Colorectal Cancer — Developments in Screening and Detection

Sisco, Kenneth, MD, PhD
Medical Director
Quest Diagnostics Nichols Institute
Chantilly, VA
Also by this Author 

Colorectal cancer (CRC) is the fourth most common cancer among men and women and the second leading cause of cancer deaths. Screening is highly effective at reducing the incidence and mortality of colorectal cancer, yet a significant proportion of the population is not being screened.2

Dr. Kasinathan Muralidharan, Senior Director Molecular Genetics, Quest Diagnostics Nichols Institute and Dr. Kenneth Sisco, Medical Director, Quest Diagnostics Nichols Institute, review the importance of screening for colorectal cancer and discuss a newly available molecular test using peripheral blood that may help increase colorectal testing adherence.

The Case for Screening

“Colorectal carcinoma is a major killer that can be largely prevented,” says Dr. Sisco. “Pre-cancerous lesions and early stages of cancer are easiest to treat.  Once cancer has developed and spreads, it’s very difficult to treat. Most colorectal carcinomas start out as benign pre-cancerous growths that gradually transform to cancer.” When colorectal cancers are detected at an early, localized stage, the five-year survival is 90%, but only two of every five patients with colorectal cancers are diagnosed at this stage. Five-year survival of patients with advanced stages of colorectal cancer is 12%.3

The U.S. Preventive Services Task Force recommends colorectal cancer screening for men and women aged 50 through 75 years using high-sensitivity fecal occult blood testing (FOBT) including fecal immunochemical tests (FIT), sigmoidoscopy, or colonoscopy.4 “Rates for colorectal cancer testing are only around 50%,” notes Dr. Muralidharan. “While colonoscopy rates have increased in recent years, many patients remain unwilling to undergo the procedure due to the inconvenience and discomfort involved. From a public health perspective, we need to get more people tested.  There are barriers to testing so overcoming these barriers is critically important. Both the FOBT/FIT and colonoscopy represent fairly high barriers, so anything, which can help patients take that first step to colorectal cancer screening is valuable.”

ColoVantage®- A Convenient Blood Test to Aid in the Detection of Colorectal Cancer

One test that has recently become available that could help patients take that first step and may help increase colorectal testing adherence is ColoVantage. “ColoVantage has two important features,” explains Dr. Muralidharan. “First, the specimen is derived from a simple blood draw, as opposed to either stool or a tissue sample. Second, the marker it uses is DNA circulating in plasma, derived from a blood specimen. What the test detects is not an inherited change in DNA from a parent, but an alteration known as methylation of DNA segment. This DNA segment is a gene called ‘Septin 9’. This particular methylated DNA marker has been proven in multiple clinical studies to be highly correlated with the presence of colorectal cancer.”

“Our objective is to help get people to undergo the colonoscopy that will most likely benefit from the procedure,” notes Dr. Sisco. “Anyone who’s 50 years and over, and has resisted getting their first colonoscopy would be a good candidate for having this test. If he or she is positive, there’s a greater chance they will accept getting a colonoscopy - it heightens the need for having the colonoscopy and finding out if there is a lesion present.”

Understanding ColoVantage Test Results

“The negative predictive value of ColoVantage is over 99%, so it has the tremendous advantage of ruling out the presence of disease if it’s negative,” notes Dr. Muralidharan.  “This means that a person with a negative test result is highly likely not to have colorectal cancer.   

“A positive test result indicates an increased probability of colorectal cancer.  This result serves to categorize a patient as being at increased probability of having colorectal cancer.

Case-control studies are used to identify factors that may contribute to a medical condition by comparing people who have that disease with patients who do not have the disease but are otherwise similar.A case-control study we performed showed that the test has a sensitivity of 70% for colorectal cancer detection at a specificity of 89%. Sensitivity refers to the probability that someone with colorectal cancer will test positive.  Specificity refers to the probability that someone without colorectal cancer will test negative. A prospective study of about 8,000 CRC screening eligible individuals tested using the same marker in a  similar test has demonstrated a sensitivity of 67% and a specificity of 88%.

“The most important thing is that patients get tested. A positive ColoVantage test result should encourage the person tested to obtain a colonoscopy.”

An Evolving Field

Dr. Sisco and Dr. Muralidharan both expect that increased understanding of colorectal cancer will lead to continued developments in diagnostics and therapeutic agents. “Most colorectal carcinomas are sporadic, meaning they occur randomly without being inherited from one’s family,” says Dr. Sisco. ”We don't know the cause. We suspect that mutations (changes in the DNA of cells in the colorectum) occur, and that some people may be more prone to it, but we don’t fully understand the pathway.”

“While we certainly need new therapies, we mustn’t lose sight of the importance of screening tests,” adds Dr. Muralidharan. “Colorectal cancer is a disorder where early detection can make a big difference in reducing deaths. The 5 year survival rate for a person detected at an early stage is 90%. Detecting and removing a small benign lesion or early stage cancer is much more effective than treating cancer. So if we can improve colorectal cancer screening compliance, detect cancerous changes, and remove any growths early, the resulting success in reducing cancer deaths will be considerable. We can save a lot of lives by increasing early detection rather than waiting for an improvement in the cure of advanced disease.”

References

  1. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012.
  2. Colorectal Cancer Facts & Figures 2011-2013. American Cancer Society.
  3. SEER Stat Fact Sheets: Colon and Rectum. National Cancer Institute. National Institutes of Health.http://seer.cancer.gov/statfacts/html/colorect.html
  4. Colorectal Cancer Screening Tests. Centers for Disease Prevention and Control.
    http://www.cdc.gov/cancer/colorectal/basic_info/screening/tests.htm