with recommended screening options and the limited base of evidence in asymptomatic, screening populations. In addition, there has been no microsimulation modeling of the newer version of the test to estimate its benefit, a benefit–harm ratio, or a screening interval for regular testing, which also has not been established by the manufacturer. An accurate blood test would have obvious value in the repertoire of screening options, and even a test with somewhat poorer performance would likely contribute in adults persistently nonadherent to screening recommendations. In both instances, adherence would likely be high. However, based on the limitations noted above, at this time, mSept9 is not included in most guideline as an option for routine CRC screening for average-risk adults.
Early versions of capsule endoscopy principally were used to evaluate the small bowel, but interest has grown in the past decade to apply this technology to CRC screening. The device incorporates a camera on both sides of an ingestible capsule that captures images of the colon and rectum as it passes through the GI tract. The images are recorded and stored in an external device worn by the patient and later analyzed by a clinician. The test is complete when the capsule is passed in the stool.,
In a systematic review of the diagnostic accuracy and safety of capsule endoscopy for the detection of colorectal polyps (i.e., <6 mm) in persons with signs or symptoms of CRC or at high risk for the disease, the reported pooled sensitivity and specificity of capsule endoscopy were 87% (95% CI, 77%–93%) and 76% (95% CI, 60%–87%), respectively., The results showed improved test performance for larger polyps (i.e., ≥10 mm), with pooled sensitivity of 89% (95% CI, 77%–95%) and specificity of 91% (95% CI, 86%–95%).,, Adverse events associated with capsule endoscopy were reported in <4% of patients, which mostly included nausea, vomiting, abdominal pain, and fatigue from the required bowel preparation. Capsule retention is the most serious reported problem and occurred in 0.8% of patients (95% CI, 0.2%–2.4%). Like other endoscopic procedures, capsule endoscopy requires adequate cleansing of the colon and if polyps are found, a colonoscopy may be needed to further investigate and remove precancerous polyps. At this time, capsule endoscopy has not been approved for CRC screening.
Recent efforts have suggested that urine can be screened for CRC. The first urine-based screening test produced is PolypDx™ with a high accuracy for detection of cancer, precancerous, adenomatous polyps. In a Canadian-based clinical trial of 1000 patients, PolypDx™ demonstrated significantly higher accuracy than current fecal-based screening test to detect adenomatous polyps. Recent review has looked at various biomarkers in urine that can be used for screening of CRC.
Once screened, patients with a positive result and presenting a risk of adenomatous polyps can be directed to a colonoscopy during which the adenomatous polyps can be removed, thus preventing the progression into CRC. Those patients with negative results can continue with regular repeated screening with PolypDx™.
In addition, urine metabolomic markers can also be used to monitor response to treatment and recurrence of disease.,
| Choice of Screening Tests|| |
The recommendation for CRC screening includes offering patients the opportunity to select either a structural (visual) examination or a high-sensitivity stool-based test, depending on patient preference and test availability. Each screening option differs in the extent of patient burden and in ways that can affect a patient's choice of test and subsequent adherence, including screening frequency, screening location (home vs. medical facility), need for dietary and/or bowel preparation, need for sedation, time and transportation required, relative ability to prevent versus detect CRC, out-of-pocket cost, risk of complications, and test accuracy. There is evidence that patients will have a preference for one type of screening test over others if provided sufficient information regarding these test attributes, although no single test appears to consistently dominate patient preferences, supporting a strategy of offering choice.,,,, Intention to screen is also higher if the screening test ordered is consonant with the patient's preference., Decision aids that help patients choose among options have been shown to improve knowledge and interest in screening and lead to increased screening compared with not providing information. Trials offering a choice between a stool test and a structural examination compared with either test alone have generally demonstrated greater uptake when a choice is offered.
| Feasibility of Colorectal Cancer Screening Methods in Low- and Middle-Income Countries|| |
Utilizing the population-based average-risk screening strategies recommended in HIC countries in Nigeria would be very challenging for several reasons. First, early effectiveness data show that organized screening strategies cannot be financially justified. However, the premise for these analyses is debatable. Generalization of cost-effectiveness analyses from one country to another is imprudent, due to differences in screening costs, resource capacity, and population preferences. Second, the health-care resources available for screening in Nigeria, like most other African countries, are so limited that an organized strategy could easily overwhelm the system. Third, the challenges in following up patients who screen positive, in addition to uncertainty regarding the distribution, analysis, and reimbursement of tests provided by the government, are greater than that in HICs. Fourth, there is difficulty in identifying the population to screen. The recommended screening strategy for a setting like Nigeria should be opportunistic screening. However, for opportunistic screening to be successful in Nigeria, two important mechanisms must be deployed which include inclusion of various screening modalities into the national insurance scheme to provide coverage and massive structured public and provider enlightenment. The Ministry of Health and nongovernmental organizations (NGOs) should be in the forefront of such educational programs. In addition, attention should be paid to identify possible barriers and facilitators for CRC in Nigeria. This knowledge will help to develop appropriate educational materials that can be used.
| Identifying the Population to Screen|| |
Screening becomes more effective if the appropriate population to screen is identified. Most medical societies in HICs start screening for average-risk population from the age of 50 years. The median age of occurrence of CRC is about 50 years in Nigeria. Because it takes about a decade for polyps to become cancerous, the age of starting screening for an average-risk individual must be lower in Nigeria than in countries like the USA, where age of occurrence is generally higher. Generally, CRC screening is recommended to start from age 40 in Nigeria.
In view of the number needed to screen vis-a-vis available resources, we must be innovative in the organization and introduction of a screening strategy for CRC in Nigeria. One approach could be to introduce screening only to high-risk individuals. This group would include individuals with a family history of CRC and those with early symptomatic disease.
CRC has been described as one of the most hereditary cancers, with about 30% of all CRCs being described as familial. Familial CRC can be classified as either syndromic (with well-described highly penetrant germline mutations such as Lynch and polyposis syndromes) or nonsyndromic. Nonsyndromic CRC accounts for about 25% of all familial CRC. First-degree relatives have 2–3 times the risk of developing advanced adenomas and cancer than the general population if their relatives develop CRC after the age of 50 years. This risk increases as the relative's age at diagnosis decreases and the number of relatives with CRC increases., Therefore, timely screening of first-degree relatives is an important tool in decreasing the rates of CRC, especially among younger people who constitute the bulk of CRC cases seen in Nigeria. Studies have justified the cost-effectiveness of this model of screening in other settings.,,, For example, a group in South Africa has shown that both CRC-related and overall survival are better when colonoscopy screening is offered to a high-risk population with identified genetic mutations for CRC in the Northern Cape Province., While this method of screening family members of those with specific mutations is novel, it is difficult to replicate in most developing countries like Nigeria where the genetic laboratories in which such mutations can be routinely detected are lacking. Because previous reports have documented the high risk of CRC in families with CRC, we suggest the possibility of using this model to select individuals for screening.
Genetic mutation analysis is important in some patients with CRC. There is generally no consensus on who should have genetic mutation screening following the occurrence of CRC. The reason for genetic analysis is to detect patients with syndromic CRC who will need risk reduction measures to prevent the occurrence of other cancers. The only measure that guarantees detection of all syndromic CRC is to screen all CRC patients for MSI with immunohistochemistry or mismatch repair genes. While this is now routine in some cancer centers in developed countries, sustainability of such a screening model is difficult in economically challenged countries. Some guidelines recommend MSI screening only for patients with CRC who are younger than 70 years. This measure has been shown to perform better than the Revised Bethesda Guidelines for testing CRC for MSI in terms of missing rate for syndromic CRC. Nevertheless, in 10%–15% of sporadic CRC cases, MSI and loss of expression of MLH1 are due to hypermethylation of the MLH1 gene promoter.,,, These sporadic cases are also frequently associated with the somatic BRAF V600E mutation. Therefore, if loss of MLH1/PMS2 expression is observed, analysis of somatic BRAF V600E mutation should be performed first. If BRAF V600E is negative, the patient should proceed to have mutation analysis.
Beyond familial or genetic-based screening, symptom-based screening has already been validated in a multicentric, prospective, cross-sectional trial in Southwestern Nigeria. In 362 patients with self-reported rectal bleeding, the incidence of CRC was 18.2%. When a symptom-based risk model was generated using questionnaire data from the first 217 patients, 89% of CRC was predicted in a subsequent validation cohort of 145 symptomatic individuals. CRC was associated with the combination of change of bowel habits, weight loss, and at least 1 week of rectal bleeding with an odds ratio of 12.8. Over 70% of those individuals identified with invasive disease had early-stage, resectable cancer, which marks a dramatic downstaging for a CRC cohort in Nigeria. In Nigeria, where there are significant resource limitations, minimal endoscopy capacity, and heterogeneous CRC incidence, a targeted approach to organized CRC screening is an appropriate starting point. Highly targeted, symptom-based screening with colonoscopy could be considered, while the building blocks for a program of broader, albeit still targeted, asymptomatic screening are put in place. In time, targeted stool-based screening of asymptomatic individuals with a family history of CRC could be piloted through tertiary care facilities with both functional endoscopy units and prospective cancer registries (i.e., those registries being used to identify high-risk families for enrollment).
| Recommendations|| |
- All adults aged 40 years and above with symptoms of rectal bleeding, change in bowel habit, and weight loss should be offered a test to evaluate the colon and rectum
- Individuals with a family history of CRC should have opportunistic screening tests starting about 10 years or so from the age of 40 years (i.e., around the age of 30 years)
- The average population should have CRC screening tests at the age of 40 years and above. This should be advised by the attending doctor any time such patients present in the hospital or clinic for any disease condition
- We recommend that all patients younger than 50 years of age and who are positive based on the revised Bethesda guideline should have MSI test performed
| Screening Test and Interval for Average-Risk Individual|| |
[Figure 1] and [Figure 2] show the recommended screening tests and frequency. Our suggestion for the frequency of screening is as follows:
- Biennial screening with FIT (in the absence of FIT, we suggest high-sensitivity gFOBT)
- Screening for every 5 years with FS and annual screening with FIT (in the absence of FIT, we suggest high-sensitivity gFOBT)
- Screening for every 10 years with colonoscopy
- Screening for every 5 years with CT colonography.
There is an urgent need for a feasibility study to assess the impact of the above recommendation on the health system and mortality from CRC in Nigeria.
| Organized Outreach|| |
To be able to achieve the set goal, it will be necessary to organize outreach to the target population. This should be done in partnership with NGOs interested in CRC. Interestingly, there are many of such NGO that have started launching CRC screening on a small scale. This outreach should target one geopolitical region at a time so as to reduce the logistical issues that arise when conducting large-scale, population-based outreach.
| Quality Assurance|| |
The overall quality of any CRC screening program depends on the quality of the entire screening process. All aspects of the screening must be validated. Laboratory personnel and equipment must be monitored for variation, and quality control standards must be used. Nomenclatures must be defined and uniform across all sites. For example, distal CRC is defined as affecting the rectum, sigmoid colon, and descending colon. Proximal CRC includes the splenic flexure, transverse colon, hepatic flexure, and ascending colon. It should be noted that ADRs in Nigeria are lower than that reported in the West. Hence, quality measures for colonoscopy in Nigeria must consider Nigeria's unique disease landscape. Further study is needed to validate the ideal quality measures for colonoscopy in Nigeria.
| Conclusion|| |
CRC screening via an opportunistic approach of asymptomatic average-risk patients aged 40 years and above using sequential biennial FIT and endoscopic method is feasible in Nigeria and may help reduce the morbidity and mortality associated with CRC. Similar method should be recommended to high-risk patients with alarming symptoms or with a family history of CRC. All efforts should be made by all stakeholders to mobilize every resources and opportunity needed to encourage screening for CRC in Nigeria.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]