Management of High-Risk Patients

The National Comprehensive Cancer Network (NCCN) has established and published guidelines for cancer care that are focused on quality, effectiveness, and efficiency. The guidelines are continuously updated to reflect current research. Specific recommendations for screening and management of individuals with an increased lifetime risk of cancer due to hereditary colon cancer syndromes are briefly summarized below. Please note that most current and detailed guidelines are available through NCCN “Genetic/Familial High-Risk Assessment: Colorectal.”

NCCN recommendations for high-risk colon cancer genes, including genes implicated in Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) and polyposis genes (APC, MUTYH), have been established (NCCN v1.2015).

For Lynch syndrome, the surveillance guidelines do vary based on the gene in question:

  • MLH1/MSH2/EPCAM mutation carriers are advised to start colonoscopy every 1 to 2 years starting at age 20 to 25, women are recommended to consider prophylactic TAHBSO after childbearing (typically age 35 to 40), and upper endoscopy can be considered every 3 to 5 years starting at age 35 based on family history or in Asian populations due to their elevated gastric cancer risk.
  • For MSH6/PMS2 mutation carriers, colonoscopy is advised starting at age 25 to 30 every 1 to 2 years, prophylactic hysterectomy should be considered after age 40, and other cancer screening can be considered based on family history (these are thought to be lower than MLH1/MSH2 risks).
  • For APC, colonoscopy or flexible sigmoidoscopy is recommended annually starting age 10 to 15 until polyp burden is too great to clear effectively (at this point, total colectomy recommended); upper endoscopy starting at age 20 to 25 to evaluate stomach and duodenum; annual thyroid exam starting in the late teens; desmoid risk warrants annual abdominal palpation with possible imaging if needed.
  • For MUTYH, annual colonoscopy starting by age 21 or based on family history (if polyp burden too great to clear with colonoscopy, colectomy can be considered) with baseline upper endoscopy by age 35.
  • Other high-risk genes related to colon cancer include Peutz-Jeghers syndrome, juvenile polyposis, serrated polyposis syndrome, Li-Fraumeni syndrome and Cowden syndrome (PTEN Hamartoma Tumor syndrome).

NCCN also publishes colon cancer screening recommendations based on increased risk due to family history (Colorectal Cancer Screening v1.2015). Recommendations are based on number of first- or second-degree relatives diagnosed with colon cancer and ages at diagnosis. A first-degree relative with an advanced adenoma is also a consideration for altered colonoscopy screening recommendations. Individuals at an increased risk should discuss this information with their physicians to establish an appropriate screening routine.