Beyond the Scope: Improving Colorectal Cancer Screening With Stool DNA Testing

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

As an oncology nurse practitioner, my daily work underscores the inherent limitations of cancer screening tests. Many patients grapple with types of cancer lacking effective screening, while others face cancer diagnoses at an age younger than the recommended starting point for screening. Even when patients undergo screening, tests are not flawless and may overlook certain cancers or pre-cancerous lesions. Recognizing these challenges, ongoing efforts to improve cancer screening are imperative.

The American Cancer Society recommends colorectal cancer (CRC) screening for adults aged 45 years and older at average risk, utilizing high-sensitivity stool-based tests (fecal immunochemical test, high-sensitivity guaiac-based fecal occult blood test, or multitarget stool DNA test) or structural examinations (colonoscopy, CT colonography, or flexible sigmoidoscopy). Positive results on non-colonoscopy screening tests necessitate follow-up with a colonoscopy.¹

Despite these recommendations, CRC screening, particularly via colonoscopy, often triggers reluctance among patients due to its invasive nature. The procedure involves inserting a flexible tube into the rectum, and the preparatory fasting and colon cleansing can be burdensome. This apprehension acts as a significant barrier to routine screening, potentially causing individuals to delay or avoid this crucial examination.

In my role, I frequently advise patients on the benefits of colonoscopy for CRC screening, as it not only detects cancer but can also prevent its development by removing pre-cancerous lesions. However, the challenges associated with this test may lead some patients to seek less invasive alternatives. Therefore, the potential for a less intrusive test to detect pre-cancerous lesions represents a significant paradigm shift in the approach to screening for patients.

Comparing Tests

Most colorectal cancer screening programs around the world rely on fecal immunochemical testing (FIT), which detects hemoglobin in the stool. However, in the United States, colonoscopy is the most common screening modality. The multitarget immunochemical test (mtFIT) detects hemoglobin and incorporates additional tests to identify the DNA of cells shed by advanced adenomas or CRC.²

While a mtFIT known as Cologuard received FDA approval in the United States in 2014, this test is not considered as cost-effective as FIT or colonoscopy, and it is not currently marketed outside of the United States.²

Wisse et al. recently conducted a comparison between the use of mtFIT and FIT in a population-based colorectal cancer screening program in Holland. The study enrolled individuals aged 55-75 years who were eligible for the Dutch national FIT-based colorectal cancer screening program. Patients submitted both a FIT and mtFIT sample collected from the same stool specimen. A positive FIT or mtFIT result led to a colonoscopy referral. The primary outcome of the study was the detection rate of all advanced neoplasia.³

A total of 15,283 patients consented for the study, and 13,187 patients provided both mtFIT and FIT samples with valid results. Of these, 1404 patients (10.6%) tested positive with either FIT or mtFIT, or both, and were offered colonoscopy. Complete data were available for 1270 of those patients (90.5%). Among them, 335 patients were found to have advanced neoplasia, resulting in a detection rate of 2.54%. This included 29 patients (8.7%) with colorectal cancer, 241 patients (71.9%) with advanced adenoma, and 65 patients (19.4%) with advanced serrated polyps.

Of the 13,187 participants, 1201 patients tested positive with mtFIT (positivity rate of 9.11% [95% CI, 8.62%-9.61%]), while 538 individuals tested positive with FIT (positivity rate of 4.08% [95% CI, 3.75%-4.43%]).

Advanced neoplasia was identified in 299 patients who tested positive for mtFIT, yielding a detection rate of 2.27% (95% CI, 2.02%–2.54%), and in 159 patients with a positive FIT result, resulting in a detection rate of 1.21% (1.03%–1.41%). When compared to FIT, mtFIT exhibited a higher capability in detecting colorectal cancers (26 with a detection rate of 0.20%; 95% CI 0.13%–0.29% vs 23 with a rate of 0.17%; 0.11%–0.27%), advanced adenomas (216 with a detection rate of 1.64%; 1.43%–1.87% vs 114 with a rate of 0.86%; 0.72%–1.04%), and advanced serrated polyps (57 with a detection rate of 0.43%; 0.33%–0.56% vs 22 with a rate of 0.17%; 0.11%–0.26%).

Nursing Considerations

The results from the above study indicate that mtFIT surpasses FIT in its efficacy for identifying advanced adenomas, suggesting its potential to decrease colorectal cancer incidence in a population-based screening program. The study also showed that the adoption of mtFIT screening proved to be cost effective.³

While I will continue to recommend colonoscopies to willing patients, these advancements in non-invasive testing reinforce my commitment to providing informed and patient-centric recommendations, balancing efficacy and patient comfort. The integration of less invasive yet effective screening options like mtFIT holds significant promise, especially in countries where colonoscopy availability may not be as widespread as it is in the United States.

References

1. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281. doi:10.3322/caac.21457
2. Shaukat A, Levin TR. Current and future colorectal cancer screening strategies. Nat Rev Gastroenterol Hepatol. 2022;19(8):521-531. doi:10.1038/s41575-022-00612-y
3. Wisse PHA, de Klaver W, van Wifferen F, et al. The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes: a Dutch population-based, paired-design, intervention study. Lancet Oncol. 2024;25(3):326-337. doi:10.1016/S1470-2045(23)00651-4