1. McGraw, Mark

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A new multicenter study led by Johns Hopkins researchers found that surveillance programs for patients at high risk of developing pancreatic cancer can help detect precancerous conditions and cancer early (J Clin Oncol 2022; doi: 10.1200/JCO.22.00298). The research also noted the deadliness of pancreatic cancer, which is projected to become the second most common cause of cancer death in the U.S. within the next decade (JAMA Netw Open 2021; doi:10.1001/jamanetworkopen.2021.4708).

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The authors pointed out that, while pancreatic cancer survival "has improved modestly in recent years" to approach 11 percent, the overall 5-year survival rate is still "poor" and can be largely attributed to the late stage of diagnosis for most patients. "In particular," the researchers wrote, "very few patients are diagnosed with Stage I pancreatic ductal adenocarcinoma (PDAC)."


However, they added that the percentage of patients diagnosed with Stage I PDAC has been increasing in the U.S. in the past decade, which may be due to a number of factors, including improvements in diagnostic imaging, better access to care leading to earlier diagnosis of symptomatic disease (Stage I PDAC diagnosis associated with having better insurance coverage), and the enrollment of more at-risk individuals (with familial/genetic risk and/or incidentally detected pancreatic cysts) into pancreatic surveillance programs.


Against this backdrop, the team of researchers sought to report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of the Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.


Study Details

For the study, individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between the years 2014 and 2021. The primary endpoint was the stage distribution of PDAC detected-Stage I versus higher stage. The Kaplan-Meier method was used to determine overall survival.


Of the 1,461 high-risk individuals enrolled into CAPS5, 48.5 percent had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance.


Of the remaining nine patients, seven (77.8%) had Stage I PDAC (by surgical pathology) detected during surveillance; one had Stage II, and one had Stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions. Three had high-grade and five had low-grade dysplasia in their resected specimens.


In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9 percent of whom had Stage I and 5.2 percent had Stage IV disease, according to the authors. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were Stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3 percent, and median overall survival is 9.8 years compared with 1.5 years for patients diagnosed with PDAC outside surveillance. Overall, the investigators determined that most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had Stage I disease with long-term survival.


The U.S. Preventive Services Task Force does not currently recommend screening for pancreatic cancer, noted Anne Marie Lennon, MBBCh, PhD, Professor of Medicine and Director of Gastroenterology and Hepatology at Johns Hopkins Medicine and a co-author of the study.


"One of the major reasons for this recommendation is the lack of evidence to support screening. The major impetus for this study was to answer this question: Can screening detect early, curable, pancreatic cancer, which is associated with long-term survival?" she noted.


Lennon added that the hypothesis for the study was that screening individuals at high risk for pancreatic cancer can detect lesions at a stage where they are still curable. Ultimately, this research demonstrated that the screening modalities Lennon and her colleagues used-endoscopic ultrasound and MRI-were able to detect small lesions when they are curable.


"The study shows that it is possible to screen high-risk individuals for pancreatic cancer and to detect an early curable cancer," she stated. "This supports the CAPS guidelines, which recommend screening for high-risk individuals."


The ability to identify cancers at a much earlier stage is likely due to the surveillance program and the proficiency of the professionals reviewing the MRIs and performing the endoscopic ultrasound procedures, added study co-author Linda Lee, MD, FACG, FASGE, Medical Director of Endoscopy at Brigham and Women's Hospital.


"Endoscopic ultrasound is highly dependent upon the skill of the endosonographer and requires a gastroenterologist specifically trained and experienced in this procedure," stated Lee, who is also Associate Professor of Medicine at Harvard Medical School. "As mentioned in the [study], the case mix of having fewer patients carrying a specific mutation (CDKN2A), which is associated with more aggressive disease, likely also contributes to the positive findings in this patient population."


While noting that further study is needed, with longer-term follow-up of these patients as well as a larger population of patients who developed pancreatic cancer, "these results suggest that enrolling patients at high risk for pancreatic cancer in a surveillance program at an expert center can benefit them by detecting lesions earlier when they are more treatable," Lee concluded.


Mark McGraw is a contributing writer.