Surveillance of at least some patients at high risk for pancreatic cancer is “relatively successful” in that it detects most pancreatic ductal adenocarcinomas (PDACs) at a stage when they are still resectable, a report from three expert centers suggests.
The benefit of following families at risk for PDAC is not as evident, the same research shows.
The study was published online April 25, 2016 in the Journal of Clinical Oncology.
These findings “represent a remarkable and encouraging step forward for better management of PDAC, a disease that has not had a significant improvement in survival in the last 50 years,” comments Teresa Brentnall, MD, University of Washington Medical Center, in Seattle, in an accompanying editorial.
Surveillance of Asymptomatic Adults
For the study, lead author Hans Vasen, MD, PhD, from Leiden University Medical Center, the Netherlands, and colleagues followed 411 asymptomatic adults who participated in the surveillance program.
Among these participants, 178 carried the CDKN2A/p16-Leiden mutation, and 19 had either the BRCA1/2 or the PALB2 mutation.
The remaining 214 participants were at risk for familial pancreatic cancer (FPC) by virtue of having two or three first-degree relatives with the malignancy. Hereditary factors contribute to the development of PDAC in about 3% to 5% of all patients, Dr Vasen noted.
The tools used to detect early PDAC or precursor lesions included MRI, magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound. The average age on initiation of surveillance was 48.2 years, and the mean follow-up period for the cohort overall was 2.8 years.
PDAC was detected in 13 individuals among the 178 CDKN2/p16-Leiden carriers; five tumors were detected on the first screening, and eight tumors were detected during follow-up. Nine of these 13 patients were treated with surgery. The remaining four were not treated surgically, either because of the presence of metastases or extensive local disease.
The resection rate of screening-detected PDAC in this group of patients was 75%, and the overall survival rate at 5 years was 24%. Historially, survival rates for patients with symptomatic sporadic PDAC ranges from 4% to 7%, the researchers note.
Surveillance of the same group of CDKN2A/p16-Leiden mutation carriers found precursor lesions in 26 additional patients, two of whom also underwent surgery.
Of the 214 participants at risk for FPC, surveillance detected suspicious lesions in three patients.
Surveillance also detected precursor lesions in 52% of the same at-risk group, and 13 patients of this group underwent surgery to treat the precursor lesion. Suspicious lesions were diagnosed on the first screening in 38.5% of patients and on follow-up visits in the remaining 61.5% of patients.
Only four lesions in the group at risk for FPC were judged to be high riskOf the 13 patients in this at-risk group who were treated surgically, 12 were still alive without any evidence of pancreatic cancer at a median follow-up of 52 months.
Nineteen patients carried either the BRCA1/2 or the PALB2 mutation, but only one patient with a BRCA2 mutation developed PDAC.
Two others underwent surgery because a precursor lesion was detected on surveillance.
Encouraging Step Forward
In her editorial, Dr Brentall described the findings as encouraging and also discussed cost-effectiveness.
She felt that the detection rate for cancerous or precursor lesions of 2% to 7% in the cohort overall was high enough to justify the cost of the surveillance program for individuals at high risk, and even at lower risk, for PDAC.
“To put cancer surveillance for FPC patients in context with other surveillance programs performed in cancer-prone patients, patients with Barrett’s esophagus undergo endoscopic surveillance every 1 to 3 years, and the cancer incidence in this group of patients approximates 1%,” Dr Brentnall told Medscape Medical News.
Similarly, patients with inflammatory bowel disease and chronic colitis undergo fairly frequent colonoscopic surveillance, and in this cohort of patients, the incidence of colon cancer is less than 10%, Dr Brentnall added.
“We have previously performed a cost-effectiveness analysis of pancreatic cancer surveillance in high-risk FPC individuals, and we found that surveillance is cost-effective when the lifetime risk of pancreatic cancer approaches 15%,” she noted, referring to a study published in Gastrointestinal Endoscopy in 2003.
At the least, individuals who are p16-Leiden carriers reach this benchmark of a 15% lifetime risk of PDAC, determined on the basis of genetic penetrance and conferred cancer risk alone, Dr Brentnall pointed out.
Individuals who carry the BRCA1/2 or PALB2 mutation have about a 5% lifetime risk of developing the same cancer, she continued.
“However, the risk [for BRCA1/2 and PALB2 mutation carriers] is amplified by a personal history of smoking, diabetes, and/or the number of family members diagnosed with PDAC,” she said.
For these reasons, most surveillance programs would recommend surveillance for BRCA mutation carriers who have a family history of pancreatic cancer, although BRCA mutation carriers who have no other risk factors may not need surveillance.
Dr Brentnall cautioned that if patients are deemed suitable for surveillance, screening of genetically susceptible individuals needs to be conducted at centers of expertise, for a number of reasons.
“Firstly, management of FPC kindreds is exceedingly difficult, and the stakes are quite high,” she explained.
Interpretation of imaging findings can be operator dependent, particularly in the case of endoscopic ultrasound, she said. In addition, pancreatic surgery has significant attendant morbidity and mortality and also needs to be performed at expert centers.
“I think the success of surveillance programs is based on the multispecialty experience of the team of doctors who care for these high-risk patients,” she said.
“For these very-high-risk patients, knowing when not to operate is just as important as knowing when to operate.”