Patients with pancreatic cancer are notoriously diagnosed at a late stage and with advanced disease because of a lack of early warning signs and symptoms associated with the disease. And because of these late diagnoses, many patients do not do well; 5-year survival rates are staggeringly low. This paradigm means that efforts to improve screening and surveillance efforts that lead to earlier detection of more cases of pancreatic cancer could greatly benefit patients. In a recent editorial published in the Journal of Clinical Oncology (JCO), Matthew B. Yurgelun, MD, Senior Physician at Dana-Farber Cancer Institute, reviewed two large-scale studies that analyzed prospective data investigating imaging-based pancreatic ductal adenocarcinoma surveillance in individuals with high genetic and familial risk (2022; doi: 10.1200/JCO.22.01287).
The first study published earlier this year, also in JCO, looked at the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants in CDKN2A (2022; doi: 10.1200/JCO.22.00194). The data came from the Leiden University Medical Center Pancreatic Ductal Adenocarcinoma surveillance program in the Netherlands. The researchers concluded that surveillance in the high-risk population led to detection of early-stage pancreatic ductal adenocarcinoma with improved resectability and survival.
The second study reported data from the pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5); it was also published online ahead of print in JCO earlier this year (2022; doi: 10.1200/JCO.22.00298). Those individuals were considered high risk because they met the criteria outlined in the recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. The researchers concluded that the majority of patients diagnosed with pancreatic ductal adenocarcinoma while under this pancreas surveillance have Stage I disease and can achieve long-term survival; median survival for patients in the program diagnosed with the cancer was 9.8 years. And it's worth noting that the predominance of Stage I disease is in marked contrast to more advanced stage cancers of the majority of patients who present with symptomatic pancreatic cancer. In an interview with Oncology Times, Yurgelun shared the learnings from those reports.
1 In this editorial, you reviewed data from two long-term studies on surveillance for pancreatic ductal adenocarcinoma. What were the takeaways that were most important?
"To me, the most noteworthy pieces are that: 1) early pancreatic cancer detection is possible with aggressive imaging-based surveillance, and 2) early detection seems to translate into far better likelihood of cure than what we expect from historical control data. Imaging-based pancreatic cancer surveillance is not new, but until these studies (with long-term follow-up data), it was not clear whether or not early detection of pancreatic cancer truly led to better long-term outcomes, or if these people with pancreatic cancer had bad outcomes regardless of how early it was found."
2 You mention in the editorial that most current guidelines call for screening for individuals who both carry mutations associated with pancreatic ductal adenocarcinoma and have a family history of the cancer. Does this new data suggest that approach is no longer the right one (in terms of that family history piece)?
"I would not say that I'm in favor of dropping the family history piece. I would say that we don't know whether or not we should drop the family history piece. Using family history to triage who does/does not get pancreatic cancer surveillance ultimately restricts the pool of 'eligible' individuals by quite a lot. On the other hand, doing such surveillance in all individuals with inherited genetic risk factors above a certain age would potentially overwhelm the system.
"This is particularly important since the screening itself (and interpretation of the imaging-based screening tests) is extremely nuanced, and expanding this further and wider may shift the risk-to-benefit ratio in an unfavorable direction."
3 Let's talk about access to this type of care and cancer surveillance. Is it possible to increase screening and surveillance capacity if indeed more people would benefit from it?
"I'm convinced that high-quality imaging-based pancreatic cancer surveillance is reasonable to achieve on a large scale. These two studies are great examples of how well this surveillance can work when done in high-volume centers with experienced experts performing, interpreting, and overseeing such surveillance. I think this now needs to be rigorously studied in more 'real-world' settings to know if and how to expand such screening further and wider.
"The bottom-line message is that early pancreatic cancer detection is indeed possible in genetically high-risk individuals, and in many cases such early detection can truly change outcomes for the better. There is still a lot of work to do to figure out how to expand this further and wider, but these are important data that lay the foundation for where we need to go from here."