Raising colorectal cancer screening rates is a tough task

An accurate blood-based test to detect colorectal cancer is the key to lowering the mortality from this devastating disease

 

 

In 2018 there were an estimated 140,250 new cases of colorectal cancer (CRC), and 50,630 estimated deaths, from this preventable disease. The National Cancer Institute’s SEER data for Colorectal Cancer (Surveillance, Epidemiology and End Results Program) has encouraging trend-lines, however. Among adults 50 and older in the US, CRC incidence and mortality rates have dropped by 32% from 2000 to 2013. However, disturbingly, CRC incidence and mortality among those less than 50 years in age have actually risen in that same timeframe by 22%. (Seigel et al CA Cancer J Clin 2017.)

Why is CRC considered preventable? If it is caught early, the 5-year survival is greater than 90%. If it is caught at an advanced state, the 5-year survival plummets to less than 20%.

National campaigns to raise the screening rate of colorectal cancer

Several organizations, such the National Colorectal Cancer Roundtable, have launched efforts to raise awareness of the importance of CRC screening. In 2014 they announced a “80 by 2018” campaign to get compliance with CRC screening to 80%, and have documented their progress to this goal. Yet the overall screening rate remains at approximately 67% in 2017 (Seigel op. cit.).

One company, Exact Sciences of Wisconsin has popularized their stool-based FIT+DNA test. FIT stands for Fecal Immunohistochemical Test looking for blood in the stool. The DNA test interrogates DNA mutations in the KRAS gene (well-known to be associated with CRC) as well as the methylation status eight CpG sites in the promoter of the BMP3 gene, and nine CpG sites in the promoter of the NDRG4 gene, where high methylation status is positively correlated with CRC assayed by real-time PCR. Undoubtedly their commercial success has come in-part with direct-to-consumer education (you can watch some of their television advertisements here) as well as their direct sales force educating physicians and healthcare providers..

Last summer, Exact Sciences signed a sales and marketing co-promotion agreement with Pfizer Inc. which broadens their commercial reach. For the year 2018 they announced completing 934,000 of their ColoGuard tests; however, in the US there are an estimated 27 million individuals ages 50-75 who have yet to be screened.

The inconvenience factor for screening options

We have looked here at “Why is stool such a difficult non-invasive starting material”. There are clear disadvantages to stool-based testing, not the least of which is the consumer-handling issue. Exact Sciences has stated publicly in their corporate presentation that a full one-third of their collection kits (available through prescription) do not get returned to them. Their marketing campaign of “Get. Go. Gone.” is made to appear easy and streamlined, nonetheless getting back only two-thirds of the collection kits sent out illustrates the difficulty in collecting and handling the sample.

FIT and gFOBT screening rates as of 2017 are only 7.3%, and require yearly screening; even though the US Protective Services Task Force expanded the number of types of tests they recommend in 2016 to six (up from two in 2008) the rate of screening has only been slowly increasing over this timeframe. The JAMA website has put together some interesting expert interviews as well as a well-produced ‘Whiteboard’ video here.

Human nature and human behavior are difficult to change, even if your life depends on it

These screening rates will increase, with the aforementioned commercial efforts as well as public education efforts. Nonetheless human nature is a stubborn thing. For example, in a Nashville Storytellers event, a woman named Heidi Hall describes in a remarkable video “living with cancer and how she reacted to her diagnosis”.  She states “I was more comfortable dying of cancer, than living with a colostomy.”

It is well-known that lowering risk factors for all cancers is something perhaps your mother told you often while growing up. Eat a diet high in vegetables and low in processed or fried foods. Do not be overweight. Exercise regularly. Do not smoke, and drink alcohol in moderation.  Lowering these behavioral risk factors will take a major public health effort, as obesity in the US continues to rise (most recent NHANES data indicates obesity is rising and currently at 31%).

Sensitivity and PPV statistics for the existing CRC blood-based test Epi proColon

There is on the market a blood-based, FDA approved colorectal cancer screening test called the Epi proColon Test offered by Epigenomics AG of Berlin Germany. The test interrogates the methylation status of the SEPT9 gene from a blood sample. Unfortunately this test, while offering the convenience of blood, suffers from low specificity, low sensitivity and low Positive Predictive value.

Laboratory Corporation of America (also known as LabCorp) offers the Epi proColon and put together this convenient explainer document (PDF) which states a sensitivity of 68.2%, a false-positive rate of 20%, and a Positive Predictive Value (PPV) of only 2.4%. The sensitivity indicates of people with CRC, 7 out of 10 people will test positive, and 3 out of 10 people will test negative even though they have CRC. Thanks to the high false-positive rate, only 2.4% of people who test positive will actually have CRC, or 1 in 30. That is a lot of follow-up screening (colonoscopy) that isn't needed - the cost of a colonoscopy to the healthcare system has been estimated to be $1,600 per procedure.

As a result, even though FDA approval was granted in 2016, there has been limited adoption and difficulties in getting reimbursement. In this GenomeWeb article from December 2018 (subscription required) they share the observation that in a public health-fair environment with collaborators at the University of Miami, the compliance rate with fecal CRC tests was only 15%, with a ‘over a fivefold increase in adoption with its blood test’ (or greater than 75%).

How Singlera’s ColonES compares

According to data from 1,283 samples tested with Singlera’s ColonES test in our Shanghai clinical laboratory, with a 97% sensitivity to CRC Stage I, and a 99% specificity. In addition, we show a 91% sensitivity to patients with advanced adenoma (PDF), of which it is known that 85% of these patients will progress to Stage I colorectal cancer.

Currently Singlera is in the development process, and looking for collaborators.

Interested in raising the colorectal cancer screening rates though a partnership? Feel free to contact us.

References:

  1. Siegel R.L. and Jemal A. et al 2017 Colorectal Cancer Statistics, 2017. PMID: 28248415 https://www.ncbi.nlm.nih.gov/pubmed/28248415
  2. Molika Ashford, GenomeWeb Premium, December 28 2018. "Epigenomics Pushes New Promotion Efforts for ProColon Test as Other Assays in Pipeline Advance" Link to article.