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Surveillance finds pancreatic ductal carcinoma in situ at resectable stage

Key clinical point: Surveillance of high-risk individuals was relatively successful in detecting pancreatic ductal carcinoma in situ (PDAC) at a resectable stage.

Major finding: The detection rate in CDKN2A mutation carriers was 7.3% and the resection rate for screen-detected PDAC was 75%, compared with previous reports of 15%-20% for symptomatic PDAC; the PDAC detection rate in individuals with familial prostate cancer was much lower at 0.9%.

Data source: Evaluation of an ongoing prospective follow-up study at three European centers included 411 individuals: 178 with CDKN2A mutations, 214 with familial pancreatic cancer, and 19 with BRCA1/2 or PALB2 mutations.

Disclosures: Dr. Vasen and most coauthors reported having no disclosures. Five coauthors reported financial ties to industry sources.

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Progress in earlier detection of pancreatic cancer

Given the difficulty of detecting precursor lesions and distinguishing incipient neoplasia from lower grade or nonneoplastic cystic lesions, the authors of the accompanying study achieved impressive results in improving cancer outcomes among high-risk individuals.

Several strategies for earlier cancer detection can be gleaned from the study. Improved outcomes may depend on expert centers running the surveillance. The detection rate of 2%-7%, depending on the cohort studied and the surveillance protocol, may have room for improvement with better risk stratification and refined protocols for cost effectiveness. The age at the start of surveillance may be one place to start: the mean age of pancreatic ductal carcinoma in situ detection was 53-68 years, depending on the center, and it may be possible to shift the starting age upward to improve yield.

The type of mutation conferring susceptibility may aid in risk stratification. For example, CDKN2A mutation carriers had a higher cancer rate (16%) than BRCA/PALB2 mutation carriers (5%). Other factors that could mitigate risk upward include diabetes, family history, and smoking history. A composite risk assessment could aid in identifying the highest-risk patients. Lastly, future studies are needed to determine which surveillance protocols are best. To make valid comparisons, several surveillance protocols must be tested.

These results impact not only high-risk individuals, but the general population as well. The data support that early detection improves outcomes and highlights the need for developing better biomarkers and tests for early detection of PDAC.

Dr. Teresa A. Brentnall is professor in the department of medicine, division of gastroenterology, University of Washington, Seattle. These remarks were part of an accompanying editorial (J Clin Oncol. 2016 Apr 25. doi: 10.1200/JCO.2015.64.0730).


 

FROM THE JOURNAL OF CLINICAL ONCOLOGY

Surveillance of CDNK2A mutation carriers detected most pancreatic ductal carcinoma in situ (PDAC) at a resectable stage, while the surveillance benefit was lower for those with familial prostate cancer.

Among 178 CDKN2A mutation carriers, PDAC was detected in 13 (7.3%), 9 of whom underwent surgery. Compared with previously reported rates of 15%-20% for symptomatic PDAC, this 70% resection rate represents a substantial increase. The 5-year survival rate of 24% for screen-detected PDAC was higher than 4%-7% reported for symptomatic sporadic PDAC. Among individuals with familial prostate cancer (FPC), 13 of 214 individuals (6.1%) underwent surgery, but with a higher proportion of precursor lesions detected, just four high-risk lesions (1.9% of screened FPC patients) were removed.

Whether surveillance improved prognosis for FPC families was difficult to determine, according to the investigators. The yield of PDAC was low at 0.9%, as was the yield of relevant precursor lesions (grade 3 PanIN and high-grade IPMN) at 1.9%.

“However, if surgical removal of multifocal grade 2 PanIN and multifocal BD-IPMNs is regarded as beneficial, the diagnostic yield increases to 3.7% (eight of 214 patients), and surveillance of FPC might also be considered effective,” wrote Dr. Hans Vasen, professor in the department of gastroenterology and hepatology at the Leiden University Medical Center, the Netherlands, and colleagues. “The value of surveillance of FPC is still not clear, and the main effect seems to be prevention of PDAC by removal of” precursor lesions, they added (J Clin Oncol. 2016 Apr 25. doi: 10.1200/JCO.2015.64.0730).

The retrospective evaluation of an ongoing prospective follow-up study included 411 high-risk individuals: 178 with CDKN2A mutations, 214 with familial pancreatic cancer, and 19 with BRCA1/2 or PALB2 mutations. The study was conducted at three expert centers in Marburg, Germany; Leiden, the Netherlands; and Madrid.

In the BRCA1/2 and PALB2 mutation cohort, one individual (3.8%) with a BRCA2 mutation developed PDAC and underwent surgery; 17 months after the surgery this patient died of liver metastasis. Two others underwent surgery for cystic lesions and are in good health at 10 and 21 months after surgery.

In the cohort of CDKN2A mutation carriers, the mean age at the start of surveillance was 56 years (range, 37-75) and the mean follow-up time was 53 months (range, 0-169): in total, 866 MRIs and 106 endoscopic ultrasounds were conducted. In the FPC group, the mean age was 48 years (range, 27-81), and the mean follow up was 2.8 years (range, 0-10.8): 618 MRIs and 402 endoscopic ultrasounds were conducted. Among BRCA1/2 and PALB2 mutation carriers, the mean age was 52.6 years (range, 25-70), and the mean follow up was 32.7 months (range, 1-119).

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