Next-generation stool DNA test accurately detects colorectal cancer and large adenomas

Abstract

Background & aims: Technical advances have led to stool DNA (sDNA) tests that might accurately detect neoplasms on both sides of the colorectum. We assessed colorectal neoplasm detection by a next-generation sDNA test and effects of covariates on test performance.

Methods: We performed a blinded, multicenter, case-control study using archived stool samples collected in preservative buffer from 252 patients with colorectal cancer (CRC), 133 with adenomas ≥ 1 cm, and 293 individuals with normal colonoscopy results (controls); two-thirds were randomly assigned to a training set and one-third to a test set. The sDNA test detects 4 methylated genes, a mutant form of KRAS, and the α-actin gene (as a reference value) using quantitative, allele-specific, real-time target and signal amplification; it also quantifies hemoglobin. We used a logistical model to analyze data.

Results: The sDNA test identified 85% of patients with CRC and 54% of patients with adenomas ≥1 cm with 90% specificity. The test had a high rate of detection for all nonmetastatic stages of CRC (aggregate 87% detection rate for CRC stages I-III). Detection rates increased with adenoma size: 54% ≥ 1 cm, 63% >1 cm, 77% >2 cm, 86% >3 cm, and 92% >4 cm (P < .0001). Based on receiver operating characteristic analysis, the rate of CRC detection was slightly greater for the training than the test set (P = .04), whereas the rate of adenoma detection was comparable between sets. Sensitivities for detection of CRC and adenoma did not differ with lesion site.

Conclusions: Early-stage CRC and large adenomas can be detected throughout the colorectum and with high levels of accuracy by the sDNA test. Neoplasm size, but not anatomical site, affected detection rates. Further studies are needed to validate the findings in a larger population and optimize the sDNA test.

Figure 1

Neoplasm detection by next-generation stool DNA test prototypes. ROC curves are shown for (A) training set and (B) test set. See Table 2 for definition of prototype test.

Figure 2

Affect of neoplasm size on stool DNA test detection rates. (A) Adenomas. Detection rates increased directly with lesion size; P < .0001. (B) Colorectal cancer. Although all 8 cancers around 1 cm in size were detected, detection rates overall increased with lesion size; P = .008.

Figure 3

Relationship of neoplasm size to quantitative stool DNA test scores: colorectal adenoma vs cancer. When stool DNA test scores were plotted against neoplasm size by piece-wise linear regression, curves for adenomas and cancers did not differ significantly; P = .40.

Figure 4

Effect of neoplasm site on detection rates by stool DNA testing. Detection rates were comparable between proximal and distal colorectal cancers (P = NS) and between proximal and distal adenomas (P = NS).

Figure 5

Affect of colorectal cancer stage on detection rates by stool DNA testing. Detection rates did not differ significantly between stages I, II, or III. However, aggregate sensitivity of 87% for stages I–III was significantly higher than the sensitivity of 69% for stage IV; P = .02.