Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study

Contemp Clin Trials. 2019 Sep;84:105820. doi: 10.1016/j.cct.2019.105820. Epub 2019 Aug 7.


Background: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES.

Purpose: To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT).

Methods: The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year.

Results: Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1 month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09).

Conclusion: Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP.

Keywords: Clinical exome sequencing; Comparative effectiveness; Hereditary colorectal cancer/polyposis.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / diagnosis
  • Adenomatous Polyposis Coli / genetics
  • Aged
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Communication
  • Comparative Effectiveness Research
  • Confidentiality
  • Cost-Benefit Analysis
  • Exome
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Health Resources / statistics & numerical data*
  • Health Services / statistics & numerical data*
  • Humans
  • Male
  • Middle Aged
  • Research Design
  • Sequence Analysis, DNA
  • Socioeconomic Factors