NCCN Advocates for Universal Lynch Syndrome Screening in Newly Diagnosed Colorectal Cancer


Key Points

  • The National Comprehensive Cancer Network (NCCN) has developed guidelines for familial/genetic colorectal cancer assessment.
  • NCCN recommends that newly diagnosed colorectal cancer patients be screened for Lynch syndrome, which is detected in one out of 35 patients with this disease.

The National Comprehensive Cancer Network (NCCN) is recommending that newly diagnosed colorectal cancer patients be screened for Lynch syndrome, previously called hereditary nonpolyposis colorectal cancer. The NCCN’s proactive position should greatly help identify individuals and their relatives at high risk for a primary or secondary cancer, said Heather Hampel, MS, a genetics counselor who spoke on genetic and familial colorectal cancer risk at the NCCN 19th Annual Conference held March 13-15, 2014, in Hollywood, Florida.

Ms. Hampel is Associate Director of the Division of Human Genetics and Professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

New Guidelines for Genetic/Familial High-Risk Assessment in Colorectal Cancer

This recommendation is one of the key components of the 2014 NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Colorectal Cancer. Lynch syndrome is detected in 1 out of 35 patients with newly diagnosed colorectal cancer.

Notably, the guidelines now exist under their own cover, paralleling those previously established for the assessment of genetic and familial breast cancer. Prior to 2014, the detection and management of hereditary colorectal cancer fell under the NCCN Colorectal Cancer Screening Guidelines.

“We felt the information about the genetic and familial colorectal cancer syndromes had grown, and this is not where clinicians were looking for it,” Ms. Hampel said in an interview with The ASCO Post. “We are positioning ourselves for the day when there is a set of hereditary cancer guidelines that includes all inherited syndromes, not just breast and colon.”

Differential Diagnosis of Colorectal Cancer Syndromes

The differential diagnosis of hereditary colon cancer begins with determining the number of polyps. Patients with fewer than 10 colorectal polyps should be considered for Lynch syndrome, familial colorectal cancer syndrome type X, or MYH-associated polyposis. This group is further differentiated according to two genetic pathways, where they are determined to have chromosome instability (85%) or microsatellite instability (15%); of the latter group, 2% to 3% have Lynch syndrome, while the rest are microsatellite instability–positive.  

The determination of microsatellite instability positivity of the presence of Lynch syndrome is important because these conditions have implications for surveillance and treatment, she said.

Microsatellite instability–positive patients have a better prognosis, and, at least in the future, may be candidates for treatments other than those based on fluorouracil, which has little impact in this form of colorectal cancer. Lynch syndrome patients are at high risk for secondary primary cancers and have at-risk relatives who should also be screened.

Patients with more than 10 polyps are evaluated genetically for various polyposis syndromes, she added.

Screening for Lynch Syndrome

Universal screening for Lynch syndrome has been a topic of discussion in oncology and gastroenterology circles for several years, but a formal recommendation by the NCCN moves the concept forward, Ms. Hampel said. Almost three-fourths of NCCN centers have begun conducting universal screening for all new colorectal cancer patients. 

In the 2014 guidelines, the testing for Lynch syndrome is separated into two sections: clinical testing criteria for Lynch syndrome, based on personal and family history, and routine tumor testing criteria for Lynch syndrome.

For a clinical diagnosis of Lynch syndrome, at least three relatives must have a cancer associated with the condition—ie, colorectal, endometrial, small bowel, ureter, or renal-pelvis cancer—in addition to all of the following criteria:

  • One relative must be a first-degree relative of the other two.
  • At least two successive generations must be affected.
  • At least one relative with a Lynch syndrome–associated cancer should be diagnosed before age 50.
  • Familial adenomatous polyposis should be excluded.
  • Tumors should be verified whenever possible.

“But family histories can be deceiving,” Ms. Hampel cautioned. “Family size is getting smaller, and the wider use of colonoscopy is likely to prevent many colon cancers. Patients often don’t know who in their family had cancer, much less polyps. This makes it harder to diagnose Lynch syndrome on the basis of family history today. Therefore, we have an interest in screening all colon cancer patients.”

Aside from patients diagnosed this year, who received routine screening, there are many families of patients diagnosed years ago who have not been identified. “This is why there are two pathways: one for the newly diagnosed, where we screen them all, and the other that involves family history,” she explained.

The tests that screen tumors for Lynch syndrome include microsatellite instability testing, which is positive in 15% of colorectal cancer cases and in up to 89% of Lynch syndrome cases; immunohistochemistry staining, which has a 96% correlation with microsatellite instability positivity; and methylation testing, which detects acquired methylation that is generally not inherited; 20% will be found to have Lynch syndrome.

Ms. Hampel added that the only potential “harm” in universal screening is the possibility of insurance discrimination; however, the Genetic Information Non-Discrimination Act protects patients against obstacles with health insurance or employment, she said.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.