Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations

Denis Hadjiliadis; Alexander Khoruts; Ann G. Zauber; Sarah E. Hempstead; Patrick Maisonneuve; Albert B. Lowenfels


Gastroenterology. 2018;154(3):736-745. 

In This Article

Discussion and Areas for Future Research

Raising Awareness of Colorectal Cancer Risk and Acceptability of Screening

Because of the absence of any information on other screening procedures, the task force recommends colonoscopy screening as the current best screening procedure. Thus, a key issue is acceptability of this procedure by the CF community. One member of the task force contacted several CF care centers and found a high degree of compliance when colonoscopy was recommended, with level of patient education on bowel preparations being a key factor for acceptance. Because many patients and center directors appear to be unaware of the increased risk of CRC in CF patients, an educational component will be required to increase compliance with the listed recommendations.

Importance of Other Potential Risk Factors

There are many other risk factors within the CF population for which there is insufficient evidence to determine the impact on overall CRC risk. These factors include family history of CRC, sex, age of CF diagnosis, presence or absence of meconium ileus, diabetes, distal intestinal obstruction syndrome, and pancreas function status. Further information will be required to determine the potential importance of all these potential modifying factors.

With respect to mutational status, a recent cohort study found patients with severe genotypes had a somewhat higher risk of CRC than patients with milder mutations.[3] However, milder mutations are present in a small minority of patients with CF (<10%) and therefore too few data exist to make any different recommendations for that group at this time. In any case, such patients have longer survival, thus possibly longer time to develop CRC. In an Australian screening study,[9] all 4 CRCs and 1 ileal tumor developed in CF persons who were Delta F508 homozygotes. However, additional studies must be conducted to determine the cancer risk in older patients with milder CF mutations.

Role of Fecal Immunochemical Test Testing and Other Screening Modalities

The task force did not recommend FIT testing, but the modeling results suggest that screening with FIT, assuming that the method is both sensitive and specific, may be even more cost-effective in individuals with CF than screening with colonoscopy.[30]

Considering both screening modalities, the model found that the optimal screening strategy for non-transplant CF patients is annual FIT from age 35 to 75 years. This strategy was both more effective (46 vs 44 LYG) and less costly ($2.5 vs $2.6 million) than the optimal colonoscopy strategy. For post-transplantation patients with CF, the optimal strategy of annual FIT was slightly less effective than the optimal colonoscopy strategy (54 vs 56 LYG), but the task force decided the incremental resources required for the colonoscopy strategy ($1.3 million with colonoscopy vs $1.0 million for FIT) was acceptable.

Although FIT screening remained the optimal strategy in most sensitivity analyses, evidence for the performance of FIT in CF patients is currently lacking. The model findings of performance of FIT should therefore be confirmed in clinical studies before recommendations for FIT screening can be made in CF patients. Important information about the suitability of FIT testing and other screening modalities in the CF population could be obtained from a study combining and comparing synchronous screening using the testing modality and colonoscopy screening. Another test of potential value would be a stool-based test for tumor DNA. Although noninvasive procedures would have several potential advantages, any positive test would require a confirmatory colonoscopy.

Comparison of Modeling Results and Task Force Recommendations

The recommendations of the task force were consistent with the model recommended strategies for non-transplant CF patients to begin colonoscopy screening at age 40 years with repeat colonoscopy every 5 years assuming negative screenings. The modeling provided insights into how to balance the LYG with screening to the burden of screening for non-transplant and transplant CF patients.[30] The model considered age to begin screening, intervals of repeat screening, and surveillance intervals for those with adenomas or cancers. For non-transplant patients, screening beginning at age 40 years with 5-year interval provided the best balance between LYG and burden of screening for the non-transplant subjects with incremental cost-effectiveness ratios below the commonly used threshold of $100,000. For transplant patients, Microsimulation Screening Analysis modeling suggested starting colonoscopy screening at age 35 years, given that transplant had occurred at age 30 years if the incremental cost-effectiveness ratio level of $100,000 was used. If transplant occurred before age 30 years, the model suggested that patients should receive colonoscopy starting at age 30 years. The task force elected to also recommend colonoscopy screening fairly soon after recovery from transplantation for patients transplanted at age 30 years to increase the efficacy of transplantation itself (Figure 2).

Generally, modeling strategies consider age to begin and age to end screening; however, we did not designate an age to end screening for individuals with CF because there were few differences in effectiveness by end age. (See modeling paper and its appendices).[30] As with the non-CF population, a prudent approach would be to stop screening in adults with CF who have less than a 10-year life expectancy.

Discussion of Special Considerations In The Transplant Population

All data on organ transplants relate to lung transplant, as it accounts for >90% of transplantation procedures in CF patients. In addition, no data exist on liver transplant recipients (second most common), and occasional other solid organ transplants for individuals with CF. Liver transplant recipients use lower immunosuppression and likely have lower CRC risk; however, they have improved survival and thus a longer time to develop CRC.[42] Based on this, the recommendations are for all solid organ transplant recipients with CF[1,43] (As of September 30th, 2016, 5039 organ transplants have been performed for CF: 4622 lung transplants, 358 liver transplants, and 59 heart-lung transplants; Re-transplant patients should follow the same recommendations as first transplants.

Careful evaluation of the patient's CRC risk and survival likelihood should be taken into account each time point that screening is considered. In cases where expected survival is limited (ie, <10 years), screening should not be performed. For adults appropriately selected, lung transplantation usually increases survival probability. Therefore, a lung transplantation candidate with a short life expectancy is likely to become a screening candidate before and after transplantation at the appropriate ages described here because the potential survival then increases to approximately 10 years.[32,38]

A particularly difficult situation will arise in patients with severe disease who cannot undergo screening before lung transplantation. In this case, careful consideration should be given to factors like age, risk factors, and risk of colonoscopy. The CF and lung transplantation team should discuss any other screening options acknowledging their limitations, including the option of delaying screening until after lung transplantation.

Discussion About Colonoscopy: Preparation Details, Poor Preparation Repeat Procedures, Right-Side Lesions, and Rapid Regrowth

A high-quality bowel preparation is essential for optimal detection of colon polyps.[44–46] The physicochemical characteristics of stool and intestinal mucus complicate bowel preparation. A number of Food and Drug Administration−approved preparations exist, but given the increased-intensity regimens needed in CF patients, different preparations need to be tested for results and patient acceptability. In addition, non-Food and Drug Administration−approved preparations, such as over-the-counter polyethylene glycol combined with sport drinks, are commonly used in the general population.[47–49] These have the advantage of greater patient tolerability and may have a role in CF patients, but careful attention needs to be paid to potential electrolyte shifts if such preparations are intensified in volume.[50]

Surveillance and Rescreening

At this time, we recommend a 3-year surveillance interval for those with adenomas detected and a 5-year rescreening interval for adults with CF who have prior negative findings. This ensures simplicity for implementation and following of the recommendations. Decisions should always be based on last colonoscopy. As more data become available, it is possible that different subpopulations will need more or less frequent schedules for rescreening and surveillance. Our recommendations are making an effort to balance the risk of missing advanced CRC and minimizing the burden and risk of too frequent examinations.

Prevention of Cancer in the Cystic Fibrosis Population

At present, screening appears to offer the best way to lower the risk of developing CRC in CF persons. Lifestyle modification by avoiding known CRC risk factors, such as smoking and obesity are unlikely to be effective because these factors are usually absent in individuals with CF. There is the possibility that chemopreventive agents, such as cyclooxygenase inhibitors (eg, aspirin) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) could be helpful.[51] Finally, CFTR modulators, which increase the expression of the CFTR protein, might also decrease the likelihood of CRC.