New approaches to managing familial adenomatous polyposis (FAP)

Polyps are clusters of cells that can develop in the entire gastrointestinal tract, but they’re more likely seen in the small intestine, colon and/or rectum. As they grow, they can transform into cancer.

“Not every polyp turns into cancer. But since they have the potential to, we remove them,” says Eduardo Vilar-Sanchez, M.D., Ph.D., who specializes in hereditary cancer syndromes and colorectal cancer.

Familial adenomatous polyposis increases colorectal cancer risk

A hereditary genetic condition called familial adenomatous polyposis (FAP) causes an individual to grow hundreds, and sometimes thousands, of polyps throughout the gastrointestinal tract. People who carry the FAP genetic mutation have an increased risk for cancer, including thyroid cancer and a malignant soft tissue sarcoma called desmoid tumors. But the greatest risk is colorectal cancer.

“It’s like playing the lottery,” Vilar-Sanchez says. “Instead of one ticket, you have hundreds, so you’re increasing the odds.”

Although the genetic mutation is rare and only makes up for 1% of colorectal cancer cases, patients with FAP have a 100% likelihood of developing colorectal cancer by age 30, Vilar-Sanchez says. Individuals without a genetic mutation have a 5% likelihood of facing the same diagnosis in their lifetime.

Genetic testing and cancer screenings help diagnose and manage FAP in early life

FAP is a clinical diagnosis that is confirmed with genetic testing. If there is a known family history of FAP, a child may receive genetic testing as early as age 10. Although polyps are typically seen in the general population in their 50s and 60s, they can appear starting in the teenage years in individuals with the FAP mutation.

If FAP is confirmed, the patient will need a colonoscopy every year or sometimes more frequently. Patients may also receive an upper endoscopy to check for polyps in the upper gastrointestinal tract as well as imaging to check for desmoid tumors in the abdomen.

Surgery and chemoprevention manage risk in adult patients with FAP

To stop a polyp from becoming cancer, it must be removed. If a polyp bulges into a mushroom shape, it can be cut at its base with a lasso-like tool in a procedure called a polypectomy. When a polyp is flat, it’s scooped out in pieces with biopsy forceps.

As a person with FAP ages, the number of polyps increases. By age 30, if not sooner, the colon should be removed through a surgery known as a colectomy. A variety of approaches can be used, depending on the number of polyps present. “We often try to leave a segment of the rectum or to make a pouch of small intestine, so that patients don’t require an ostomy bag,” Vilar-Sanchez said.

With the colon removed, the risk of colorectal cancer becomes almost none. “This effectively prevents FAP patients from dying of colorectal cancer,” Vilar-Sanchez says.

Duodenum disease remains a concern

Even when the colon is removed, polyps can still form in the remaining gastrointestinal tissue. Many patients later develop cancer in their duodenum, which is the first part of the small intestine.

Although a Whipple procedure would remove the duodenum, the impacts on quality of life as well as the risks of the surgery can be challenging. “It’s a difficult surgery,” Vilar-Sanchez says. “It’s life-changing.”

The anti-inflammatory drug sulindac can serve as a chemoprevention therapy as an alternative approach to managing polyps in the duodenum.

“The problem is that it’s a lifelong intervention, and it stops working after some time,” Vilar-Sanchez says. To improve efficacy, combinations with sulindac can be tried, including with the targeted therapy erlotinib or difluoromethylornithine (DFMO for short).

But Vilar-Sanchez hopes for more. “It’s the most challenging situation in the field right now,” he says.

Clinical trials aim to discover new method for duodenum disease prevention

“The picture is changing, thanks to clinical trials,” Vilar-Sanchez says. He is currently leading several clinical trials that aim to manage the risk of cancer in patients with FAP without compromising quality of life.

One clinical trial is studying obeticholic acid (Ocaliva), an FDA-approved oral drug that acts as a synthetic bile acid to stops pathways of intestinal stem cells. Because the medication is already approved for patients with primary biliary cirrhosis, there’s a good amount of data proving the safety of the drug and its effects, Vilar-Sanchez says. Along with his team, he’s investigating if obeticholic acid can serve as a chemoprevention therapy to slow or halt the development of polyps in the duodenum of patients with FAP who have received a colectomy.

“We’re hoping to see a modulation of growths of polyps in the upper and lower intestine,” Vilar-Sanchez says.

Paying it forward for future generations

Many patients participating in clinical trials do it knowing they’re helping future patients. Patients with FAP experience that on a much more personal level since their children, and even their children’s children, will likely face the diagnosis.

“By participating in these types of trials, patients are changing the landscape for their families and future generations,” Vilar-Sanchez says. “For them, it’s personal.”

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