With the identification of new genes, the knowledge of genetic susceptibility to gastrointestinal cancers is constantly evolving. Based on the emerging new evidence and expert consensus, a multidisciplinary panel of authors selected by the European Society for Medical Oncology (ESMO) released updated recommendations for the identification and management of patients with hereditary gastrointestinal cancers. This report was published in Annals of Oncology.

The authors performed a review of literature focused on the diagnosis, treatment, and follow up of hereditary colorectal cancer, gastric cancer, and pancreatic cancer. Recommendations were developed and graded in accordance with the ESMO Clinical Practice Guidelines and subjected to an anonymous peer-review process.

Recommendations for Hereditary Nonpolyposis Colorectal Cancer Syndrome (Lynch Syndrome)

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Diagnosis and Testing

In individuals with hereditary colorectal cancer, the ESMO recommends tumor testing with immunohistochemistry staining to detect lack of expression of corresponding mismatched repair proteins and/or microsatellite instability that occurs due to alterations in mismatched repair genes.

To rule out sporadic colorectal cancer, analysis of BRAF V600E mutation or methylation analysis of the MLH1 promoter is recommended for when loss of MLH1 expression is observed in the tumor.

If loss of MLH1 expression alone or concurrently with MSH2, MSH6, or PMS2 is observed, ESMO recommends germline genetic testing. DNA sequencing and analysis of large genetic deletions or rearrangements should be included in full germline genetic testing.

Surveillance and Prevention

Surveillance colonoscopy is recommended every 1 to 2 years in asymptomatic individuals with Lynch Syndrome.

In patients with Lynch Syndrome who have a family history of gastric cancer, or in regions associated with high gastric cancer incidence, surveillance with upper endoscopy is indicated every 1 to 3 years starting between the ages of 30 and 35 years.

In women with Lynch Syndrome, annual gynecological surveillance is recommended between the ages of 30 and 35 using transvaginal ultrasound, cancer antigen 125 analysis, and endometrial biopsy. ESMO recommends prophylactic hysterectomy with bilateral oophorectomy as an option for female carriers who are postmenopausal or who are done childbearing.

ESMO suggests that a daily aspirin regimen may be considered as a cancer prevention measure in individuals with Lynch Syndrome, although the optimal dose has not yet been determined. Individuals at risk for colorectal cancers should further refrain from smoking and maintain a healthy weight.

Cancer Treatment

An extended colectomy may be considered in individuals with Lynch Syndrome who are already undergoing primary surgery for colorectal cancer, especially in younger individuals.

ESMO does not make any recommendations for chemotherapy based on mismatch repair or microsatellite instability status; however, mismatch repair-deficient cancers may be sensitive to immunotherapy, specifically pembrolizumab and nivolumab.

Recommendations for Hereditary Polyposis Colorectal Cancer Syndromes

Diagnosis and Testing

Panel germline genetic testing should be considered in individuals with multiple colorectal adenomas (>100) and doctors should test for mutations found in APC, MUTYH, POLE, POLD1, and NTHL1 genes. APC analysis should further include detection of large genetic rearrangements.

Surveillance and Prevention

In individuals with classical familial adenomatous polyposis (FAP), ESMO recommends that flexible sigmoidoscopy or colonoscopy should be carried out every 1 to 2 years starting in adolescence (between the ages of 12 and 15 years). Regular colonoscopic surveillance is recommended once adenomas are detected up until colectomy is planned.

In families with attenuated FAP (AFAP), colonoscopy should be carried out every 1 to 2 years starting between the ages of 18 and 20 years and may be continued lifelong in mutation carriers. ESMO suggests that some patients with AFAP can be conservatively managed with annual colonoscopy and polypectomy.

In both classic FAP and AFAP, surveillance for extracolonic manifestations (gastroduodenal polyposis, thyroid cancer, desmoid tumors) is recommended every 5 years when colorectal polyposis is first diagnosed or starting at the age of 25 to 30 years, whichever comes first.

The surveillance protocol for MUTYH-associated polyposis, or individuals carrying mutations of the MURYH gene, is similar to that for AFAP: first colonoscopy is recommended between ages 18 and 20 years and should be repeated every 1 to 2 years.

Cancer Treatment

ESMO recommends surgery in most polyposis cases if there are large numbers of adenomas, although some patients with AFAP can be conservatively managed using colonoscopic surveillance.

Classic colorectal surgery used to treat FAP (total colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis) is recommended before the age of 25 years. The type of surgery depends on the patient’s age at diagnosis, severity of rectal polyposis, presence of rectal polyps, and the risk of developing desmoid tumors. Surveillance of the rectum or pouch is recommended after colorectal surgery.

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Recommendations for Hereditary Gastric Cancer

Diagnosis and Testing

ESMO recommends germline genetic testing for CDH1 in families with clinical criteria of hereditary diffuse gastric cancer (2 or more confirmed cases of gastric cancer at any age in first- or second-degree relatives, with at least 1 case of diffuse gastric cancer; personal history of diffuse gastric cancer before the age of 40 years; or personal or family history of diffuse gastric cancer and lobular breast cancer, with at least 1 diagnosis made before the age of 50 years).

Surveillance and Prevention

In asymptomatic carriers of a pathogenic germline CHD1 mutation, prophylactic gastrectomy is recommended; in individuals aged between 20 and 30 years, annual endoscopic surveillance is recommended. Women carrying the CHDI mutation should also receive annual breast magnetic resonance imaging (MRI) with mammography beginning at age 30 years.

Recommendations for Hereditary Pancreatic Cancer

Diagnosis and Testing

ESMO recommends confirming pancreatic cancer using germline genetic testing with a multigene cancer panel (BRCA1, BRCA2, PALB2, CDKN2A), especially in families with a strong clustering of pancreatic cancer.

Surveillance and Prevention

Annual endoscopic surveillance or pancreatic MRI is recommended in patients at high risk for pancreatic cancer. High-risk patients are those with 3 or more blood relatives with pancreatic cancer, with at least 1 affected first-degree relative; those with 2 affected first-degree relatives; those with Peutz-Jeghers syndrome regardless of family history; or those who are carriers of CDKN2A/p16, BRCA2, PALB2, or mismatch repair gene mutations with at least 1 affected first-degree relative.

Multiple authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Stjepanovic N, Moreira L, Carneiro F, et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published online August 5, 2019]. Ann Oncol. doi: 10.1093/annonc/mdz233

This article originally appeared on Gastroenterology Advisor