Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population.

Bosch LJW1, Melotte V2, Mongera S3, Daenen KLJ2, Coupé VMH4, van Turenhout ST5, Stoop EM6, de Wijkerslooth TR7, Mulder CJJ5, Rausch C1, Kuipers EJ6, Dekker E7, Domanico MJ8, Lidgard GP8, Berger BM8, van Engeland M2, Carvalho B1, Meijer GA1.

Author information

1: Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
2: Department of Pathology, Maastricht University and Maastricht University Medical Center, GROW-School for Oncology and Developmental Biology, Maastricht, the Netherlands.
3: Department of Pathology, Amsterdam UMC-VU University Medical Center, Amsterdam, the Netherlands.
4: Department of Epidemiology and Biostatistics, Amsterdam UMC-VU University Medical Center, Amsterdam, the Netherlands.
5: Department of Gastroenterology and Hepatology, Amsterdam UMC-VU University Medical Center, Amsterdam, the Netherlands.
6: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
7: Department of Gastroenterology and Hepatology, Amsterdam UMC-Academic Medical Center, Amsterdam, the Netherlands.
8: Exact Sciences Corporation, Madison, Wisconsin, USA.

Abstract

INTRODUCTION:

We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics.

METHODS:

Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing.

RESULTS:

The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different.

DISCUSSION:

In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT.