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

PLoS One. 2014 Jun 5;9(6):e98238. doi: 10.1371/journal.pone.0098238. eCollection 2014.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Colonoscopy
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology
  • Early Detection of Cancer* / methods
  • Early Detection of Cancer* / standards
  • Female
  • Humans
  • Male
  • Mass Screening / methods
  • Mass Screening / standards
  • Middle Aged
  • Neoplasm Staging
  • Occult Blood*
  • Prospective Studies
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Septins / genetics*

Substances

  • SEPTIN9 protein, human
  • Septins

Associated data

  • ClinicalTrials.gov/NCT01580540

Grant support

The study was sponsored by Epigenomics AG (Berlin, Germany) http://www.epigenomics.com. Epigenomics provided support in the form of salaries for authors GW, TK, JB, and designed this study which was conducted at US clinical sites through an independent clinical research organization (CRO). Results were collated and analyzed consecutively by the sponsor following completion of testing. As per study protocol, manuscript preparation and the decision to publish were overseen by a publication steering committee comprising of DAJ, JB, KM, NTP and RLB. Laboratory testing was performed at an independent US clinical laboratory on all submitted specimens. Eastern VA Medical School, Rockford Gastroenterology Associates, Ltd., Digestive Health Specialists and Molecular Pathology Laboratory Network, Inc., provided support in the form of salaries for authors DAJ, RLB, KM, NTP, respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.