Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study

David A Johnson, Robert L Barclay, Klaus Mergener, Gunter Weiss, Thomas König, Jürgen Beck, Nicholas T Potter, David A Johnson, Robert L Barclay, Klaus Mergener, Gunter Weiss, Thomas König, Jürgen Beck, Nicholas T Potter

Abstract

Background: Screening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population.

Objective: To compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening.

Design: In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy.

Measurements: Plasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively.

Results: For all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9-80.9%) and 68.0% (95% CI 58.2-76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5-86.3%) compared with 97.4% (95% CI 94.1-98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% -95% CI 62.5-80.1%) was shown to be statistically non-inferior to FIT (68.0%-95% CI 58.2-76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%.

Conclusions: At a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC.

Trial registration: ClinicalTrials.gov NCT01580540.

Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: David A. Johnson MD: •Consultant/clinical investigator- Epigenomics. •Advisory Board Given Imaging, CRH Medical, Abbivie, Jansen/Centacor, Takeda, AstraZeneca, Phizer, Medivo •Clinical investigator – EXACT Sciences. Klaus Mergener, MD, PhD, MBA: •Clinical investigator - Epigenomics •Clinical investigator - GI View Ltd •Clinical investigator - CapsoVision •Consultant/clinical investigator - Intromedic •Consultant, Olympus America •Advisory Board - Colon Prep Center •Advisory Board – angelMD. Robert Barclay, MD: •Clinical investigator - Epigenomics. Gunter Weiss: •Epigenomics employee. Thomas König: •Epigenomics employee. Jürgen Beck: •Epigenomics employee at the time of the study. Nicholas Potter, PhD: •Medical Advisory Board – Epigenomics •Clinical investigator- Epigenomics. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. The number of enrolled subjects…
Figure 1. The number of enrolled subjects by class, and the number of blood and stool samples evaluated in the study.

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