Methods This is a case-control study nested within a trial that tested the effect of type of test and provider on colorectal cancer screening compliance. Non compliant trial subjects were classified as cases, and compliant subjects were classified as controls. We sampled 600 cases and 600 controls matched by their general practitioner, half were invited for screening at the hospital, and the other half directly at their general practitioner's office. Cases and controls answered questions on: distance from test provider, logistical problems, perception of colorectal cancer risk, confidence in screening efficacy, fear of results, presence of colorectal cancer in the family, and gastrointestinal symptoms. Results About 31% of cases never received the letter offering free screening, and 17% of the sampled population had already been screened. The first reported reason for non-compliance was 'lack of time' (30%); the major determinant of compliance was the distance from the test provider: odds ratio 30 minutes vs.
Background The efficacy of colorectal cancer screening (CRCS) using faecal occult blood tests (FOBT) in reducing colorectal cancer (CRC) mortality in the 50–75 year old population has been demonstrated in large randomised trials. The reduction in mortality by screening is strictly linked to its ability to involve as many people among the target population as possible. The scientific literature about the reasons for non compliance has generated few definitive operational recommendations -. Some reviews have summarized the knowledge and indications that have emerged from the literature,. Some studies have identified several factors associated with higher prevalence of FOBT use: presence of symptoms and a family history of CRC are associated with higher prevalence, while the opposite is true for smoking habits. No consistent relation with gender or socio-economic status has been observed.
Other indications come from intervention studies, and the recommendations are consistent: the involvement of one's own physician, phone and mail reminders, and one sample tests all increase compliance. Some prospective studies have found that a previous FOBT was a predictor of compliance, while some studies have found that participation decreased after 75 years of age. Most studies tested a hypothesis based on the Health Belief Model. Finally, several surveys have studied the reasons for non compliance: practical reasons ranked first in most of the studies; not having health problems was also a frequent answer, along with anxiety and embarrassment. The Agency for Public Health of Lazio, Italy, designed a series of studies in order to implement an evidence-based CRCS program; a special focus was given to the barriers to screening, and how to obtain high screening compliance -. In this study we analysed self-reported reasons for non compliance, individual and environmental determinants of screening compliance, and the interaction between them. Study designs.
Jul 14, 2015 Fecal occult blood test (FOBT) is a non invasive, widespread screening method that can reduce CRC-related mortality. Sigmoidoscopy, alone or in addition to FOBT, represents another screening strategy that reduces CRC mortality.
The figure illustrates the design of the three linked studies. The white box represents the reference population; the light grey boxes refer to the survey; the dark grey boxes to the trial; and the shadowed boxes to the case control study. The study design has been described elsewhere; here we summarize the principal characteristics. We selected an opportunity sample of 13 hospitals, out of 20 who will participate in the screening programme in the near future, in order to represent all types of gastroenterology units (5 university hospitals, 2 large research hospitals, 6 local hospitals) and all geographic areas (7 in the metropolitan area of Rome, 2 in the outskirts of Rome, 4 in towns and small cities of the province). From June 2002 to April 2003, all GPs with an office in the 13 hospital districts selected (1192) were surveyed and asked to participate in the randomised trial. In each of the 13 districts, we sampled 10 GPs of the 24.5% (292/1194) who had agreed to participate. The sampled GPs were randomised as follows: in each district, five were assigned to the immunochemical test and five to the Guaiac test (Guaiac Hemo-Fec, Roche Diagnostic, Mannheim Germany, and immunochemical OC-Hemodia, Eiken, Tokio Japan, distributed by Alpha Wasserman, Milan Italy).
We sampled 2/10 of the target practice population for each GP; 1/10 of the GP's beneficiaries were randomised to the GP arm and 1/10 to the hospital arm. The coordinating centre mailed a letter to the population sample: for the half randomised to the GP arm, the letter invited patients to pick up and return the FOBT at the GP's office; for the half randomised to the hospital arm, the letter invited the patient to pick up and return the FOBT at the hospital. The study was submitted and approved by the Committee for Ethics in Screening of the Regional Agency for Public Health, 16th June 2002, approval n° 1.
Informed consent is not required for this type of study. We defined the non-compliant population as cases, and the compliant population as controls. We sampled about 600 cases and 600 controls matched by GP and arm of randomisation. The matched design was imposed to exclude practices with too high or too low compliance because in these extreme situations we had a strong imbalance between cases and controls. We excluded practice populations with compliance lower than 20% and higher than 80% in the GP arm and practice populations with a compliance lower than 10% in the hospital arm (figure ). Questionnaire response rate.
Response to the questionnaire and technical obstacles to screening compliance. The arrows show 12 cases reclassified as controls and 6 controls reclassified as cases during the interview. For the 1200 people sampled we looked for updated telephone numbers and delivered brief telephone questionnaires about the reasons for non-compliance to the cases, and about the reasons for compliance to the controls.
We inquired about distance from the provider, logistical problems, perception of CRC risk, confidence in screening efficacy, fear of the results, family history of CRC, and gastrointestinal symptoms. Analysis Demographic factors, gender, age and residence, were analysed using the entire population participating in the trial, i.e.
All the other information was available only for the sample interviewed. When analysing the trial population, logistic models were constructed taking into account the effect of the GP clusters; when analysing the case control sample, we adjusted for GP and provider. We tested the goodness of fit of the models using the Hosmer and Lemeshow test for deciles of probability. All analyses were performed using Stata 7.0 statistical software. Residence was categorised as follows: Rome, cities with a gastroenterology centre, and cities without a centre.
We also categorized the cities based on the number of inhabitants. We alternated the two in a logistical model and compared the pseudo r squared and the goodness of fit.
The never-reached Figure shows the compliance of cases and controls to the case-control interview. The percentage of people not reachable for the interview was higher among the non compliant than in the compliant group (34.1% vs. The percentage of refusals shows the same group differences but is lower in both groups (2.7% vs. Eighty of the interviewed people who were non-compliant to screening (22.5%) declared not having received any letter inviting them to participate in the programme and they were excluded from the following analysis (figure ). The already-reached Fifty-four non compliant people declared that they had already been screened, 20 by FOBT in the previous two years, 38 by colonoscopy in the previous 10 years and 21 by double contrast barium enema (DCBE) in the previous 10 years (some people had more than one test). They were excluded from the following analysis. On the other hand, we found 82 controls who had already been screened: 11 by FOBT, 60 by colonoscopy, and 28 by DCBE.
These controls were included in the analysis. None of the interviewed people declared to have had a sigmoidoscopy. Analysis of demographics We used the entire population involved in the trial, 7320 individuals, to analyse the effect of most demographic factors.
Women were significantly more compliant, although the size of this effect is small. Compliance increased in men with age until 65–69, and than decreased slightly; among women we did not observe any clear age trend. There was higher compliance outside Rome in medium-sized towns with gastroenterology centres, while people living in small towns and rural areas without centres showed low compliance. Table shows the figures described above and reports the provider effect, i.e. Hospital and GPs, tested in the trial.
Non compliant compliant OR. 95% CI demographics employment status currently employed 69 91 1 homemaker 76 223 2.2 1.3 3.7 retired 53 81 1.1 0.6 1.9 unemployed 2 5 1.8 0.3 9.6 m.i.
27 10 psychological and cultural educational level 0–4 years of study 18 17 1 5–7 years of study 53 119 2.5 1.2 5.2 8–12 years of study 35 83 2.5 1.1 5.6 high school graduate 49 117 2.7 1.3 6.0 university 24 46 2.1 0.9 5.1 m.i. 48 28 Gastrointestinal symptoms no 198 291 1 yes 29 119 2.7 1.7 4.2 CRC cases among relatives No 212 351 1 yes 15 51 1.8 1.0 3.2 logistics lack of time 69 25 0.2 0.1 0.3 distance 1–15 min 122 301 1 15–30 44 75 0.8 0.5 1.3 30 21 15 0.3 0.2 0.7 m.i 40 19 type of transportation public 31 29 1 private 117 218 2.1 1.2 3.7 on foot 67 159 2.1 1.1 4.1 m.i. 12 4 Analysis stratified by provider: in the hospital arm lack of time 32 4 0.04 0.01 0.12 in the GP arm lack of time 37 21 0.3 0.2 0.6. Reasons for non-compliance Only 24 people of the 350 interviewed (6.9%) picked up the test but did not return it, consequently we did not perform separate analyses for initial agreement and actual compliance. Very few people answered the proposed justifications for non-compliance. Table shows the justifications given by the non-compliant, multiple choice answers selected are indicated with a star, and others were summarized from the open answers. The most frequent answer was 'lack of time' (30%), followed by 'feel healthy' (8%) and 'ill during the study' (6%).
Less than ten people chose any of the other answers. About 40% did not respond. Nine people declared to be covered but did not report how or when they were last tested.
Logistical barriers We observed compliance that was three times higher at GP's office than at hospital gastroenterology centres. There was one gastroenterology centre per district, while there were 10 GPs' offices per district. In the case control study we compared the travelling time to the GP office and to the hospital in the two study arms: 84% stated it took less than 15 minutes to reach the GP, 12% reported 15–30 minutes, and 4% 30 minutes, while in the hospital arm, 58% stated less than 15 minutes, 29% 15–30 minutes, and 13% 30 minutes (test for linear trend chi2(df1) = 55.3; P 30 minutes versus. Cultural, psychological and emotional barriers The effect of the educational level was observed for people with fewer than 5 years of education. Anxiety regarding results was reported by 17.8% of the compliant population, fear of the test by 8.8%, and embarrassment by 3.9%. Having gastrointestinal symptoms at the moment of contact is a determinant of compliance: odds ratio 2.7 (95%CI 1.7–4.2).
An effect with borderline statistical significance was also observed for people with a family history of CRC: odds ratio 1.8 (95%CI 1.0–3.2). Limits The response rate for the case control is acceptable, while the participation rate among the GPs is very low and generates several concerns regarding the validity of the overall observed compliance. The difficulty in involving GPs is a well-known problem and can reduce study validity. Nevertheless the comparisons between compliant and non-compliant populations are not affected by the GPs' self-selection; these comparisons are more likely to be biased on the differences in response rates between cases (non-compliant to FOBT) and controls (compliant to FOBT). We did not design this study to be a survey of the Lazio population, although the population sampled for the trial and for the nested case control was a large sample, which was not self-selected.
In designing the study we overestimated the power of the case control. In fact, of 356 non-compliant case interviews, only 227 were informative. Because of the low percentage in the trial of people that picked up the test but did not return it (8.6%), and consequently also in the case control sample (6.9%), we did not perform a separate analysis on initial agreement to participate in screening and actual compliance. We can only affirm that the immunochemical test led to a higher percentage of returned tests than the guaiac test.
The questionnaire may underestimate cultural barriers like fear of the test or anxiety about the results, both due to lack of awareness of the people interviewed, and to the limits of telephone interviews. Never-reached A high proportion of not reached people means the screening programme was inequitable, and due to administrative mistakes denied some their opportunity to be tested. This group can be estimated as the people who did not receive the letter, plus the difference between not contacted cases and not contacted controls.
We estimated that 22% + (34% – 25%) = 31%; about one-third of the non compliant population (about 20% of target population) was not reachable by letter. We had only self-reported information about receiving the letter, and could not verify if in fact the letter had been delivered to the right address and then thrown away. From mammography screening experience, we know that anywhere from 3% to 18% of letters were returned to sender. This was the most relevant barrier we observed for the screening programme, an issue which other researchers have also highlighted -.
Subjects reached This case control study, with the limits described above, is the first survey in our region to explore CRC screening coverage. The proportion of people screened with one of the recommended tests is 15.4% among non compliant and 19.8% among compliant people, and considering that 35% of the general population is compliant, we estimate 17% coverage with an unknown confidence interval. This coverage level is lower than what was found in the USA. The absence of flexosigmoidoscopy in our sample reflects the scarce use of this technique by Italian endoscopists, although some may confuse sigmoidoscopy with colonoscopy. Colonoscopy is the most common test, accounting for 70% of coverage, and consequentially may explain the very low level of coverage.
The screening of high risk groups, such as people with symptoms or with family history of CRC, for whom colonoscopy (or DBCE) is recommended by the guide-lines, represents about one half of the covered population (47.8%). Reported motivations for non-compliance Many people did not provide a motive for non-compliance to screening, and those who did often did not use the answers provided. This may be one of the limits of the questionnaire used: Closed questions with a long list of multiple choices are not well adapted with telephone interviews. Furthermore the proposed answers were based on the Health Belief Model, which does not adapt well to the realities screening non-compliance in our setting. The most common justification was 'lack of time' followed by feeling healthy, two indicators of a low perception of susceptibility, rather than of the severity or of the perception of risks and benefits of the test,. Logistical barriers Our results show that the major determinant of non compliance to CRC screening was the 'lack of time'.
Cultural, psychological and emotional barriers In our study we observed the paradox that fear of the test and anxiety over the results were more frequent in those who took the test than in those who did not. The problem could be with the timing of the interview. We contacted the compliant group after testing, so the questions were connected to something that had already occurred; the non compliant population had to base their answers on a hypothetical situation,. Other reasons for our difficulties in understanding the psychological and cultural barriers may have been the poor fit of the Health Belief Model we used. Other authors have found similar difficulties using this model,. Nevertheless there are indications that cultural and psychological barriers exist: 1) the underestimation of the problem is evident in most of the reasons given by the non compliant, and confirmed by the strong positive effect the presence of symptoms and family history of CRC have on compliance; 2) the anxiety produced by screening, as well as logistical problems of being screened, may be inferred from the high percentage of people who were accompanied to screening; this group surprisingly consisted not only of old women, but also middle-aged men. Authors' contributions PGR was involved in conceiving and designing the study, the statistical analysis and writing the paper.
FB was involved in designing and conducting the study. AF was involved in conceiving and designing the study and writing the paper. SF was involved in designing the study and statistical analyses. PB was involved in conceiving and designing the study and writing the paper. GG was involved in conceiving the study and writing the paper.
All authors read and approved the final manuscript. Towler B, Irwig L, Glasziou P, Kewenter J, Weller D, Silagy C. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, Hemoccult. 1998; 317:559–565.
Box V, Nichols S, Lallemand RC, Pearson P, Vakil PA. Haemoccult compliance rates and reasons for non-compliance. Public Health. 1984; 98:16–25. Doi: 10.1016/S0033-355-4. Farrands PA, Hardcastle JD, Chamberlain J, Moss S. Factors affecting compliance with screening for colorectal cancer.
Community Med. 1984; 6:12–9.
Blalock SJ, DeVellis BM, Sandler RS. Participation in fecal occult blood screening: a critical review. 1987; 16:9–18.
Doi: 10.1016/0091-742-8. Vernon SW. Participation in Colorectal Cancer Screening: a Review.
J Nat Cancer Inst. 1997; 89:1406–1422. Doi: 10.1093/jnci/. Jepson R, Clegg A, Forbes C, Lewis R, Sowden A, Kleijnen J. The determinants of screening uptake and interventions for increasing uptake: a systematic review. Health Technol Assess.
2000; 4:i–vii. Schoen RE. The case for population-based screening for colorectal cancer. Nat Rev Cancer. 2002; 2:65–70. Doi: 10.1038/nrc705.
Rosenstock IM. Patients' compliance with health regimens. 1975; 234:402–403. Doi: 10.1001/jama.234.4.402. Giorgi Rossi P, Federici A, Bartolozzi F, Farchi S, Borgia P, Guastcchi G.
Trying to improve the compliance to colorectal cancer screening: a complex study design for a complex planning question. Cont Clin Trial. 2005; 26:323–330. Doi: 10.1016/j.cct.2005.01.005. Federici A, Giorgi Rossi P, Bartolozzi F, Farchi S, Borgia P, Guastcchi G.
Survey on colorectal cancer screening knowledge, attitudes and practices of general practice physicians in Lazio, Italy. 2005; 41:30–35. Doi: 10.1016/j.ypmed.2004.11.010. Federici A, Giorgi Rossi P, Borgia P, Bartolozzi F, Farchi S, Gausticchi G. The immunochemical faecal occult blood test leads to higher compliance than the guaiac for colorectal cancer screening programs: a cluster randomised controlled trial. J Med Screen. 2005; 12:83–88.
Doi: 10.12053908357. Federici A, Giorgi Rossi P, Bartolozzi F, Farchi S, Borgia P, Guasticchi G. The role of GPs in increasing compliance to colorectal cancer screening: a randomised controlled trial.
Cancer Causes and Control. 2006; 17:45–52. Doi: 10.1007/s10552-005-0380-9. Segnan N, Senore C, Andreoni B, Aste H, Bonelli L, Crosta C, Ferraris R, Gasperoni S, Penna A, Risio M, Rossini FP, Sciallero S, Zappa M, Atkin WS. SCORE Working Group – Italy.
Baseline findings of the Italian multicenter randomized controlled trial of 'once-only sigmoidoscopy' – SCORE. J Natl Cancer Inst. 2002; 94:1763–72. Hosmer DW, Jr, Lemeshow S. Applied Logistic Regression. New York: John Wiley & Sons; 2001. Stata Corporation.
Stata statistical software: release 7.0. CollegeStation, TX. Stata Corporation; 2001. Schoenman JA, Berk ML, Feldmann JJ, Singer A.
Impact of differential response rate on the quality of data collected in the CTS physician survey. Eval Health Prof. 2003; 26:23–42. Doi: 10.11702250077. King J, Fairbrother G, Thompson C, Morris DL. Colorectal cancer screening: optimal compliance with postal faecal occult blood test.
Aust N Z J Surg. 1992; 62:714–9. Ornstein SM, Musham C, Reid A, Jenkins RG, Zemp LD, Garr DR. Barriers to adherence to preventive services reminder letters: the patient's perspective.
1993; 36:195–200. Brunton M, Thomas DR.
Privacy or life: how do women find out about screening mammography services? 2002; 115:U168. Seeff LC, Nadel MR, Klabunde CN, Thompson T, Shapiro JA, Vernon SW, Coates RJ. Patterns and predictors of colorectal cancer test use in theadult U.S.
2004; 100:2093–103. Doi: 10.1002/cncr.20276.
![Fort ross inn Fort ross inn](/uploads/1/2/5/4/125486853/291438137.png)
American Gastroenterological Association Colorectal cancer screening: clinical guidelines and rationale. 1997; 112:594–642. Doi: 10.1053/gast.1997.v112.agast970594. Macrae FA, Hill DJ, St John DJ, Ambikapathy A, Garner JF.
Predicting colon cancer screening behavior from health beliefs. 1984; 13:115–26. Doi: 10.1016/0091-744-6. Spector MH, Applegate WB, Olmstead SJ, DiVasto PV, Skipper B.
Assessment of attitudes toward mass screening for colorectal cancer and polyps. 1981; 10:105–9. Doi: 10.1016/0091-741-6. Bulliard JL, de Landtsheer JP, Levi F. Profile of women not attending in the Swiss Mammography Screening Pilot Programme.
2004; 13:284–9. Doi: 10.1016/j.breast.2004.03.001. Kreher NE, Hickner JM, Ruffin MT, 4th, Lin CS.
Effect of distance and travel time on rural women's compliance with screening mammography: an UPRNet study. Upper Peninsula Research Network. 1995; 40:143–7. Andreu Vaillo Y, Galdon Garrido MJ, Dura Ferrandis E, Carretero Gomez S, Tuells Hernandez J.
Age, health beliefs, and attendance to a mammography screening program in the community of Valencia Rev Esp Salud Publica. 2004; 78:65–82. Nichols S, Koch E, Lallemand RC, Heald RJ, Izzard L, Machin D, Mullee MA. Randomised trial of compliance with screening for colorectal cancer. 1986; 293:107–10.
Abstract The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations.
These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC. NCCN Categories of Evidence and Consensus Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. All recommendations are category 2A unless otherwise noted. Clinical trials: NCCN believes that the best management for any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and second leading cause of cancer death in the United States.
In 2018, an estimated 97,220 new cases of colon cancer and 43,030 new cases of rectal cancer will occur in the United States. During the same year, it is estimated that 50,630 people will die from CRC. CRC risk assessment in persons without a known family history is advisable by age 40 years to determine the appropriate age to initiate screening, although in general, it is currently recommended that screening for persons at average risk for CRC begin at age 50 years.
Individuals at average risk are those aged ≥50 years without personal history of inflammatory bowel disease, adenomas, or CRC; without a family history of CRC or advanced adenomas; and without symptoms such as rectal bleeding. Registry data from the SEER program suggest an increased incidence of CRC in African Americans prior to age 50 years, which led to the recommendation by some in 2005 that CRC screening in African Americans begin earlier, at age 45 years., In addition, epidemiologic reports suggest that the incidence of CRC may be increasing in adults aged.
Screening of average-risk individuals can reduce CRC mortality by detecting cancer at an early, curable stage and may decrease CRC incidence by detecting and removing adenomatous polyps., Currently, patients with localized CRC have a 90% relative 5-year survival rate, whereas rates for those with regional and distant disease are 71% and 14%, respectively, demonstrating that earlier diagnosis can have a large impact on survival. Current technology for CRC screening falls into 2 broad categories: stool/fecal-based tests and structural tests.
In the United States, colonoscopy is the most commonly used CRC screening test for average- and high-risk populations. However, multiple options exist, and the choice of screening modality may also include consideration of patient preference and resource availability.
The updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CRC Screening describe the various screening modalities currently available, as well as recommended screening schedules for patients at average or increased risk of developing CRC. The guidelines are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes or a family history of CRC or advanced adenomas. These NCCN Guidelines Insights review the 2018 updates to the NCCN Guidelines, focusing on CRC screening modalities and schedules.
Stool/Fecal-Based Screening Tests Two types of fecal occult blood tests (FOBTs) are currently available: guaiac-based and immunochemical. More recently, a fecal test to assess for alterations in exfoliated DNA in combination with checking for occult blood has also become available. Abnormal results from any stool/fecal-based screening test are an indication for colonoscopy. The guaiac FOBT is based on the detection of pseudoperoxidase activity of heme in human blood, whereas the fecal immunochemical test (FIT) directly detects human globin within hemoglobin in stool. FIT has been shown to be superior in terms of screening participation rates and detection of CRC. – However, during the meeting to update the 2018 guidelines for CRC screening, the NCCN panel elected to retain guaiac FOBT as a stool-based CRC screening option because regular use been shown to reduce mortality from CRC, – and may remain a reasonable alternative when immunochemical testing is not available.
Guaiac FOBT Direct evidence from randomized controlled trials (RCTs) shows that low-sensitivity guaiac FOBTs reduce mortality from CRC. – In the Minnesota Colon Cancer Control Study, 46,000 participants were randomized to receive guaiac FOBT either annually or biennially or no screening. The study reported that the 13-year cumulative mortality from CRC per 1,000 individuals evaluated was 5.88 and 8.83 in the annual and unscreened groups, respectively; this 33% difference was statistically significant. After 30-year follow-up, a CRC mortality benefit was seen in both the annual and biennial screening groups (annual FOBT: relative risk RR, 0.68; 95% CI, 0.56–0.82; biennial FOBT: RR, 0.78; 95% CI, 0.65–0.93). In addition, long-term follow-up from the Nottingham trial showed that individuals randomized to the biennial guaiac FOBT screening arm had a 13% reduction in CRC mortality at a median follow-up of 19.5 years (95% CI, 3%–22%), despite a 57% participation rate. After adjustment for noncompliance, the reduction in CRC mortality was estimated to be 18%.
This reduction in CRC mortality using low-sensitivity guaiac FOBTs has been confirmed by a systematic review and meta-analysis of multiple studies., The US Preventive Services Task Force (USPSTF) defines the high-sensitivity guaiac FOBT as having a sensitivity for cancer 70% and a specificity 90%. Although high-sensitivity guaiac FOBTs that meet these criteria have not been tested in RCTs, some studies have shown that high-sensitivity guaiac FOBTs have higher CRC detection rates when compared with low-sensitivity guaiac FOBTs. – The NCCN CRC Screening Panel recommends that only high-sensitivity guaiac tests be used.
Fecal Immunochemical Test Unlike guaiac FOBT, FIT does not require dietary restrictions and a single testing sample is sufficient. A meta-analysis of studies that evaluated the diagnostic accuracy of FIT for CRC in average-risk patients found the sensitivity and specificity to be 79% (95% CI, 0.69–0.86) and 94% (95% CI, 0.92–0.95), respectively. Comparative studies have shown that FIT is more sensitive than guaiac FOBT.,– For example, one study demonstrated a higher sensitivity for cancer by FIT compared with a high-sensitivity guaiac FOBT (82% vs 64%). A Dutch randomized study also demonstrated higher detection rates of advanced neoplasia using FIT (2.4%) versus guaiac FOBT (1.1%), although both were less sensitive for advanced neoplasia than flexible sigmoidoscopy (8.0%). In addition, as seen in other trials, FIT had a significantly higher participation rate than guaiac FOBT in this trial. Following extensive literature analysis, an expert panel in Ontario concluded that FIT is superior to guaiac FOBT in both participation rates and detection of advanced adenomas and CRC.
Nonrandomized studies have also shown that FIT screening reduces CRC mortality., In a large Taiwanese population-based study, 1,160,895 individuals aged 50 to 69 years were screened with 1 to 3 rounds of FIT and compared with an unscreened group. With a maximum follow-up of 6 years, a 10% decrease in CRC mortality was seen in the FIT-screened population (RR, 0.90; 95% CI, 0.84–0.95). After reviewing the evidence and considering the potential impact on patient access if guaiac FOBT was removed, the NCCN CRC Screening Panel decided to include a footnote in the 2018 version of the guidelines acknowledging the outlined advantages of FIT over guaiac FOBT, but noting that guaiac FOBT has been shown to decrease mortality from CRC and that high-sensitivity guaiac FOBT can be used as an alternative to FIT (see CSCR-2, page 941). Although an ideal interval for CRC screening with FIT is unclear, data extrapolated from a modeling analysis demonstrated similar life-years gained when annual FOBT strategies were compared with colonoscopy every 10 years.
Currently, the guidelines recommend annual screening intervals using any modality after a negative finding by high-sensitivity guaiac FOBT and FIT. To determine whether this screening interval should be modified, the panel reviewed data from a population-based CRC study of 7,501 Dutch individuals randomly selected to receive 2 one-sample FIT screening rounds with intervals of 1, 2, or 3 years. The total number of advanced neoplasia detected at repeat FIT screening was not impacted by the interval length within the range of 1 to 3 years.
The panel considered potential issues with increasing the interval, including impact on adherence to screening schedules and having discordant recommendations to those of the USPSTF and US Multi-Society Task Force (USMSTF), and decided to leave the recommended annual FIT screening interval unchanged. Future studies may shed light on this issue.
FIT-DNA–Based or Multitarget Stool DNA Test A combined multitarget stool DNA and occult blood test (mt-sDNA) has emerged as an option for CRC screening (Cologuard, Exact Sciences Corp.). It screens for the presence of known DNA alterations ( KRAS mutations, aberrant NDRG4 and BMP3 methylation) during colorectal carcinogenesis in tumor cells sloughed into stool, as well as occult blood as measured by immunoassay. A study that included 9,989 participants at average risk for CRC, each of whom underwent FIT, mt-sDNA testing, and a colonoscopy, found that the mt-sDNA test was more sensitive than FIT for detecting CRC (92.3% vs 73.8%; P=.002), advanced precancerous lesions (42.4% vs 23.8%; P1 cm (42.4% vs 5.1%; P. Colonoscopy Colonoscopy is the most complete screening procedure and is considered the current gold standard for assessing the sensitivity of detecting neoplasia for other screening modalities. The general consensus is that a 10-year interval is appropriate for most average-risk individuals who had a normal, high-quality colonoscopy, defined as an examination complete to the cecum with bowel preparation adequate to detect polyps 5 mm.
Although no RCTs directly demonstrate mortality reduction as a result of colonoscopy, findings from case-control and cohort studies show that colonoscopy and polypectomy have a significant impact on decreasing CRC incidence and mortality. – Interestingly, in a Canadian case-control study that matched each of 10,292 individuals who died of CRC to 5 controls, colonoscopy was associated with lower mortality from distal CRC (adjusted conditional odds ratio OR, 0.33; 95% CI, 0.28–0.39) but not proximal CRC (OR, 0.99; CI, 0.86–1.14). Additional studies have also demonstrated a reduced effectiveness in the right versus left colon., A population-based, case-control study in Germany demonstrated that colonoscopy in the preceding 10 years was associated with an overall 77% decrease in risk for CRC. However, although risk reduction was strongest for distal cancer, a 56% risk reduction was also seen for proximal disease. A case-control study using the SEER-Medicare database also found that colonoscopies are associated with a decrease in death from CRC, and the association was strongest for distal over proximal CRC., Some of these findings of a distal but not proximal risk reduction may be associated with variation in the quality of colonoscopy in alternative settings. Flexible Sigmoidoscopy Evidence from RCTs have also demonstrated that flexible sigmoidoscopy reduces the incidence of and mortality from CRC.,– The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening group reported CRC mortality rates from their RCT of flexible sigmoidoscopy screening, which screened 64,000 participants using this modality, and 59% of those participants a second time at 3 or 5 years. – A 26% reduction in deaths from CRC was seen in the screened group (RR, 0.74; 95% CI, 0.63–0.87; P98,000 participants aged 55 to 64 years.
After 7 years of follow-up, the researchers reported no difference in the incidence of or mortality from CRC between screened and unscreened individuals. However, after 11 years of follow-up, the hazard ratio (HR) for death from CRC was 0.73 (95% CI, 0.56–0.94) in the screened groups.
Interestingly, the addition of FOBT did not affect the long-term outcomes of participants screened with sigmoidoscopy in this trial. The SCORE trial randomized 34,272 individuals aged 55 to 64 years to one-time sigmoidoscopy or no screening and reported incidence and mortality results after 10 years of median follow-up. The intention-to-treat analysis demonstrated a 18% reduction in incidence and a 22% reduction in mortality. In addition, a randomized study examined the effect of flexible sigmoidoscopy offered once between ages 55 and 64 years on CRC incidence and mortality. Compared with the population that did not receive any screening, intention-to-treat analysis showed that intervention with flexible sigmoidoscopy decreased CRC incidence by 23% (HR, 0.77; 95% CI, 0.70–0.84) and CRC mortality by 31% (HR, 0.69; 95% CI, 0.59–0.82). The benefit of one-time sigmoidoscopy demonstrating decreased CRC incidence and mortality was sustained after 17 years of follow-up.
CT Colonography CT colonography (CTC), also known as virtual colonoscopy, is evolving as a promising alternative technique for CRC screening. CTC has the advantages of being noninvasive and not requiring sedation. However, extracolonic findings, which are present in up to 16% of patients, pose a dilemma because they have a potential for both benefit and harm., Data to determine the clinical impact of these incidental findings are currently insufficient, and further investigation is required. The accuracy of CTC in detecting polyps or cancers measuring ≥10 mm has been assessed in several studies, with generally high sensitivity. – In 2005, 2 meta-analyses reviewed the performance of CTC in the detection of colorectal polyps., In one of these studies, CTC showed high average sensitivity (93%) and specificity (97%) for polyps ≥1 cm, both of which decreased to 86% when medium polyps (6–9 mm) were included in the analysis.
In the other meta-analysis, the sensitivity of CTC, although heterogenous, improved as the polyp size increased (48% for polyps 9 mm); specificity was 92% to 97% for the detection of all polyps. Other studies have assessed growth rates of colorectal polyps (6–9 mm) using CTC surveillance, and determined that polyps 6 to 9 mm are unlikely to progress to advanced neoplasia within 3 years. The current NCCN Guidelines for CRC Screening recommend rescreening with CTC in 3 years or colonoscopy if 1 to 2 polyps of 6 to 9 mm are detected. If ≥3 polyps are found or polyps are ≥10 mm, a subsequent colonoscopy is recommended. However, if the CTC screen is negative, the guidelines recommend rescreening with any modality in 5 years. The radiation exposure risk of undergoing a single CTC screening procedure is unknown but likely very low, and no empirical data have shown increased risk at levels below an exposure of 100 mSv. Using the screening protocol for the ACRIN trial, an estimated effective dose of low-dose CTC was projected to be 9 mSv for women and 8 mSv for men, corresponding to 5 radiation-related cancer cases per 10,000 individuals undergoing one scan at age 60 years.
The 2014 American College of Radiology practice guidelines for the performance of CTC in adults recommend the use of a low-dose, nonenhanced CT technique on a multidetector CT scanner to minimize radiation exposure to the patient. Overall, available data indicate that CTC is useful for the detection of larger polyps. Data on optimal frequency, polyp size leading to colonoscopy referral, and protocol for the evaluation of extracolonic lesions are evolving.
Emerging Options: Blood-Based Screening Test The methylation status of the septin9 ( SEPT9) gene has been shown to distinguish CRC tissue from normal surrounding tissue, and circulating methylated SEPT9 DNA in plasma is a biomarker for CRC. – A multicenter study compared the FIT test and a SEPT9 DNA methylated blood test for CRC screening in 102 patients with identified CRC, and found that the sensitivity for CRC detection was not significantly different (68% vs 73.3%, respectively). The PRESEPT study, a prospective multicenter study, assessed the accuracy of circulating methylated SEPT9 DNA at detecting CRC in 7,941 asymptomatic individuals aged ≥50 years who met screening criteria for average risk, and determined the sensitivity and specificity of the methylated SEPT9 DNA blood-based assay to be 48.2% and 91.5%, respectively. An independent clinical performance analysis was conducted on plasma samples from the PRESEPT study using an updated SEPT9 DNA assay and determined that the sensitivity for detecting CRC was 68%, an improvement over the previous report, and the specificity was 80%. Factors that may potentially negatively impact the performance of the SEPT9 DNA test have been suggested, including early-stage disease, age 65 years, diabetes, arteriosclerosis, and arthritis. A blood test that detects circulating methylated SEPT9 DNA is currently FDA-approved and may provide a potential alternative for individuals who refuse other screening modalities.
However, a limitation remains the lack of sensitivity for advanced adenomas. Further, the interval for repeat testing is uncertain. On balance, the NCCN panel felt that there was insufficient evidence to recommend routine use of this assay. Conclusions Clinical decisions regarding recommendations for CRC screening modalities and schedules involve consideration of multiple factors, including age to initiate screening, efficacy, adherence, cost, and patient preference. During the 2018 meeting, the NCCN panel enacted important updates to the NCCN Guidelines for CRC Screening. Based on existing data, the panel agreed that FIT was superior to low-sensitivity guaiac FOBT, but also recognized the wealth of data supporting the benefits of guaiac FOBT in decreasing CRC incidence and mortality.
Emerging data suggest long-term benefit of one-time flexible sigmoidoscopy, but more data are needed to consider screening intervals longer than 10 years. Overall, the availability of multiple screening modalities and evolving screening schedules may offer additional opportunities to decrease CRC incidence and mortality. Footnotes.
Provided content development and/or authorship assistance. Please Note The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines® Insights highlight important changes to the NCCN Guidelines® recommendations from previous versions.
Colored markings in the algorithm show changes and the discussion aims to further the understanding of these changes by summarizing salient portions of the NCCN Guideline Panel discussion, including the literature reviewed. These NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representation or warranties of any kind regarding the content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their applications or use in any way. The full and most current version of these NCCN Guidelines are available at. © National Comprehensive Cancer Network, Inc. 2018, All rights reserved.
The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. Disclosure of Relevant Financial Relationships The NCCN staff listed below discloses no relevant financial relationships: Kerrin M. Rosenthal, MA; Kimberly Callan, MS; Genevieve Emberger Hartzman, MA; Erin Hesler; Kristina M. Gregory, RN, MSN, OCN; Rashmi Kumar, PhD; Karen Kanefield; and Kathy Smith. Individuals Who Provided Content Development and/or Authorship Assistance: Dawn Provenzale, MD, MS, Panel Chair, has disclosed that she has no relevant financial relationships.
Samir Gupta, MD, Panel Vice Chair, has disclosed that he receives grant/research support from Epigenomics AG. Ahnen, MD, Panel Member, has disclosed that serves on the speakers bureau for Ambry Genetics and is on the scientific advisory board for Cancer Prevention Pharmaceuticals.
Markowitz, MD, Panel Member, has disclosed that he has no relevant financial relationships. Chung, MD, Panel Member, has disclosed that he has no relevant financial relationships. Mayer, MD, Panel Member, has disclosed that he has no relevant financial relationships. Regenbogen, MD, Panel Member, has disclosed that he has no relevant financial relationships. Mary Dwyer, MS, CGC, Senior Manager, Guidelines, NCCN, has disclosed that she has no relevant financial relationships. Ndiya Ogba, PhD, Oncology Scientist/Medical Writer, NCCN, has disclosed that she has no relevant financial relationships. This activity is supported by educational grants from AstraZeneca, Celldex Therapeutics, Celgene Corporation, Genentech, Jazz Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, and Seattle Genetics, Inc.
This activity is supported by independent educational grants from AbbVie, Merck & Co., Inc. And NOVOCURE. Copyright © 2018 by the National Comprehensive Cancer Network.