Perspective

USPSTF maintains stance against pancreatic cancer screening in asymptomatic adults

Chyke A. Doubeni, MD, MPH
Chyke A. Doubeni

Adults without family history, signs or symptoms of pancreatic cancer should not be screened for the disease, according to a draft recommendation issued by the U.S. Preventive Services Task Force.

Tests for pancreatic cancer have limited accuracy and can be invasive, sometimes leading to pain, false-positive results, adverse reactions to anesthesia and pancreatitis.

“We need more research in this area. We don’t have good screenings [for pancreatic cancer], and we don’t have good treatments,” Chyke A. Doubeni, MD, MPH, USPSTF member and presidential professor and associate professor of epidemiology at Perelman School of Medicine at University of Pennsylvania, told HemOnc Today. “You have to screen a lot of people to find pancreatic cancer and, even if you find it early, the outcomes usually aren’t great.”

The task force based the D recommendation — consistent with previous USPSTF guidelines — on a review of 13 unique prospective studies on pancreatic cancer screening that included results for 1,317 people aged 18 years and older with or without risk factors for the disease.

“Using a reaffirmation deliberation process, the USPSTF concludes that there is no new evidence that warrants a change in the prior D recommendation and reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms,” the USPSTF recommendation statement reads.

Uncommon but deadly

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, according to the statement.

The American Cancer Society estimates that in 2019, about 56,770 people in the U.S. will be diagnosed with pancreatic cancer 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 survival of 36 months.

However, more than 80% of cases are detected in advanced stages, when it is too late for surgery. The 5-year OS rate for those patients ranges from 2% to 5%, compared with 8.5% overall.

Data from the SEER database and National Cancer Database show median survival for patients with pancreatic cancer who underwent surgery ranged from 15 to 27 months, compared with 3 to 8 months for patients who did not undergo surgery.

Another challenge in detecting pancreatic cancer is its symptoms, which are common in other diseases and can include jaundice, vomiting, pain and weight fluctuation.

“Detecting the disease is very difficult. I compare it to ovarian cancer ... it takes a lot for a mass to show up,” Doubeni said. “These symptoms are nonspecific, so you can’t really just narrow them down to the pancreas right away. And because [the disease] is rare, you sometimes don’t catch it quickly.”

There are several established risk factors for pancreatic cancer.

About 5% to 10% of cases occur among relatives with no genetic mutations. Another 3% to 5% of cases are due to inherited genetic mutations, such as STK11/LKB1, CDKN2A/p16, BRCA1, BRCA2, PRSS1, SP1NK1, CTFR, MLH1, MSH2, MSH6, PMS2 and ATM.

People of Ashkenazi Jewish heritage or with hereditary chronic pancreatitis also are at a higher risk of developing pancreatic cancer.

Other risk factors include diabetes, tobacco use, chronic pancreatic cancer and obesity.

Screening tools, limitations

The report on the systematic evidence review for the USPSTF lists several image-based screening tests — including endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, MRI, magnetic resonance cholangiopancreatography, abdominal ultrasonography and CT — used to detect pancreatic cancer, as well as their limitations.

Although there are no validated biomarkers for early detection of pancreatic cancer, the report includes several potential candidates, including CA 19-9. However, its limited sensitivity and specificity has restricted its usefulness.

Carcinoembryonic antigen, or CEA, is another potential single-biomarker test cited in the report, in addition to micro-RNA patterns from circulating exosomes, hypermethylation of specific genes in circulating DNA and detection of circulating tumor cells.

“Multiple-biomarker panels may have the highest potential as a noninvasive screening test for pancreatic adenocarcinoma, given the heterogeneity of tumor types and the limited accuracy of any single biomarker,” the report states.

Results, potential harms

Of the 1,317 people screened for pancreatic cancer across the 13 studies reviewed, a total of 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 1 or stage 2 and deemed resectable.

Fifteen patients 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 harms related to screening. Six of these studies identified no harms related to screening procedures.

One study found 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, nine of whom required hospitalization.

Two studies that evaluated psychosocial harms of screening found 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.

Tumors other then adenocarcinoma were excluded because of their distinct etiologies.

“Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma and its precursor lesions with limited evidence of minimal harms,” the report states. “However, the impact of screening on morbidity and mortality in groups at high familial risk is not well documented, nor is the impact of screening in other groups at risk for pancreatic adenocarcinoma due to other behavioral or clinical risk factors. There is insufficient evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.”

THE USPSTF is accepting public comment on the draft recommendation through March 4 at www.uspreventiveservicestaskforce.org/tfcomment.htm. – by John DeRosier

For more information:

Chyke A. Doubeni , MD, MPH, can be reached at Perelman School of Medicine at University of Pennsylvania, 1st Floor, 3930 Chestnut St., Philadelphia, PA, 19104; email: chyke.doubeni@uphs.upenn.edu

Disclosures: Doubeni reports no relevant financial disclosures. Please see the report for all other authors’ relevant financial disclosures.

Chyke A. Doubeni, MD, MPH
Chyke A. Doubeni

Adults without family history, signs or symptoms of pancreatic cancer should not be screened for the disease, according to a draft recommendation issued by the U.S. Preventive Services Task Force.

Tests for pancreatic cancer have limited accuracy and can be invasive, sometimes leading to pain, false-positive results, adverse reactions to anesthesia and pancreatitis.

“We need more research in this area. We don’t have good screenings [for pancreatic cancer], and we don’t have good treatments,” Chyke A. Doubeni, MD, MPH, USPSTF member and presidential professor and associate professor of epidemiology at Perelman School of Medicine at University of Pennsylvania, told HemOnc Today. “You have to screen a lot of people to find pancreatic cancer and, even if you find it early, the outcomes usually aren’t great.”

The task force based the D recommendation — consistent with previous USPSTF guidelines — on a review of 13 unique prospective studies on pancreatic cancer screening that included results for 1,317 people aged 18 years and older with or without risk factors for the disease.

“Using a reaffirmation deliberation process, the USPSTF concludes that there is no new evidence that warrants a change in the prior D recommendation and reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms,” the USPSTF recommendation statement reads.

Uncommon but deadly

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, according to the statement.

The American Cancer Society estimates that in 2019, about 56,770 people in the U.S. will be diagnosed with pancreatic cancer 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 survival of 36 months.

However, more than 80% of cases are detected in advanced stages, when it is too late for surgery. The 5-year OS rate for those patients ranges from 2% to 5%, compared with 8.5% overall.

Data from the SEER database and National Cancer Database show median survival for patients with pancreatic cancer who underwent surgery ranged from 15 to 27 months, compared with 3 to 8 months for patients who did not undergo surgery.

Another challenge in detecting pancreatic cancer is its symptoms, which are common in other diseases and can include jaundice, vomiting, pain and weight fluctuation.

PAGE BREAK

“Detecting the disease is very difficult. I compare it to ovarian cancer ... it takes a lot for a mass to show up,” Doubeni said. “These symptoms are nonspecific, so you can’t really just narrow them down to the pancreas right away. And because [the disease] is rare, you sometimes don’t catch it quickly.”

There are several established risk factors for pancreatic cancer.

About 5% to 10% of cases occur among relatives with no genetic mutations. Another 3% to 5% of cases are due to inherited genetic mutations, such as STK11/LKB1, CDKN2A/p16, BRCA1, BRCA2, PRSS1, SP1NK1, CTFR, MLH1, MSH2, MSH6, PMS2 and ATM.

People of Ashkenazi Jewish heritage or with hereditary chronic pancreatitis also are at a higher risk of developing pancreatic cancer.

Other risk factors include diabetes, tobacco use, chronic pancreatic cancer and obesity.

Screening tools, limitations

The report on the systematic evidence review for the USPSTF lists several image-based screening tests — including endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, MRI, magnetic resonance cholangiopancreatography, abdominal ultrasonography and CT — used to detect pancreatic cancer, as well as their limitations.

Although there are no validated biomarkers for early detection of pancreatic cancer, the report includes several potential candidates, including CA 19-9. However, its limited sensitivity and specificity has restricted its usefulness.

Carcinoembryonic antigen, or CEA, is another potential single-biomarker test cited in the report, in addition to micro-RNA patterns from circulating exosomes, hypermethylation of specific genes in circulating DNA and detection of circulating tumor cells.

“Multiple-biomarker panels may have the highest potential as a noninvasive screening test for pancreatic adenocarcinoma, given the heterogeneity of tumor types and the limited accuracy of any single biomarker,” the report states.

Results, potential harms

Of the 1,317 people screened for pancreatic cancer across the 13 studies reviewed, a total of 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 1 or stage 2 and deemed resectable.

PAGE BREAK

Fifteen patients 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 harms related to screening. Six of these studies identified no harms related to screening procedures.

One study found 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, nine of whom required hospitalization.

Two studies that evaluated psychosocial harms of screening found 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.

Tumors other then adenocarcinoma were excluded because of their distinct etiologies.

“Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma and its precursor lesions with limited evidence of minimal harms,” the report states. “However, the impact of screening on morbidity and mortality in groups at high familial risk is not well documented, nor is the impact of screening in other groups at risk for pancreatic adenocarcinoma due to other behavioral or clinical risk factors. There is insufficient evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.”

THE USPSTF is accepting public comment on the draft recommendation through March 4 at www.uspreventiveservicestaskforce.org/tfcomment.htm. – by John DeRosier

For more information:

Chyke A. Doubeni , MD, MPH, can be reached at Perelman School of Medicine at University of Pennsylvania, 1st Floor, 3930 Chestnut St., Philadelphia, PA, 19104; email: chyke.doubeni@uphs.upenn.edu

Disclosures: Doubeni reports no relevant financial disclosures. Please see the report for all other authors’ relevant financial disclosures.

    Perspective
    Andrew H. Ko

    Andrew H. Ko

    More than 80% of patients with pancreatic cancer present at advanced stages, at which point cure no longer represents the goal of treatment. An equally if not more sobering reality is that even those individuals whose disease is diagnosed early enough to allow for surgical resection end up recurring the vast majority of the time.

    Thus, despite significant advances in our understanding of the biology of this disease as well as some incremental improvements in systemic therapies, the most significant impact we are likely to make in this disease will occur through improvements in primary prevention, screening and early detection. Diagnosing pancreatic tumors when they are still in precursor stages — such as pancreatic intra-epithelial, or PanIN, lesions or intraductal papillary mucinous neoplasms, or IPMNs — allows the best opportunity for intervention with true curative intent.

    However, to date a population-wide screening tool for pancreatic cancer in asymptomatic, standard-risk individuals — one that meets all the necessary criteria for screening, including being cost-effective, low-risk/minimally invasive, and able to detect disease at early/premalignant stages, as well as having a low false-positive rate — has been elusive. As such, the USPSTF, in its recent draft statement, has reinforced its previous stance recommending against routine pancreatic cancer screening.

    So, where does that leave us?

    First, it should be emphasized that certain groups of individuals, such as those with a strong family history of pancreatic cancer or who are known carriers of certain deleterious mutations (including BRCA2 and PALB2) that predispose them to pancreatic cancer, are reasonable candidates for whom to consider screening. Although the interval frequency and type of screening in such high-risk individuals remains debatable, successful screening programs have traditionally included imaging modalities such as magnetic resonance cholangiopancreatogram, as well as endoscopic ultrasound, sometimes in alternating annual fashion.

    Moreover, newer, less invasive approaches hold promise for the future, including blood- or other body fluid-based methods for detecting tumor-specific nucleic acids — such as circulating tumor DNA and microRNAs — and changes in the microbiome of the gastrointestinal tract or oral cavity represent another intriguing possibility. However, such approaches will require validation in much larger studies before they are ready to be applied routinely in clinical practice.

    Finally, it will be critical to continue educating primary care providers, as well as the public at large, regarding early signs or symptoms of potential concern — sudden-onset diabetes, for example — that may prompt earlier work-up and, at least in some cases, allow for earlier pancreatic cancer detection.

    • Andrew H. Ko, MD
    • HemOnc Today Editorial Board Member
      University of California, San Francisco

    Disclosures: Ko reports no relevant financial disclosures.