Home >> ALL ISSUES >> 2019 Issues >> AMP case report: FDA-approved DNA blood test for colorectal cancer prompts patient to undergo colonoscopy

AMP case report: FDA-approved DNA blood test for colorectal cancer prompts patient to undergo colonoscopy

image_pdfCreate PDF

CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Epigenomics. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

Nicholas Potter, PhD
Faisal Bhinder, MD
Jeffrey Cossman, MD

March 2019—Colorectal cancer is the third most diagnosed cancer and the second highest cause of cancer mortality in men and women, and in 2016 it accounted for about nine percent of all diagnosed cancers in the United States.1 When CRC is detected at an early localized stage, the five-year survival rate is 90 percent. With progression to regional disease, five-year survival remains high, at 71 percent. However, when detected late and cancer has spread to distant organs, five-year survival drops to 14 percent. There is substantial evidence supporting a role for screening in the reduction of CRC-related mortality and incidence. Full implementation of CRC screening could dramatically reduce the impact and costs associated with this cancer.1,2

Recommendations and guidelines published by organizations and specialty societies, including the U.S. Preventive Services Task Force and the American Cancer Society, strongly advocate for CRC screening. In an attempt to increase screening rates, a broad coalition of more than 900 organizations developed the “80% by 2018” screening campaign. Despite these efforts, CRC screening rates remain suboptimal. One-third of Americans, or 23 million, who should be screened for colorectal cancer refuse screening. The American Cancer Society estimates that more than 10,000 American lives would be saved each year if screening rates improved by 15 percent.1

Here we describe a routine clinical encounter in which a molecular blood screening test for circulating cell-free tumor DNA,3,4 approved by the Food and Drug Administration in 2016 (Fig. 1), prompted a patient who had missed his screening to undergo colonoscopy.

Case. An asymptomatic 70-year-old white male, who was noncompliant and overdue for his regular colonoscopy, received a screening test for circulating methylated SEPT9 DNA (Epi proColon, Epi­genomics) and the result was positive. He had no personal or family history of colorectal cancer. Fifteen years prior, at colonoscopy, the patient had a small adenomatous polyp and a single hyperplastic colonic polyp removed. Two subsequent colonoscopies, at five-year intervals each, were negative for polyps and cancer. Upon learning of his positive methylated SEPT9 blood test result, he contacted his gastroenterologist to schedule a colonoscopy, which was performed within four weeks. The colonoscopy revealed 10 polyps, all benign; nine were hyperplastic and one was a diminutive sessile serrated adenoma. Colorectal cancer was not found.

Fig. 1. Workflow for the analysis of methylated SEPT9 from cell-free plasma DNA using the Epi proColon test kit. DNA was isolated from plasma by magnetic particles, then subjected to bisulfite conversion of unmethylated cytosines. In the unmethylated case, a blocker oligonucleotide prevents amplification of the target and the methylation-specific probe binds only to amplified methylated product. The qPCR amplification signal is read (Applied Biosystems 7500) and reported as positive or negative.

Discussion. These results are not unexpected since adenomatous polyps are frequently found in patients with a positive methylated SEPT9 test who do not have cancer.3,4 The results are also consistent with the large body of data supporting the significant difference in prevalence between adenomas and cancer across all screening-age-eligible groups.5,6 As the detection and removal of precancerous lesions prevents CRC,7,8 the referral of this patient for a diagnostic colonoscopy achieved the desired medical outcome.

The intended use of methylated SEPT9, under the FDA approval, is for those patients who have been offered other screening options (as per U.S. Preventive Services Task Force, 2008 guidelines) and have refused these forms of colorectal cancer screening. This patient decided to have the blood test based on the unremarkable results of two previous colonoscopies as well as interest in a novel molecular diagnostic technology. As it turned out, the positive methylated SEPT9 result prompted the patient to quickly undergo a colonoscopy.

This colon cancer screening test involves a simple blood draw and serves the purpose of bringing unscreened patients to the gold standard of screening, which remains colonoscopy and histopathology. The intended use of the product is for those one of three adults in the United States who refuse all forms of colon cancer screening. It is known from clinical trials that even those who repeatedly refused colon cancer screening will go on to colon­oscopy with a positive blood test result, and 99.5 percent of otherwise noncompliant patients will have their blood drawn for this test.9 Since the patient experience is a simple blood draw, this molecular diagnostic test holds great promise as a key to bringing the unscreened in for screening and medical care to prevent deaths from advanced colon cancer.

  1. Colorectal cancer facts and figures 2017. American Cancer Society website. http://bit.ly/CRC-facts-figures.
  2. Cancer stat facts: colorectal cancer. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER) website. http://seer.cancer.gov/statfacts/html/colorect.html.
  3. Potter NT, Hurban P, White MN, et al. Validation of a real-time PCR-based qualitative assay for the detection of methylated SEPT9 DNA in human plasma. Clin Chem. 2014;60(9):1183–1191.
  4. Johnson DA, Barclay RL, Mergener K, et al. Plasma Septin9 versus fecal immunochemical testing for colorectal cancer screening: a prospective multicenter study. PLOS One. 2014;9(6):e98238.
  5. Corley DA, Jensen CD, Marks AR, et al. Variation of adenoma prevalence by age, sex, race, and colon location in a large population: implications for screening and quality programs. Clin Gastroenterol Hepatol. 2013; 11(2):172–180.
  6. SEER cancer statistics review (CSR) 1975–2014. National Cancer Institute. SEER website. https://seer.cancer.gov/csr/1975_2014. Updated April 2, 2018.
  7. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993;329(27):1977–1981.
  8. Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012;366(8):687–696.
  9. Liles EG, Coronado GD, Perrin N, et al. Uptake of a colorectal cancer screening blood test is higher than of a fecal test offered in clinic: randomized trial. Cancer Treat Res Commun. 2017;10:27–31.

Dr. Potter is director of reimbursement and medical affairs, Epigenomics, Germantown, Md. Dr. Bhinder, a gastroenterologist, is with Capital Digestive Care, Rockville, Md. Dr. Cossman, a pathologist, is a consultant in Potomac, Md.

Test yourself: Here are three questions taken from the case report.

Answers are online now at www.amp.org/casereports and will be published next month in CAP TODAY.

1. The five-year survival for patients diagnosed with stage I CRC is closest to:

a. 10 percent
b. 35 percent
c. 50 percent
d. 90 percent

CAP TODAY
X