Family History of Bowel Cancer?, Information for Health Professionals, Lynch Syndrome, Polyposis, Screening Guidelines

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

English: Original Logo of the Society

English: Original Logo of the Society (Photo credit: Wikipedia)

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

3 Diagnosis, management and counselling of hereditary colorectal cancer

All patients with CRC should have a collection of family history regarding polyps and any type of cancer (at least first and second-degree relatives) [V, A]. About 5% of CRC are of hereditary origin. If a clinical suspicion of polyposis or Lynch syndrome is made, the patient should be referred to a specialist in human genetics [V, C]. Average-risk populations should have an organized access to population-CRC screening, if resources are available at national level [V, A]. Methodology and choice of screening modality is a matter of discussion. An overview of management of hereditary CRC syndromes is summarized in Table 2.

View this table:

Table 2.

Management of hereditary colorectal cancer

3.1 Lynch syndrome

Clinical suspicion is based on fulfilment of clinical criteria (Amsterdam, Bethesda) or on an altered molecular screening [microsatellite instability (MSI) and/or immunohistochemistry (IHC) for mismatch repair proteins (MMR)] in the context of a suggestive personal or family history [III, B].

3.1.1 Detection of mutation

Germline genetic testing will be performed according to the results of molecular screening (MSI and/or IHC of MMR). If a tumour block is not available, the gene-specific prediction models may help to guide a genetic strategy [III, B].

If loss of MLH1 expression is observed (especially in non-familial cases), somatic hypermethylation of the MLH1 promoter should be considered, which can be ruled out by testing the somatic BRAF V600E mutation or analysis of hypermethylation of the MLH1 promoter [III, B].

Full germline genetic testing should include DNA sequencing and large rearrangement analysis of the MMR genes [I, A]. Adequate pre- and post-test genetic counselling should always be performed.

3.1.2 Surveillance for healthy mutation carriers

For individuals with Lynch syndrome carrying an MLH1 or MSH2 mutation, colonoscopy should start at the age of 20–25 years and should be repeated every 1–2 years [II, A].

No specific upper limit for surveillance endoscopies is established and it should be based on the individual’s health status.

For healthy individuals with Lynch syndrome carrying an MSH6 or PMS2 mutation, colonoscopy should start at the age of 30 years and be repeated every 1–2 years. Again, no specific upper limit is established [II, A].

Endometrial and ovarian cancer screening may be performed on a yearly basis starting at the age of 30–35 years with gynaecological examination, pelvic ultrasound, analysis of CA125 and aspiration biopsy [IV, C]. Pros and cons should be adequately discussed with the individual subject at risk given the evidence of benefit only from observational studies.

Surveillance for other Lynch-associated cancers is recommended on the basis of the family history and may include upper endoscopy, abdominal ultrasound and urine cytology from the age of 30–35 years in a 1–2-year interval [IV, C].

3.1.3 Chemoprevention

Neither specific chemoprevention nor specific dietary interventions is being recommended at the current time in individuals with Lynch syndrome to prevent CRC, although data are emerging supporting the use of aspirin [7] [II, B].

3.1.4 Risk reduction: prophylactic surgical options

Prophylactic colectomy in healthy mutation carriers is not recommended. Prophylactic gynaecological surgery might be an option in female carriers from the age of 35 onwards and after childbearing is completed [IV, C].

3.1.5 Cancer treatment

The need for intensive surveillance after surgery versus the option of an extended colectomy should be discussed at the time of diagnosis of an advanced adenoma or CRC, especially in young patients [IV, C]. For female CRC patients with good prognosis, surveillance/surgical options for gynecological cancer should also be discussed. Chemotherapy regimens are the same as those for sporadic CRC.

3.2 Familial colorectal cancer × syndrome

Relatives of individuals with CRC who fulfil the Amsterdam criteria and who do not exhibit MMR deficiency have a moderate risk of CRC. Surveillance would include colonoscopy at a 3–5-year interval, starting 5–10 years before the youngest case in the family. Surveillance of extra-colonic cancers is not recommended.

3.3 FAP

Clinical diagnosis of classical familial adenomatous polyposis (FAP) is based on the identification of >100 colorectal adenomas. Lifetime risk of development of CRC is 100%.

3.3.1 Attenuated FAP

Clinical diagnosis of attenuated FAP is based on the following criteria:

  • at least two patients with 10–99 adenomas at age >30 years; or

  • one patient with 10–99 adenomas at age >30 years, a first-degree relative with CRC and few adenomas and no family members with >100 adenomas before the age of 30 years.

3.3.2 Genetics

Genetic testing (germline adenomatous-polyposis-coli (APC) mutation) should start by investigating the affected individual. If the causative mutation is detected, pre-symptomatic diagnosis can be offered to at-risk family members. When the causative mutation is not identified, all at-risk family members should undergo colorectal endoscopic screening [V, C].

3.3.3 Colorectal screening

In families with classic FAP, flexible sigmoidoscopy is an adequate technique and it should be performed every 2 years, starting at the age of 12–14 years, and continued lifelong in mutation carriers [V, C]. If adenomas are found, colonoscopy should be done annually until colectomy.

In families without an identified APC mutation, surveillance should be performed every 2 years until the age of 40, and be repeated every 3–5 years between 40 and 50 years and may continue with general screening at age 50 if no polyposis has developed [V, C]. When an attenuated form is suspected, total colonoscopy is needed. In this setting, examination should be performed every 2 years until polyposis is diagnosed. Screening should be started at the age of 18–20 years and continued lifelong.

3.3.4 Screening for extra-colonic manifestations

It should start when colorectal polyposis is diagnosed or at the age of 25–30 years, whichever comes first [V, C].

Gastroduodenal endoscopy should be performed every 5 years until adenomas are detected [V, C]. Screening for thyroid cancer should be performed by annual sonography of the neck [V, C]. Regular physical examination and if indicated abdominal CT should be performed in search for desmoid tumours [V, C]. Screening for other extra-colonic manifestations is not justified because of their low prevalence and/or limited clinical impact. Since gastrointestinal adenomas may also develop in the jejunum and ileum, it has been suggested that regular screening by barium contrast series or wireless capsule endoscopy could be performed [V, C].

3.3.5 Treatment

Surgical resection is the standard of care in patients with classical FAP [IV, A]. It can be considered in some patients with an attenuated form. Surgical resection includes either total colectomy with ileoanal pouch anastomosis or subtotal colectomy with ileorectal anastomosis, once adenomas are detected [IV, C]. Duodenal adenomas are managed with endoscopic polypectomy, and in Spigelman stage IV (see below), duodenal–pancreatectomy may be considered. Because of the high recurrence rate of desmoid tumours, surgical resection should be delayed unless complications occur. The first-line treatment in patients with large or growing intra-abdominal or abdominal wall desmoid tumours is based on, e.g COX 2 inhibitors, tamoxifen and tyrosine kinase inhibitors.

3.3.6 Surveillance for healthy mutation carriers


Regular endoscopic surveillance every 6–12 months after subtotal colectomy is recommended to detect rectal adenoma recurrence [V, C]. When total colectomy is performed, surveillance of the pouch can be repeated every 1–2 years. In patients with attenuated FAP conservative management with endoscopic polypectomy, examination of the entire colon and rectum should be performed annually [V, C].


Surveillance of duodenal manifestation will depend on its extension. When it corresponds to Spigelman stage I or II, upper endoscopy should be performed every 5 or 3 years, respectively, and every 1–2 years in stage III or every 6 months in stage IV [IV, C].

3.4 MUTYH-associated polyposis

MUTYH-associated polyposis (MAP) is inherited as an autosomal recessive trait with high penetrance. Clinically, MAP resembles the attenuated form of FAP syndrome, with an average age of onset around the mid-50s with often <100 adenomas and, accordingly, patient management is very similar.

3.4.1 Screening for family members

Individuals should undergo total colonoscopy every 2 years, starting at the age of 18–20 years and continuing lifelong [V, C]. Genetic testing allows the most cost-effective screening to be performed by focussing colorectal examinations only on gene carriers. However, when the causative mutation is not identified, all at-risk family members should undergo colorectal screening.

3.4.2 Treatment for healthy gene carriers

Colorectal management is similar to that proposed for patients with attenuated FAP.

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

Table 2.

Management of hereditary colorectal cancer

Syndrome Diagnosis of index case (with cancer) Management of the affected individual (with cancer) Management of individuals at high risk (healthy mutation carriers or individuals at 50% risk of being mutation carrier)
Clinical Molecular screening (tumour tissue) Germline genetic testing (blood) Treatment Follow-up Cancer risk Surveillance Germline genetic testing (blood)
Lynch Amsterdam, Bethesda MSI and/or IHC for MMR proteins MLH1, MSH2
  • Tumour resection

  • Discuss colectomy, especially in young patients

Yearly endoscopy of the remnant colon or rectum High
  • Colonoscopy q 1–2 years, starting age 25 (30 years in case of MSH6 or PMS2 mutations)

  • Annual pelvic examinations, transvaginal ultrasound, ca125, endometrial biopsy in females, starting age 30–35 years

Direct genetic testing of the mutation identified in the family
Familial CRC X Amsterdam, Bethesda No MMR deficiency Unknown As average population As average population Moderate only CRC
  • Colonoscopy 1 3–5 years, starting 5–10 years before youngest case in the family.

FAP Colonoscopy: >100 adenomas none APC
  • Total or subtotal colectomy when adenomas occur

  • Endoscopic removal of duodenal adenomas

  • After subtotal colectomy: rectal examination q 6–12 m

  • After total colectomy: pouch exam. q 1–2 years

  • Duodenoscopy from 6 months to 5 years according to Spigelman stage

  • Thyroid examination yearly

  • Flexible sigmoidoscopy q 2 years, starting age 12–14 years until diagnosis of adenomas

  • If no mutation identified in the family: Flexible sigmoidoscopy q 2 years until 40 years, then q 3–5 years until 50, then general population screening

Attenuated FAP (aFAP) Colonoscopy:

  1. 2 relatives 10–99 adenomas (>30 years of age)

  2. 1 relative of CRC patient with 10–99 adenomas (>30 years of age)

  • Total or subtotal colectomy when adenomas occur.

  • Endoscopic removal of duodenal adenomas

As above High
  • Colonoscopy q 2 years, starting age 18–20 years, lifelong in mutation carriers.

  • APC, adenomatous-polyposis-coli; MSI, microsatellite instability; MMR, mismatch repair proteins; CRC, colorectal cancer; FAP, familial adenomatous polyposis; aFAP, attenuated FAP; MAP, MUTYH-associated polyposis.

via ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making.


About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

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