Hadjiliadis D, Khoruts A, Zauber AG, et al. Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations. Gastroenterology. 2018 Feb;154(3):736-745.e14. doi: 10.1053/j.gastro.2017.12.012. Epub 2017 Dec 29.
Purpose and Background
Based on available data from the Cystic Fibrosis Foundation Patient Registry, the median age of onset of colorectal cancer (CRC) in patients with cystic fibrosis is roughly 20-30 years younger than in the general population.
Although colonoscopic data among people with CF remain limited, studies from the United States, Australia, and Canada have consistently shown increased prevalence of pre-cancerous adenomatous colon polyps (precursor growths that have potential to transform into cancer over time), including advanced neoplasia defined by size and/or histopathologic criteria. Furthermore, animal and human studies suggest that altered expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene increases colon cancer risk and may accelerate its progression.
In the general population, mortality from CRC is reduced by screening and early intervention. As most CRC arises from a well-defined adenoma-to-cancer sequence, it is possible to prevent cancer by identifying and removing pre-cancerous polyps during screening colonoscopies.
Given the increased prevalence of adenomatous colonic polyps at a younger age -- as well as the increasing evidence of CFTR mutations as a contributing genetic risk factor -- CF should be considered a genetic adenomatous polyposis and colon cancer syndrome. This distinction is critically important to the future care of aging people with CF.
Immunosuppression associated with organ transplantation (particularly following lung transplantation) has been associated with increased risk for CRC development in CF. Any screening recommendations would need to incorporate specific guidance for people with CF who have undergone solid organ transplantation.
An expert task force composed of 18 members performed a comprehensive literature review, focusing on the following topics: cancer risk, organ transplantation, and procedure and preparation pertaining to CRC screening. The committee held multiple meetings to analyze the available data and synthesize recommendations.
An independent analysis of the benefits and harms of screening, as well as resource requirements, was performed by the Department of Public Health at Erasmus Medical Center, Netherlands. The recommendations also received public comments from the CF community of physicians and patients after being presented at the 2016 North American Cystic Fibrosis Conference.
The final recommendations were included only if they reached 80 percent consensus threshold among the task force members.
|Recommendations||Evaluation of the Evidence|
|1. The CF Foundation recommends that all decisions on colorectal cancer screening and surveillance in individuals with cystic fibrosis be based on shared decisions between the provider and individual with CF about treatment, co-morbidities, safety, and quality of life.||100% Consensus|
|2. The CF Foundation recommends that all colorectal cancer screening and surveillance for individuals with cystic fibrosis are jointly managed by CF health care professionals and an endoscopist.||100% Consensus|
|3. The CF Foundation recommends colonoscopy as the screening examination for colorectal cancer in individuals with cystic fibrosis.||100% Consensus|
|4. The CF Foundation concludes that the evidence is insufficient to recommend the use of CT colonography, stool-based tests, or flexible sigmoidoscopy in individuals with cystic fibrosis for the purpose of colorectal cancer screening.||94% Consensus|
|5. The CF Foundation recommends that colorectal cancer screening begin at age 40 in individuals with cystic fibrosis with continued re-screening every five years.||100% Consensus|
|6. The CF Foundation recommends that individuals with cystic fibrosis who have undergone a colonoscopy that had any adenomatous polyps have surveillance colonoscopy within three years, unless a shorter interval is indicated by individual findings, with subsequent intervals based on the most recent endoscopic examination.||94% Consensus|
|7. The CF Foundation recommends that individuals with cystic fibrosis who are 30 years of age and older and have adequately recovered after receiving a solid organ transplant begin colorectal cancer screening within two years of transplant, except when they have had a negative colonoscopy within the past five years.||100% Consensus|
|8. The CF Foundation recommends continued colorectal cancer re-screening every five years in individuals with cystic fibrosis who have received a solid organ transplant.||100% Consensus|
|9. The CF Foundation recommends that individuals with cystic fibrosis who have undergone a solid organ transplant and had colonoscopy that had any adenomatous polyps have surveillance colonoscopy in three years, unless a shorter interval is indicated by individual findings, with subsequent intervals based on the most recent endoscopic examination.||100% Consensus|
|10. The CF Foundation recommends that adults with cystic fibrosis undergoing a colonoscopy receive intensive regimens for bowel preparation to allow for optimal examination. The intensive regimen should include: 3–4 washes (minimum of 1-liter purgative per wash) with the last wash occurring within 4–6 hours prior to the exam.||100% Consensus|
- Implementation of CRC screening is a new challenge in the care of adults with CF, especially for teams that have not dealt with this problem before. Bowel preparation for colonoscopy must be more rigorous in people with CF because of the physicochemical characteristics of mucus and slower intestinal transit time. Patient education regarding the practical completion and the importance of adequate bowel preparation is critical to the success of all CRC screening programs, and this is especially true for people with CF. Patients and their care teams must partner together to best ensure high-quality performance of colonoscopy.
- The performance characteristics of non-invasive screening tests like the fecal immunochemical test (FIT) are unknown in the CF population. If it is comparable to that in the general population, annual FIT testing may be a reasonable strategy to identify individuals most likely to benefit from colonoscopy. However, this question still needs to be addressed by systematic studies. It is possible that frequent occurrence of multiple polyps in CF patients may increase FIT sensitivity. However, predominance of right-sided neoplasms and slower intestinal transit time in CF may decrease FIT sensitivity. Similarly, specificity of FIT is unknown in CF.
- The mechanisms of CFTR involvement in colon cancer pathogenesis are unknown. Some directions for investigations include the various roles CFTR plays in epithelial homeostasis, altered intestinal microbiota, chronic inflammation, high-fat diet, altered bile acid metabolism, and others. Understanding the underlying mechanisms may lead to development of mitigating medical strategies to decrease the risk for CRC.
- It is unknown whether mutated CFTR heterozygote individuals have an increased risk of colon cancer.
- The consensus recommendations focused exclusively on CRC screening because colon cancer is by far the most common gastrointestinal cancer, and the benefits of CRC screening are well-established in the general population. However, there is also an increased risk of other digestive system cancers and future work will need to address the optimal approaches to deal with this larger challenge. Furthermore, the impact of CFTR modulators on these specific risks of digestive cancer are unknown; further study will be needed to better delineate any impact of risk (either positive or negative).
Relevant manuscripts published after the original guidelines are listed below. These manuscripts have not been reviewed or endorsed by the guidelines committee.
- Gini A, Zauber AG, Cenin DR, et al. Cost-Effectiveness of Screening Individuals with Cystic Fibrosis For Colorectal Cancer. Gastroenterology. 2018 Feb;154(3):556-567.e18. doi: 10.1053/j.gastro.2017.10.036. Epub 2017 Nov 2.
- Abraham JM, Taylor CJ. Cystic Fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer. J Cyst Fibros. 2017 Nov;16 Suppl 2:S40-S49. doi: 10.1016/j.jcf.2017.06.013.
- Hegagi M, Aaron SD, James P, Goel R, Chatterjee A. Increased prevalence of colonic adenomas in patient with cystic fibrosis. J Cyst Fibros. 2017 Nov;16(6):759-762. doi: 10.1016/j.jcf.2017.07.009. Epub 2017 Jul 23.
- Fink AK, Yanik EL, Marshall BC, et al. Cancer risk among lung transplant recipients with cystic fibrosis. J Cyst Fibros. 2017 Jan;16(1):91-97. doi: 10.1016/j.jcf.2016.07.011. Epub 2016 Aug 15.
- Prenner S., Levitsky J. Comprehensive Review on Colorectal Cancer and Transplant. Am J Transplant. 2017 Nov;17(11):2761-2774. doi: 10.1111/ajt.14340. Epub 2017 Oct 4.
Use of These Guidelines
The CF Foundation intends for this executive summary of its guideline to summarize the published guideline. The published guideline summarizes evidence, and provides reasonable clinical recommendations based on that evidence, to clinicians, patients, and other stakeholders. Care decisions regarding individual patients should be made using a combination of these recommendations, the associated benefit-risk assessment of treatment options from the clinical team, the patient's individual and unique circumstances, as well as the goals and preferences of the patients and families that the team serves, as a part of shared decision-making between the patient and clinician.
This executive summary was prepared by:
James M. Abraham, MD, (University of Minnesota) and Alexander Khoruts, MD, (University of Minnesota)
The guidelines were published in February 2018, they were reviewed in July 2021 and it was determined that no update is needed at this time.