A multi-center study of non-invasive colorectal cancer evaluation in cystic fibrosis (NICE-CF)

Background People with Cystic Fibrosis (PwCF) have a higher risk of digestive cancers compared to non-CF age-matched cohorts. Colonoscopy is the standard for colorectal cancer (CRC) and precancerous lesion screening. In the general population stool-based testing provides a non-invasive option for CRC screening. We evaluated performance and feasibility of stool-based testing for CRC screening in PwCF. Methods This was a cross-sectional multi-center study comparing stool-based testing (multi-target DNA-based test/Cologuard™ (mt-sDNA) and quantitative FIT test) to colonoscopy for CRC screening in PwCF. NPV and sensitivity of stool-based testing to detect non-advanced precancerous polyps and advanced neoplasia (CRC or advanced precancerous lesions) in PwCF were calculated. Results 362 participants enrolled at 26 US centers. 254 with analyzable mt-sDNA and/or FIT test completed colonoscopy (70% of enrolled). Mean age was 47 years; 50% were female. The majority were Caucasian; 78% reported CFTR modulator use. Prevalence of non-advanced precancerous polyps and advanced neoplasia was 46%. Participants age ≥ 40 had similar rates to < 40 (46% vs. 42%), as did males and females (48% vs. 43%). FIT in PwCF for non-advanced precancerous polyps and advanced neoplasia had NPV of 0.55 (0.48–0.61), PPV of 0.61 (0.39–0.80), and low sensitivity of 0.11. FIT for advanced neoplasia alone had improved NPV but low sensitivity and PPV. Mt-sDNA in PwCF with non-advanced precancerous polyps and advanced neoplasia had NPV of 0.58 (0.51, 0.64), PPV of 0.59 (0.45- 0.72), and low sensitivity of 0.27. Mt-sDNA for advanced neoplasia alone also demonstrated improved NPV but low PPV and low sensitivity. Conclusion FIT and mt-sDNA testing demonstrate low NPV and sensitivity in the high-risk CF population; these tests cannot be recommended as alternatives to colonoscopy for CRC screening for PwCF. ClinicalTrials.gov