Abstract and Introduction
Background & Aims Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5−10 times greater compared to the general population, and 25−30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations.
Methods The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February−March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold.
Results The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening at age 30 years within 2 years of the transplantation because of the additional risk for colon cancer associated with immunosuppression.
Conclusions These recommendations aim to help CF adults, families, primary care physicians, gastroenterologists, and CF and transplantation centers address the issue of CRC screening. They differ from guidelines developed for the general population with respect to the recommended age of screening initiation, screening method, preparation, and the interval for repeat screening and surveillance.
Continued therapeutic advances have impressively increased longevity in cystic fibrosis (CF). More than half of the individuals with CF captured in the CF Foundation patient registry are over the age of 18 years. The current median predicted survival is 41 years, and persons born in 2015 have an estimated average life expectancy of 45 years. The increasing longevity of adults with CF puts them at risk for other diseases, such as gastrointestinal cancer.
Recent reports show that individuals with CF have an increased risk of colorectal cancer (CRC) compared to age-matched individuals without CF.[2–5] The rising risk of CRC with age and the increasing lifespan of individuals with CF imply that the number of cases of CRC in this population will climb.
In 2013, Maisonneuve et al published a cohort study based on data from the CF Foundation patient registry covering the years 1990−2009. Based on incidence rates of cancer estimated using data on the general population from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute, this study revealed a standardized incidence ratio of 6.2 for colon cancer (95% confidence interval, 4.2−9.0) in non-transplanted CF persons based on 26 cases. Our literature review disclosed multiple anecdotal published reports (single cases or case series) of CF patients with colon or rectal cancer. All publications found that nearly all CRC develop in persons less than age 50 years, implying that initiating screening at age 50 years, the current recommendation for the average risk non-CF population, may not be appropriate for the CF population. Limited data showed that the majority of tumors arose in the right colon.[6–17]
Only sparse data exist on systematic colonoscopic screening of individuals with CF.[18,19] Colonoscopy screening of CF adults aged 40 years or older at the University of Minnesota found that approximately 25% of individuals had one or more advanced adenomas, as defined by size ≥1 cm and histologic findings. The majority of these individuals had more than 3 adenomatous polyps on their index screening colonoscopy. Furthermore, either rescreening or surveillance colonoscopies at 1- to 3-year intervals continued to show high incidence of adenomatous polyps, including those with advanced features. These results suggest earlier development and accelerated progression of adenomatous polyps in CF.
The mechanisms responsible for increased risk of CRC in CF are unclear. However, the CFTR gene is a tumor suppressor gene in the intestinal tract in mice, where loss of CFTR is associated with intestinal tumor formation.[20,21] CFTR promotes secretion of chloride and bicarbonate, and plays critical roles in epithelial homeostasis in the gastrointestinal tract.[22,23] Decreased level of hydration of the mucus layer likely contributes to bacterial overgrowth at the mucosal surface, which might result in greater tonic stimulation of epithelia.[24–26] Absence of CFTR is associated with dysregulation of the immune response, intestinal stem cells, and growth signaling regulators. Notably, loss of CFTR expression in early stage human CRC in non-CF patients is associated with markedly decreased disease-free survival.
Based on available evidence, the average age of onset of CRC in CF persons is approximately 40 years, or about 20 to 30 years younger than in the non-CF population. Furthermore, when compared to US data from Surveillance, Epidemiology and End Results Program studies, the incidence of CRC in the CF population at age 40−49 years is similar to the incidence of CRC in 65- to 69-year-old persons in the non-CF population.
Recognizing the urgency and importance that the combination of increased life expectancy and a large age-related increased risk of CRC creates, the CF Foundation created a task force to develop CRC screening recommendations for adults with CF, including both the transplant and non-transplant population.
Gastroenterology. 2018;154(3):736-745. © 2018 AGA Institute