Colorectal Cancer Screening in Individuals Ages 45-49 Years: Point Sensitivity of the Multi-Target Stool DNA Test: 2846

Background Most colorectal cancer (CRC) screening tests have not been rigorously studied in younger age groups. Aims To estimate sensitivity of the multi-target stool DNA (mt-sDNA) test in patients ages 45-49 years. Methods We identified archived stool samples (Exact Sciences; Madison, WI) from individuals ages 45-49 years who had completed an index colonoscopy and had confirmed diagnoses of CRC or advanced precancerous lesions (APL; defined as high-grade dysplasia, >25% villous morphology, or ≥1 cm in size [conventional adenoma or serrated lesion]). Data annotation referent to potential CRC risk factors, other than age, was limited. Stool samples were collected at least 7 days after the index colonoscopy, prior to lesion excision or treatment. Stool samples were processed and analyzed per established laboratory protocols for the mt-sDNA assay. Mt-sDNA test sensitivity for CRC, APL, and CRC+APL was estimated from the available sample set. Samples were collected from 2010-2013 ([NCT01260168][1]) and 2014-2017 ([NCT02503631][2]), with sample testing and analysis in 2019. Results Stool samples were analyzed from 19 eligible subjects, 13 with CRC and 6 with APL. Estimated mt-sDNA test sensitivity for CRC, APL, and CRC+APL were 92%, 83%, and 89%, respectively. Conclusions In this small pilot study using existing archived stool samples from subjects ages 45-49 years, mt-sDNA test sensitivity was similar to previously reported estimates for individuals ages ≥50 years. These results support the application of mt-sDNA screening to 76 average-risk patients beginning at age 45 years. Larger studies are needed to confirm and extend these findings. ### Competing Interest Statement Conflicts of Interest: MD, SS, and EW are employees of Exact Sciences. BMB is a clinical consultant to and equity holder of Exact Sciences. PL serves as Chief Medical Officer for Screening at Exact Sciences through a contracted services agreement with Mayo Clinic. Dr. Limburg and Mayo Clinic have contractual rights to receive royalties through this agreement. ### Funding Statement Financial Disclosures: This study was funded by Exact Sciences (Madison, WI). Other Acknowledgments: Medical writing and editorial support was provided by Rebecca K Swartz, PhD, an employee of Exact Sciences (Madison, WI). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Stool samples were collected from 2010 to 2013 ([NCT01260168][1]) and 2014 to 2017 ([NCT02503631][2]) during studies approved by the Copernicus Group Institutional Review Board. Use of the samples for the current study was covered in the original informed consent. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data are available on reasonable request. Proposals for access to data should be directed to the corresponding author. To gain access, data requestors will need to provide a methodologically sound proposal and sign a data access agreement. Researchers are required to obtain necessary IRB/EC approvals or waivers as applicable to conduct research. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01260168&atom=%2Fmedrxiv%2Fearly%2F2020%2F09%2F03%2F2020.09.01.20177568.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02503631&atom=%2Fmedrxiv%2Fearly%2F2020%2F09%2F03%2F2020.09.01.20177568.atom