UPMC test detects malignant cysts without surgery

Better methods of preventing, diagnosing and treating pancreatic cancer draw welcome fanfare, given that less than 10 percent of all patients survive beyond five years of diagnosis — the worst outcome of all major cancers.

UPMC’s genetic test, Pancre-aSeq, already fueled excitement through nonsurgical identification of molecular biomarkers — genetic mutations — in cyst fluids indicating a higher risk for cancer, allowing for earlier treatment.

Now a recent study shows it also is effective in clinical practice in testing cysts without surgery and removing only those with potential to cause cancer. That means it can prevent unnecessary surgeries to remove cysts with little or no chance of causing cancer and avoid serious surgical side effects.

“This rapid, sensitive test will be useful in guiding physicians on which patients would most benefit from surgery,” Aatur D. Singhi, a surgical pathologist in the UPMC Division of Anatomic Pathology, said in a statement. He was the study’s lead author. “Survival rates for pancreatic cancer are much better if it is caught before symptoms arise, so you also don’t want to ignore early warning signs.”

Medical scans nowadays show many different types of pancreatic cysts — small pockets of fluid in the pancreas. While most are benign, cysts larger than a half inch (or 1.5 centimeters in size), for example, typically pose a higher risk of cancer, he said.

The PancreaSeq test that Dr. Singhi and his UPMC team developed, and is now available for clinical use while it undergoes Food and Drug Administration review, can determine if cyst fluids contain two specific genetic mutations known to raise the risk of cancer.

It then can determine if the fluids also contain a combination of three specific genetic mutations that raise the risk of cancer to 87 percent. Such results raise confidence in removing those cysts responsible for one of the most aggressive forms of pancreatic cancer. Cyst-based

cancers represent about 15 percent of all pancreatic cancers.

Pancreatic cancers are notoriously difficult to diagnose, with most diagnoses occurring in advanced stages, after the cancer has spread. The problem is nonspecific symptoms including diabetes, jaundice, abdominal pain and weight loss, which occur typically in later stages of cancer, Dr. Singhi said.

When people undergo scans for other gastrointestinal ailments, they often reveal pancreatic cysts. Physicians typically look for cysts with certain characteristics that could indicate some risk of cancer. But confirmation required surgical removal of the cysts, which is associated with total medical costs ranging from $40,000 to $100,000. Such surgeries can show no signs of cancer, but lead to death in a small percentage of cases, or such serious side effects as diabetes or pancreatitis, lead to others.

The study, published recently in Gut, the journal of the British Society of Gastroenterology, involved 595 patients, all of whom underwent an endoscope fine-needle aspiration of cysts to recover fluids to be tested with PancreaSeq to see if they contained genetic mutations indicative of cancer.

Funded in part through the Pancreatic Cancer Action Network and National Pancreas Foundation, the study represents the first time the test was conducted in a certified and accredited clinical laboratory rather than in a research setting. That means physicians and patients can use PancreaSeq test results to decide more confidently on a medical course of action.

Of the patients tested, 102 underwent subsequent surgical procedures to remove cysts that bore the genetic mutations of concern. Evaluation of the removed cysts using the PancreaSeq test showed 100 percent accuracy in properly identifying the two specific genes that identify cysts as potentially cancer-causing.

It also was 100-percent successful in identifying three other specific genetic mutations that mean the cyst has a high risk of progressing intopancreatic cancer.

The test, however, was only 30 percent successful in identifying a sub-type of pancreatic cysts called mucinous cystic neoplasms, which involve abnormal tissue growth that can be benign or malignant.

In another important finding, the study revealed no false positives, indicating it is “highly specific” in pin pointing cancerous pathways.

The PancreaSeq test has been available through UPMC for the past two years, with UPMC hospitals now using it routinely to test for cancer in people whose medical scans revealed pancreatic cysts.

Anirban Maitra, scientific director of the Pancreatic Cancer Research Center at the University of Texas MD Anderson Cancer Center, said the mere existence of cysts, often seen in medical scans, has led physicians to perform expensive but unnecessary surgeries with potential side effects.

For that reason, UPMC’s PancreaSeq test is particularly important in preventing unnecessary diagnostic surgeries.

There are dozens of different types of cysts, he said. The two questions they pose are whetherthe cysts are the types associated with pancreatic cancer. Once that is known, the test then can determine a more specific risk of cancer. “[PancreaSeq] does this beautifully,” Dr. Maitra said. He didn’t participate in the study but said he’s familiar with it and interested in the important results.

“To me this is a significant advance,” Dr. Maitra said. “The caveat is that a single institutional study needs to be validated by other studies. But this is very interesting and very exciting, and I’m hoping it will expand in use and become the standard of care in patients.” David Templeton: dtempleton@post-gazette.com or 412-263-1578. Twitter: @Templetoons.