Colorectal Cancer Screening in Patients with Inherited Bleeding Disorders: High Cancer Detection Rate in Hemophilia Patients

Introduction: Non-invasive stool tests are the most commonly used colorectal cancer (CRC) screening modalities worldwide. The population-based CRC screening program in the Netherlands uses fecal immunochemical testing (FIT), to detect human hemoglobin in feces, followed by colonoscopy in individuals with a positive FIT. The target population consists of women and men aged 55-75 years. No studies have been conducted on the performance of this screening program in patients with inherited bleeding disorders, such as Von Willebrand disease (VWD) and hemophilia, whereas the FIT performance in these patients may substantially differ from the general population. We hypothesized that the false-positive rate of FIT is higher in patients with inherited bleeding disorders than in the general population. Therefore, our study aims to assess the false-positive rate and positive predictive value of FIT for CRC and advanced adenoma (AA) in patients with VWD or hemophilia.

Methods: We performed a multicenter, nationwide cross-sectional study embedded in two nationwide studies on VWD and hemophilia in the Netherlands, the Willebrand in the Netherlands-Prospective study and the Haemophilia in the Netherlands 6 study, respectively.

Results: In total, 551 patients with inherited bleeding disorders (hemophilia, n=387; VWD, n=164) were included of whom 351 patients participated in the CRC screening program (63.7%). The FIT positivity rate and false-positive rate in hemophilia and VWD patients were significantly higher than in the general population (14.8% vs 4.3%, p<0.001 and 10.3% vs 2.3%, p<0.001, respectively). In hemophilia patients, the detection rate of CRC and/or AA (i.e., the proportion of participants in whom CRC and/or AA was detected) was significantly higher than in the general male population (4.5% vs 1.8% respectively, p=0.012). The positive predictive value of FIT for CRC and/or AA in hemophilia patients was comparable to the general male population (32.3% vs 39.6% respectively, p=0.28). In VWD patients, the positive predictive value of FIT for CRC and/or AA was significantly lower than in the general population (6.3% vs 36.8% respectively, p=0.01). However, the detection rate in VWD patients was similar to the general population (0.8% vs 1.4% respectively, p=0.83).

Conclusion: This study indicates that the false-positive rate of FIT is higher in patients with inherited bleeding disorders than in the general population. Nevertheless, the detection rate of CRC and/or AA in hemophilia patients is high and the positive predictive value of FIT for CRC and/or AA is not affected. In VWD patients, the positive predictive value is lower than in the general population. Therefore, the benefit of the CRC screening program seems different in patients with hemophilia and VWD compared to the general population. Additional studies are needed to evaluate possible adjustment of the CRC screening program for these patients.

Coppens:CSL Behring: Other: Consulting fee, Research Funding; Alexion: Other: Consulting fee; Bayer: Other: Consulting fee, Research Funding; Novo Nordisk: Other: Consulting fee, Research Funding; Daiichi Sankyo: Other: Consulting fee, Research Funding; Roche: Research Funding; UniQure: Research Funding; Sobi: Other: Consulting fee; Viatris: Other: Consulting fee. van der Bom:Bayer: Other: Teaching; Novo Nordisk: Research Funding. Fijnvandraat:Sobi, Sanofi, Novo Nordisk, Roche: Consultancy; EAHAD: Membership on an entity's Board of Directors or advisory committees; CSL Behring, Novo Nordisk, Sobi: Research Funding. Meijer:Alexion: Other: Speaker fee; Octapharma: Other: Participation in data monitoring and endpoint adjudication committee; Bayer: Other: Speaker fee, trial steering committee; CSL Behring: Other: Speaker fee; UniQure: Consultancy. Eikenboom:CSL Behring: Research Funding. Gouw:Sobi: Research Funding. Leebeek:Sobi: Consultancy, Research Funding; uniQure: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding; CSL Behring: Research Funding; Biomarin: Consultancy; Roche: Other: DSMB member for a study. Kruip:Roche: Other: Speakers fee; BMS: Other: Speakers fee; Sobi: Other: Speakers fee, Research Funding.