New Guidelines Target Cancer Risk in Rare GI Syndromes

In a new set of guidelines, the U.S. Multi-Society Task Force on Colorectal Cancer offers various approaches to the diagnosis and management of cancer risk in patients with gastrointestinal

hamartomatous polyposis syndromes.

Published in Gastroenterology, the recommendations from the task force -- led by C. Richard Boland, MD, of the University of California San Diego -- focus on the genetic evaluation,

endoscopic surveillance, and best treatment practices for children and adults with these rare disorders, which are associated with an increased risk of colorectal cancer and other benign and

malignant tumors in the digestive and non-digestive organs.

Hamartomatous polyposis syndromes comprise a variety of disorders -- juvenile polyposis syndrome (JPS), Peutz-Jeghers syndrome (PJS), hereditary mixed polyposis syndrome, as well as PTEN

hamartoma tumor syndromes (PHTS) such as Bannayan-Riley-Ruvalcaba syndrome and Cowden's syndrome.

"Each hamartoma syndrome presents a different cancer risk and requires a different surveillance approach, making genetic testing a critical tool in cancer prevention," Boland told MedPage

Today. "By understanding a patient's unique genetic makeup, we can craft personalized cancer surveillance plans to prevent cancer progression and save lives."

Included in the recommendations are genetic evaluations -- and multigene panel test if warranted -- for those with at least two hamartomatous polyps, a family history of hamartomatous

polyps, or a first- or second-degree relative with a hamartomatous polyposis syndrome-related cancer.

"The consensus statement is comprehensive and summarizes the literature on the clinical features and cancer risks and provides guidance for clinicians regarding the molecular genetics of

these disorders, approach to patient diagnosis, and importantly the suggested management of individuals with these syndromes," said co-author Carol A. Burke, MD, of the Cleveland Clinic.

"There is a helpful focus on the endoscopic surveillance, which plays a key role in the prevention or early detection of cancer and treatment of other polyp-related symptoms," said Burke.

The guidelines establish a starting point for future research opportunities for this population, the authors noted, since all recommendations were based on a low quality of evidence, as

defined by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

"These new recommendations are significant because they give specific guidance to this small subset of patients to look for genetic syndromes that may be important to them and to their

family members," said David Greenwald, MD, of Mount Sinai Hospital in New York City, who was not involved in this recommendations. "This is an excellent example of personalized medicine."

Other recommendations included genetic testing for the STK11 gene for any individual with at least two histologically-confirmed PJS polyps, a family history of PJS in a first-degree relative

or those with a family history of PJS-related mucocutaneous pigmentation, including any number of polyps. PJS patients presenting a greater cancer risk should undergo a multidisciplinary

surveillance of the breast, stomach, colon, small bowel, pancreas, testes, ovaries, and lungs.

PJS patients should receive small bowel surveillance with magnetic resonance enterography (MRE) or video capsule endoscopy between ages 8 to 10, or prior if symptomatic. If no polyps are

found, surveillance at age 18 is recommended, followed by every 2-3 years.

Between ages 8 and 10, an upper gastrointestinal endoscopy should be performed to surveil the stomach, colon, and duodenum in PJS, which can occur at capsule placement during small bowel

surveillance or if MRE detects polyps. Small bowel PJS polyps that are ≥10 mm or symptomatic should be removed to prevent bleeding complications or intussusception.

Starting at age 35, pancreatic screening is recommended for PJS using endoscopic ultrasound or magnetic resonance cholangiopancreatography.

For JPS, a genetic evaluation is recommended for those with at least five colon or rectal juvenile polyps or at least two other gastrointestinal polyps and for those with any polyps who have

a first-degree relative with JPS.

JPS patients should undergo surveillance of the stomach and colon with colonoscopy or upper endoscopy starting at age 12-15, or sooner if symptomatic, followed by every 1-3 years. At

diagnosis, JPS pathogenic variants of SMAD4 should be screened for hereditary hemorrhagic telangiectasia, including for cerebral and pulmonary arteriovenous malformations.

Individuals with multiple ganglioneuromas or gastrointestinal hamartomas should be genetically evaluated for Cowden's syndrome and other PHTS-related conditions.

For PHTS, multi-disciplinary cancer surveillance is recommended for the skin, thyroid, breast, uterus, kidney, and colon.

Colonoscopy surveillance for PHTS should start at age 35 and repeat at least every 5 years, "depending on polyp burden."

"I think we still have a long way to go before we understand fully why these syndromes (PJS and JPS) create relatively minor problems in childhood (bleeding and gut obstruction), whereas in

adult life, these [patients] have a very high risk of cancer, and in the case of PJS, the cancer risk is not in the place where the pediatric polyps occur," Boland told MedPage Today.

Coauthors disclosed relationships with Amadix, Aries Pharmaceuticals, Cancer Prevention Pharmaceuticals, CellMax, Covidien, Ferring Pharmaceuticals, Dark Canyon, DC Health, ERBE USA,

Freenome Holdings, GI, Guardant Health, GlaxoSmith Kline, Iterative Scopes, Janssen Pharmaceuticals, Mallinckrodt Pharmaceuticals, Motus, Myriad Genetics, Olympus America, Pfizer, Remedy

Partners, Salix Pharmaceuticals, and SLA Pharma AG.