April 21, 2023
Colorectal cancer (CRC) is a leading cause of new cancer diagnoses and cancer-associated death. Although CRC is one of the few cancers that can be prevented through screening, roughly a third of individuals who are eligible for screening based on age have not yet undergone screening.
The development of new CRC screening methods may provide an opportunity to individualize screening and increase participation. One of these new modalities is multitarget stool DNA (mt-sDNA) testing, which has been approved for screening individuals who are at average risk of colorectal cancer.
The performance of mt-sDNA testing in patients who have undergone prior radiation therapy (RT) has not been well studied. Because RT can induce gastrointestinal bleeding and alter DNA methylation, some experts have voiced concerns that prior RT may adversely affect the accuracy of mt-sDNA test results, which could lead to false-positive results and unnecessary follow-up colonoscopies.
To address this question, Mayo Clinic researchers conducted a multisite retrospective cohort study that measured the positive predictive value (PPV) of mt-sDNA testing in patients who had undergone RT and compared the results to historical estimates of mt-sDNA test PPV among patients at average risk of CRC. The results of this study were published in Gastro Hep Advances in 2022.
"Our research was inspired by listening to patients," notes Derek W. Ebner, M.D., an advanced gastrointestinal neoplasia fellow at Mayo Clinic's campus in Rochester, Minnesota, and the study's first author. "In patients with a history of radiation therapy for the treatment of cancer, surveillance can include laboratory monitoring as well as cross-sectional imaging, performed as frequently as every few months. In some patients, this type of a protocol can understandably take a toll and limit enthusiasm for other health maintenance principles. Furthermore, radiation can make a colonoscopy more technically challenging. And for some patients, there is increased fear of procedure-associated complications. All of these factors have led patients to ask if they can use a stool-based test for screening."
Study methods
Mayo Clinic researchers retrospectively identified 220 patients seen at academic and community-based practices who underwent RT and subsequent mt-sDNA testing between 2014 and 2016. The follow-up colonoscopy findings from this patient cohort were compared with published reports among patients at average risk of CRC without a history of RT.
Results and conclusions
Overall, the study results demonstrated that prior RT does not appear to adversely affect mt-sDNA test performance.
- Among patients with prior RT, mt-sDNA tests were positive in 45 of 220 patients (20%).
- Colonoscopy findings were available for 42 of the 45 patients with positive mt-sDNA tests, and 31 of the 42 patients (74%) had colorectal neoplasia.
- The PPV of mt-sDNA testing among patients who underwent RT before mt-sDNA test use was similar to the PPV among average-risk patients without prior RT.
"Our results provide the first evidence that the mt-sDNA test performs accurately and can be used confidently among individuals with a history of radiation therapy."
"This research also emphasizes that two-step screening for colorectal cancer is here to stay. Patients have continually showed us that a noninvasive first step, such as the stool-based mt-sDNA test, followed by an invasive second step, colonoscopy, if the first step is positive, leads to the best uptake of colorectal cancer screening. Our results offer a better understanding of the real-world performance of mt-sDNA testing so patients and their providers can make the most informed decisions when considering colorectal cancer screening."
For more information
Ebner DW, et al. High positive predictive value of multitarget stool DNA after aerodigestive tract radiotherapy. Gastro Hep Advances. 2022;1:746.
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