Pancreatic Cancer Screening in High-Risk Individuals
August 19, 2019
However, they argue that individuals who have a fivefold increase in relative risk might benefit from surveillance.
These at-risk individuals include those with a family history of pancreatic cancer (specifically, those for whom two or more blood relatives and at least one first-degree relative were affected); those with germline mutations in ATM, BRCA1, BRCA2, CDKN2A, PALB2, PRSS1, STK11, TP53, and the Lynch-syndrome mismatch repair genes; and patients who have been recently diagnosed with new-onset diabetes (which confers an eightfold greater risk).
Timing of surveillance for such people can be guided by the natural history of the disease, Lucas and Kastrinos suggest. For example, even in families with multiple affected relatives, the mean age at diagnosis is 68 years, “which may inform the starting age for surveillance of high-risk individuals,” they write.
In an editorial in JAMA Surgery, Ralph Hruban, MD, of Johns Hopkins School of Medicine, Baltimore, Maryland, and Keith Lillemoe, MD, of Massachussetts General Hospital, Boston, Massachusetts, highlight early results from the Cancer of the Pancreas Screening (CAPS) trial, which were published last year. Hruban was involved in that study.
The CAPS trial followed 354 individuals at high genetic risk for pancreatic cancer for a mean of 5.6 years. In the study, 9 of the 10 pancreatic cancers detected during surveillance were resectable, and 85% of these patients survived 3 years. By contrast, four symptomatic cancers that emerged in patients who were not under surveillance for pancreatic cancer were all unresectable, and only one of these people survived 3 years.
“This is a critical advance because it suggest that down staging, and therefore real benefit, is possible,” Hruban and Lillemoe comment.
Lucas and Kastrinos, in their JAMA editorial, also cite the results of CAPS but acknowledge that the study population extended “beyond the task force’s population of interest.” Although CAPS was not considered by the USPSTF, all 13 cohort studies that were considered were conducted in “persons at high familial risk.”
CAPS may have been published too late to be discussed by the USPSTF. The study results were published in September 2018, 6 months after the USPSTF data search cutoff of April 27, 2018, but within the task force’s ongoing literature surveillance period, which continued until March 22, 2019. The study is listed in the references of the evidence report but is not mentioned in the body of the report.
In their JAMA editorial, Lillemoe and Hruban emphasize the positive. They describe the “extraordinarily bright” future that surveillance offers for individuals at high risk for pancreatic cancer. They say that, despite the rarity of the disease, at-risk people can now be identified and their risk quantified — and that they can be targeted for screening. This has become possible because of such discoveries as the risk-carrying germline variants and the link with new-onset diabetes, they argue. Molecular drivers of the high-grade precancers and early cancers are also now understood and provide targets for early detection technology, they add.
In the third editorial, published in JAMA Internal Medicine, Hruban and colleagues enlarge on promising technologies that could transform the surveillance landscape if validated. For example, studies are being conducted regarding several highly sensitive liquid biopsies for pancreatic tumor DNA and cancer-related protein markers. They also cite a multicenter study of 221 patients in which a multimarker blood test identified 64% of patients with early pancreatic cancer with high specificity.
These editorialist also note that the International Cancer of the Pancreas Screening Consortium has published guidelines for screening high-risk individuals.
JAMA Surg. Published online August 6, 2019. Hruban and Lillemoe editorial
JAMA Intern Med. Published online August 6, 2019. Lennon et al editorial