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USPSTF upholds recommendation against screening for pancreatic cancer
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The U.S. Preventive Services Task Force reaffirmed its stance against pancreatic cancer screening for asymptomatic adults with no family history of the disease.
Members of the task force — who issued draft recommendations in February and left them unchanged after a public comment period — concluded there was no evidence that screening for pancreatic cancer or treatment of screen-detected disease improves mortality or morbidity.
An evidence report and systematic review for the USPSTF — published with the recommendation statement in JAMA, revealed limited evidence to evaluate the benefits and harms of surgery for pancreatic cancer detected through screening.
“Pancreatic cancer is an uncommon but devastating disease with low survival rates, even [among] those detected at early stages,” task force member Chyke Doubeni, MD, MPH, presidential professor and associate professor of epidemiology at Perelman School of Medicine at University of Pennsylvania, said in a press release. “Unfortunately, at the present time, screening for pancreatic cancer in people without any signs or symptoms would cause more harm than good and, therefore, should not be done.”
The task force based the D recommendation — consistent with its 2004 recommendation — on a review of 13 fair-quality prospective cohort studies on pancreatic cancer screening that included results for 1,317 participants aged 18 years and older with or without risk factors for the disease.
Although pancreatic cancer represents a small fraction of cancer diagnoses, is it is the third most common cause of cancer death in the U.S., and soon may become the second leading cause.
The American Cancer Society estimates that about 56,770 people in the United States will be diagnosed with pancreatic cancer this year, and 45,750 will die of the disease.
The treatment most likely to improve survival is surgery at an early stage, which is associated with median OS of 36 months.
However, more than 80% of cases are detected in advanced stages, when it is too late for surgery. Five-year OS rates for those patients range from 2% to 5%, compared with 8.5% overall.
Screening accuracy, harms
Of the 1,317 people screened for pancreatic cancer across the 13 task force-reviewed studies, 57 underwent surgery. They included 14 patients found to have pancreatic cancer; 38 who had precursor lesions removed; and five who had neuroendocrine tumors, liver hyperplasia or benign serous cystadenoma. Four other patients had pancreatic cancer detected at an advanced stage without the use of surgery.
Among the 18 patients (median age, 59.9 years; range, 44-81; 66.7% women) with pancreatic cancer, nine cases were found on initial screening, eight were found on additional screening or during surveillance of abnormal screening results, and one was found at an unknown point. Twelve cases were stage I or stage II and deemed resectable.
Fifteen patients with pancreatic cancer had an average of three people (range, 1-7) in their extended family with the disease, and seven of the patients had a known genetic mutation.
Eight studies involving 675 patients reported procedural harms of screening. Six of these studies identified no harms related to screening procedures.
One study showed that, of 216 people undergoing endoscopic ultrasonography, 55 (25.5%) experienced mild pain and 13 (6%) experienced adverse events related to anesthesia.
Among 150 people across two studies who underwent endoscopic retrograde cholangiopancreatography as an intermediate test, 15 (10%) reported acute pancreatitis and nine of them required hospitalization.
Two studies that evaluated psychosocial harms of screening showed normal levels of distress or worry at all time points among most participants.
The exclusion of people with pancreatic endocrine tumors or exocrine tumors other than adenocarcinoma, as well as the exclusion of biomarker-based screenings, served as limitations of the studies.
“Clinicians need to be able to find pancreatic cancer earlier in its development, when it is more treatable,” Chien-Wen Tseng, MD, MPH, MSEE, USPSTF member and associate research director in the department of family medicine and community health at University of Hawaii John A. Burns School of Medicine, said in a press release. “The task force is calling for more research on effective and accurate screening tests that can detect pancreatic cancer earlier and that lead to fewer harms.”
Hope for the f uture
The oncologic community could have anticipated the recommendation against screening without this comprehensive review, Aimee L. Lucas, MD, MS, associate professor of medicine in the Henry D. Janowitz division of gastroenterology at Icahn School of Medicine at Mount Sinai, and Fay Kastrinos, MD, MPH, assistant professor of medicine at Columbia University Irving Medical Center, wrote in an accompanying editorial.
Approximately 1.6% of people living in the U.S. will develop pancreatic cancer, meaning that even an ideal screening test with 99% sensitivity and 99% specificity would result in 1,000 false positives for every 100,000 patients.
“These false-positive results would require subsequent diagnostic evaluation and accrue additional complications, costs and patient distress that would cause the risks of screening to outweigh any potential benefit,” Lucas and Kastrinos wrote.
However, the D recommendation should not discount advances in the last decade — such as next-generation sequencing — that help identify people at higher risk for pancreatic cancer, they added.
“When a patient is found to carry a germline cancer susceptibility gene, at-risk family members — many of whom may be unaffected by cancer — can be tested for the familial gene. If such a gene is present, those patients may be eligible for pancreatic cancer surveillance,” Lucas and Kastrinos wrote. “This process, known as cascade testing, will undoubtedly increase the pool of newly identified high-risk individuals, as many may have been previously misclassified as at average or moderately increased risk for pancreatic cancer.”
In addition, millions of people are already undergoing screening without knowing it through abdominal CT and MRI scans, Ralph H. Hruban, MD, director of Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University, and Keith D. Lillemoe, MD, chief of surgery at Massachusetts General Hospital, wrote in a separate editorial.
Many radiologists performing these scans may easily miss pancreatic cancer lesions as they focus on the immediate needs of the patient, they added.
“Despite these many potential advances, real progress will not be made unless clinicians in all specialties — primary care, gastroenterology, surgery, pathology and oncology — set aside the generally nihilistic attitude toward the disease and pursue aggressive diagnostic and therapeutic actions,” Hruban and Lillemoe wrote. “Certainly, from a surgical perspective, earlier diagnosis of smaller, less locally advanced tumors offers the opportunity for minimally invasive techniques with or without newer aggressive chemotherapy or exciting new novel therapies, such as immunotherapies.” – by John DeRosier
Disclosures: Doubeni and Tseng report travel reimbursement and honoraria for USPSTF meeting participation. One recommendation statement author reports grants and/or personal fees from Ipsen and Merck. The editorial authors report no relevant financial disclosures.
Perspective
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Anirban Maitra, MBBS
This recommendation was not unexpected, because we believe that pancreatic cancer screening for asymptomatic people in the general population does more harm than good. We do not have the tools — whether they be image-based, blood-based or other biomarkers — to apply this on a broad scale.
This does not mean that screening for pancreatic cancer is not possible. What we have to do is better identify those who need to be screened.
Individuals with a strong family history – which includes two or more family members with pancreatic cancer – and those who have germline mutations themselves are excluded from the USPSTF recommendation. Many academic institutions are screening these high-risk individuals, either under a clinical trial protocol or at a high-risk clinic. Even among this population, we don’t have a consensus on which technique to use or how often to screen. But at least within the general population, this is a piece of the pie that the USPSTF — which is very conservative when it comes to screening for pancreatic cancer — agrees should be excluded from its recommendation.
There are other higher-than-average-risk populations that the task force mentions — including those with new-onset diabetes — that don’t reach the threshold for screening. We know from retrospective publications and prospective data that patients with new-onset diabetes or chronic pancreatitis are at a higher risk for pancreatic cancer. However, the vast majority of these people will not develop pancreatic cancer, and it would be a huge strain on our health care system to screen the 2 million people who have new-onset diabetes each year.
The USPSTF is not a research tool. It is grounded in clinical evidence based on what makes sense at the population level. It is now up to us in the research community to continue working to develop the tools to improve screening practices and justify the screening for patients who are at a higher risk for pancreatic cancer.
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Henrikson NB, et al. JAMA. 2019;doi:10.1001/jama.2019.6190.
Hruban RH and Lillemoe KD. JAMA Surg. 2019;doi:10.1001/jamasurg.2019.2832.
Lucas AL and Kastrinos F. JAMA. 2019;322:407-408.
US Preventive Services Task Force. JAMA. 2019;doi:10.1001/jama.2019.10232.
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