Screening May Catch Pancreatic Cancer Early in Those at High Risk

Annual screening of people at high risk for pancreatic ductal adenocarcinoma (PDAC) because of CDKN2A mutations was relatively successful and allowed for the detection of disease in time to perform surgery, according to the results of a study published in the Journal of Clinical Oncology. However, long-term surveillance of people with familial pancreatic cancer yielded less of a benefit.

PDAC has a poor prognosis, but in a small proportion of patients who develop the disease, hereditary factors play a role. Therefore, in this study, the researchers wanted to determine if surveillance of people at high-risk for PDAC could detect early-stage disease or detect precursor lesions (PRLs).

“The current study demonstrated that the resection rate of screen-detected PDAC in CDKN2A/p16-Leiden mutation carriers (75%) was much higher than reported for sporadic PDAC patients (15% to 20%) and for historical controls of CDKN2A/p16-Leiden mutation carriers with symptomatic PDAC (15%),” wrote study authors led by Hans Vasen, MD, PhD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands.

In the study, the researchers collected screening outcomes from 411 participants from three European centers that conduct screening for PDAC in families at high risk. Of these patients, 178 were CDKN2A mutation carriers, 214 had familial pancreatic cancer, and 19 had BRCA1/2 or PALB2 mutations. The surveillance programs consisted of annual MRI, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.

Surveillance revealed that 7.3% of patients with CDKN2A mutations had PDAC, and 75% of these patients underwent resection. PDAC was detected at the first screening for five patients, and eight tumors were detected upon follow-up.

The 5-year survival rate for patients with these mutations was 24% compared with 4% among patients with symptomatic sporadic PDAC.

“One of the most important criteria defined by Wilson and Jungner was that surveillance should improve prognosis,” the researchers noted. “Without a control group, it is difficult to determine with certainty the effects of the surveillance program on PDAC outcome. However, in view of the high resection rate and the better survival compared with the survival rates reported for patients with sporadic PDAC, surveillance of CDKN2A/p16-Leiden carriers complies with this requirement.”

Only two patients (0.9%) with familial pancreatic cancer were found to have pancreatic tumors. Thirteen (6.1%) underwent resection for suspected PRLs, but only four patients had high-risk lesions.

Another four at-risk patients had multifocal grade 2 pancreatic intraepithelial neoplasms (PanINs) and low-grade gastric-type branch duct intraductal papillary mucinous neoplasms (IPMNs) and/or atypical flat lesions. “The question arises of whether multifocal grade 2 PanIN lesions and low-grade IPMNs are also relevant PRLs for PDAC in the setting of [familial pancreatic cancer],” wrote the authors.

In an editorial accompanying the article, Teresa A. Brentnall, of the University of Washington Medical Center in Seattle, noted that these results should affect how clinicians think about screening for pancreatic cancer in several ways.

“First, the data support the idea that earlier detection of pancreatic cancer can significantly improve outcomes. Second, targeting high-risk individuals is one strategy for detecting disease in asymptomatic patients,” Brentnall wrote. “The authors are to be commended for identifying a pathway for earlier detection of pancreatic neoplasia in asymptomatic high-risk patients. These findings emphasize the difficulty in trying to catch PDAC at the highest precancer and the need to keep surveillance at centers of expertise.”