Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer patients more accurately than clinical factors

Oncologist. 2015 Feb;20(2):127-33. doi: 10.1634/theoncologist.2014-0325. Epub 2015 Jan 5.

Abstract

Background: Approximately 20% of patients with stage II colorectal cancer will experience a relapse. Current clinical-pathologic stratification factors do not allow clear identification of these high-risk patients. ColoPrint (Agendia, Amsterdam, The Netherlands, http://www.agendia.com) is a gene expression classifier that distinguishes patients with low or high risk of disease relapse.

Methods: ColoPrint was developed using whole-genome expression data and validated in several independent validation cohorts. Stage II patients from these studies were pooled (n = 416), and ColoPrint was compared with clinical risk factors described in the National Comprehensive Cancer Network (NCCN) 2013 Guidelines for Colon Cancer. Median follow-up was 81 months. Most patients (70%) did not receive adjuvant chemotherapy. Risk of relapse (ROR) was defined as survival until first event of recurrence or death from cancer.

Results: In the pooled stage II data set, ColoPrint identified 63% of patients as low risk with a 5-year ROR of 10%, whereas high-risk patients (37%) had a 5-year ROR of 21%, with a hazard ratio (HR) of 2.16 (p = .004). This remained significant in a multivariate model that included number of lymph nodes retrieved and microsatellite instability. In the T3 microsatellite-stable subgroup (n = 301), ColoPrint classified 59% of patients as low risk with a 5-year ROR of 9.9%. High-risk patients (31%) had a 22.4% ROR (HR: 2.41; p = .005). In contrast, the NCCN clinical high-risk factors were unable to distinguish high- and low-risk patients (15% vs. 13% ROR; p = .55).

Conclusion: ColoPrint significantly improved prognostic accuracy independent of microsatellite status or clinical variables, facilitating the identification of patients at higher risk who might be considered for additional treatment.

Keywords: Gene expression signature; Risk classification; Risk prediction; Stage II colon cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Netherlands
  • Prognosis
  • Risk Assessment