Draft Recommendation Statement
Pancreatic Cancer: Screening
This opportunity for public comment expired on March 4, 2019 at 8:00 PM EST
Note: This is a Draft Recommendation Statement. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Recommendation Statement will be developed after careful consideration of the feedback received and will include both the Research Plan and Evidence Review as a basis.
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decisionmaking to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Pancreatic ductal adenocarcinoma (referred to hereafter as pancreatic cancer) is an uncommon cancer with an age-adjusted annual incidence of 12.6 cases per 100,000 person-years. However, the death rate is 10.9 deaths per 100,000 person-years because the prognosis of pancreatic cancer is poor.1 Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. The overall 5-year survival rate for pancreatic cancer is 8.5%.1 Surgical intervention at an early stage is the treatment most likely to improve survival, although even with resection, the median survival for early, stage I pancreatic cancer is 36 months.2 Currently, most cases of pancreatic cancer are detected at an advanced stage,1 when surgical resection is not likely to be beneficial. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second leading cause of cancer death in the United States.3
In 2018, an estimated 55,440 persons were diagnosed with pancreatic cancer and 44,330 persons died of it.1 About 85% to 90% of persons diagnosed with pancreatic cancer do not have known familial risk or genetic syndromes, 5% to 10% of persons have familial risk, and 3% to 5% of cases are due to inherited genetic cancer syndromes (such as Peutz-Jeghers syndrome). Familial pancreatic cancer is defined as a kindred with at least two affected first-degree relatives; a person’s degree of familial risk depends on the number of affected relatives.4-6
In 2004, the USPSTF reviewed the evidence on screening for pancreatic cancer in asymptomatic adults and issued a D recommendation. The USPSTF has decided to use a reaffirmation deliberation process to update this recommendation. The USPSTF uses the reaffirmation process for existing A or D grade recommendations for which only a very high level of evidence would justify a change in the grade of the recommendation. In its deliberation of the evidence, the USPSTF considers whether the new evidence is of sufficient strength and quality to change its previous conclusions about the evidence.
The USPSTF found no evidence on the accuracy of imaging-based screening tests (computed tomography [CT] scan, magnetic resonance imaging [MRI], or endoscopic ultrasonography [EUS]) for pancreatic cancer.
Benefits of Detection and Early Treatment
The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. Based on the low incidence of pancreatic cancer in the general population, the uncertain accuracy of current candidate screening tests, and the poor prognosis for pancreatic cancer even when treated at an early stage, the USPSTF found adequate evidence to bound the benefits of screening for pancreatic cancer in asymptomatic adults as no greater than small.
Harms of Detection and Early Treatment
The USPSTF found adequate indirect evidence to bound the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer as at least moderate, based on potential harms from false-positive results and the harms of treatment.
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.
Draft: Clinical Considerations
Patient Population Under Consideration
This recommendation applies to asymptomatic adults not known to be at high risk of pancreatic cancer. Therefore, this recommendation does not apply to persons at high risk of pancreatic cancer due to having an inherited genetic syndrome known to be associated with high risk of pancreatic cancer (e.g., Peutz-Jeghers syndrome, hereditary pancreatitis) or due to a history of familial pancreatic cancer.
Assessment of Risk
Persons with certain inherited genetic syndromes or a history of familial pancreatic cancer are at high risk of pancreatic cancer. This recommendation does not apply to these high-risk populations.
Other factors such as new-onset diabetes, pre-existing diabetes, older age, cigarette smoking, obesity, or a history of chronic pancreatitis increase risk to a lesser degree. The USPSTF considers persons who may have these other risk factors part of the general population, and they are included in this recommendation.
The USPSTF does not recommend screening for pancreatic cancer in the general population using any method. Imaging-based methods, such as the CT scan, MRI, and EUS, have been studied as screening tests in trials of screening persons at high risk of pancreatic cancer due to inherited genetic syndromes or familial pancreatic cancer. There are currently no accurate, validated biomarkers for early detection of pancreatic cancer.2, 7-11
Treatment or Interventions
Surgery (pancreaticoduodenectomy [Whipple procedure] or total or distal pancreatectomy) is the generally recommended treatment for pancreatic cancer that is deemed to be resectable at the time of diagnosis. Neoadjuvant or adjuvant chemotherapy may be recommended, depending on the stage of cancer and other factors.
Draft: Other Considerations
Research Needs and Gaps
Research is needed to develop effective screening tests with high sensitivity and high specificity for pancreatic cancer and, ideally, high-grade precursor lesions. Research is needed to better understand the prevalence and natural history of precursor lesions to pancreatic cancer, and the likelihood of precursor lesions progressing to pancreatic cancer.
Studies investigating the benefits and harms of screening for pancreatic cancer in persons at high risk due to a history of familial pancreatic cancer and inherited genetic syndromes are an active area of research. Continued research in this area is needed to identify effective screening strategies and to determine the benefits (i.e., improved clinical outcomes) and harms of screening for pancreatic cancer in this population. If a net benefit of screening is found in high-risk persons, studies of screening in persons who may be at increased risk (e.g., adults with new-onset diabetes) may be warranted.
Last, pancreatectomy carries a significant risk of morbidity and mortality, and the prognosis for more advanced pancreatic cancer, which is not amenable to surgery, is poor. Research on better treatments for all stages of pancreatic cancer to improve long-term survival and decrease the harms of treatment is needed.
Burden of Disease
Pancreatic cancer is uncommon, with an estimated incidence of 12.6 cases per 100,000 person-years. It has a poor prognosis, with an overall 5-year survival rate of 8.5%.1 Surgical intervention at an early stage is the treatment most likely to improve survival, although even with resection, the median survival for stage I pancreatic cancer is 36 months.2 Currently, most cases of pancreatic cancer are detected at an advanced stage,1 when surgery is not likely to improve the survival rate. In 2018, an estimated 55,440 persons were diagnosed with pancreatic cancer, and 44,330 persons died of it, making it the third most common cause of cancer death in the United States.1
Scope of Review
To update its 2004 recommendation on screening for pancreatic cancer, the USPSTF commissioned a systematic review on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer.12 The USPSTF considered studies of screening in persons at high risk of pancreatic cancer due to familial history to determine whether this evidence might help inform its recommendation on screening for pancreatic cancer in the general population.
Accuracy of Screening Tests
The USPSTF found no studies that reported on the sensitivity or specificity of CT scan, MRI, or EUS as screening tests for pancreatic cancer.
The USPSTF found 13 cohort studies of screening for pancreatic cancer, mostly in persons at high familial risk, using CT scan, MRI, or EUS (n=1,317) that reported on the yield of screening.13-25 One study also included screening in a group of 161 participants who did not have known familial or genetic risks, and detected no cases of pancreatic cancer in this group.21 Among high-risk participants in all studies, a total of 18 cases of pancreatic cancer were found across all rounds of screening, for a yield of 15.6 cases per 1,000 persons.12 The applicability of these data to persons not at high risk of pancreatic cancer is uncertain, and the yield of screening in a population with a lower incidence of pancreatic cancer is likely to be much lower. Another important consideration is that any screening test used in a population with a lower incidence of pancreatic cancer would potentially have a lower positive predictive value and a higher rate of false positives.
Effectiveness of Early Detection and Treatment
The USPSTF found no studies on the benefits of screening for pancreatic cancer or on the benefits of treatment of screen-detected or asymptomatic pancreatic cancer in the general population.
In the 13 cohort studies of screening in persons at high familial risk, a total of 57 screened patients underwent pancreatic surgery. Of the 57 patients undergoing surgery, 14 were found to have pancreatic cancer, 38 had precursor lesions (intraductal papillary mucinous neoplasm, pancreatic intraepithelial neoplasia, or both), and five had neuroendocrine tumors, liver hyperplasia, or a benign serous cystadenoma.12 Because the risk of progression of precursor lesions (particularly low-grade lesions) to invasive cancer is not clear, the balance of the potential benefits or harms of detecting and undergoing pancreatic surgery to remove such lesions is unknown. Pancreatic intraepithelial neoplasia is common, and most cases do not progress to cancer. In two studies, 26% to 54% of pancreata removed at surgery for reasons other than pancreatic cancer contained such lesions.26, 27 These data suggest the possibility that screening in the general population might lead to overdiagnosis.
In the screening studies of high-risk persons, a total of 18 cases of pancreatic cancer were detected. As noted above, 14 of these cases were confirmed by surgery. An additional four cases were detected at an advanced stage and had nonresectable disease. Twelve of the cases (66.7%) were detected at stage I or II or were classified as “resectable.”12 Data on health outcomes were limited due to inconsistent reporting of follow-up data for detected cases. The USPSTF did not find studies that compared health outcomes for screened and unscreened populations to determine the effectiveness of screening. Additionally, the applicability of these results to a population not at high risk is uncertain.
Potential Harms of Early Detection and Treatment
The USPSTF reviewed 10 cohort studies of screening for pancreatic cancer in high-risk persons to assess the potential harms of screening and treatment. In two studies (n=271) that assessed the psychosocial harms of screening, the majority of participants reported normal levels of distress or worry at all time points.28, 29 One study reported no change in levels of perceived pancreatic cancer risk, worry, and general distress at baseline and 3 months postscreening,28 while a second study reported Cancer Worry Scale scores that decreased over time (compared to baseline scores).29
Eight studies reported on procedure-related harms of screening.13, 14, 16-21 In one study of 216 persons who underwent EUS, 55 (25.5%) reported mild postprocedure pain, and 13 (6.0%) reported adverse events related to anesthesia.21 Of 150 persons in two studies who underwent endoscopic retrograde cholangiopancreatography as a diagnostic test, 15 (10.0%) developed acute pancreatitis, nine of whom required hospitalization.20, 21 The remaining six studies identified no harms related to screening.13, 14, 16-19 The prevalence of incidental findings was not consistently reported in the available studies.
Six studies reported on the harms of surgery.13, 16, 17, 19, 21, 30 One study reported a stricture to the hepaticojejunal anastomosis in one patient 11 months after surgery and unspecified postoperative complications in another patient.13 In another study, two cases of postoperative fistula and three cases of diabetes were reported.16 Four studies reported no harms.17, 19, 21, 30
Pancreatectomy carries a significant risk of morbidity and mortality, and additional data on the harms of surgery are available from studies that were not specifically conducted in screen-detected persons. A German study of 428 patients undergoing pancreatectomy (primarily pancreaticoduodenectomy) reported a 33.6% rate of any complication.31 One 2003 U.S. study reported a 4.6% rate of perioperative mortality after pancreatectomy for neoplastic disease,32 and another U.S. study of 21,482 pancreatectomies performed between 2007 and 2010 found a 3.7% 30-day mortality rate.33
Estimate of Magnitude of Net Benefit
The USPSTF considered the evidence using a reaffirmation process and found no new evidence on the benefits of screening for pancreatic cancer. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. Therefore, the USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms.
Draft: Reaffirmation of Previous USPSTF Recommendation
This recommendation is a reaffirmation of the USPSTF 2004 recommendation statement against screening for pancreatic cancer in asymptomatic adults.34 In 2004, the USPSTF reviewed the evidence on screening for pancreatic cancer and concluded that the harms of screening for pancreatic cancer exceed any potential benefits. For the current recommendation, the USPSTF commissioned a systematic review12 to look for new evidence on the benefits and harms of screening. The USPSTF found no new substantial evidence that would change its recommendation and therefore reaffirms its recommendation against screening for pancreatic cancer in asymptomatic adults.
Draft: Recommendations of Others
No organization currently recommends screening for pancreatic cancer in the general population of asymptomatic adults. The American College of Gastroenterology conditionally recommends surveillance for pancreatic cancer in certain high-risk persons (e.g., those with known genetic syndromes associated with pancreatic cancer and those from familial pancreatic cancer kindreds who have an affected first-degree relative), and suggests that surveillance should be performed in experienced centers, ideally under research conditions.35
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3. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913-2921.
4. Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg. 2010;44:293-311.
5. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388(10039):73-85.
6. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51(1):14-24.
7. Chang JC, Kundranda M. Novel diagnostic and predictive biomarkers in pancreatic adenocarcinoma. Int J Mol Sci. 2017;18(3).
8. Loosen SH, Neumann UP, Trautwein C, Roderburg C, Luedde T. Current and future biomarkers for pancreatic adenocarcinoma. Tumour Biol. 2017;39(6):1010428317692231.
9. Choe JW, Kim JS, Kim HJ, et al. Value of early check-up of carbohydrate antigen 19-9 levels for pancreatic cancer screening in asymptomatic new-onset diabetic patients. Pancreas. 2016;45(5):730-734.
10. Dumstrei K, Chen H, Brenner H. A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection. Oncotarget. 2016;7(10):11151-11164.
11. Herreros-Villanueva M, Bujanda L. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have. Ann Transl Med. 2016;4(7):134.
12. Henrikson NB, Aiello Bowles EJ, Blasi PR, et al. Screening for Pancreatic Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 181. AHRQ Publication No. 19-05250-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2019.
13. Joergensen MT, Gerdes AM, Sorensen J, Schaffalitzky de Muckadell O, Mortensen MB. Is screening for pancreatic cancer in high-risk groups cost-effective? Experience from a Danish national screening program. Pancreatology. 2016;16(4):584-592.
14. Harinck F, Konings I, Kluijt I, et al; Dutch research group on pancreatic cancer surveillance in high-risk individuals. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut. 2016;65(9):1505-1513.
15. Al-Sukhni W, Borgida A, Rothenmund H, et al. Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg. 2012;16(4):771-783.
16. Schneider R, Slater EP, Sina M, et al. German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Fam Cancer. 2011;10(2):323-330.
17. Verna EC, Hwang C, Stevens PD, et al. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res. 2010;16(20):5028-5037.
18. Ludwig E, Olson SH, Bayuga S, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol. 2011;106(5):946-954.
19. Poley JW, Kluijt I, Gouma DJ, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol. 2009;104(9):2175-2181.
20. Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2(7):606-621.
21. Canto MI, Goggins M, Hruban RH, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006;4(6):766-781.
22. Shin EJ, Topazian M, Goggins MG, et al. Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study. Gastrointest Endosc. 2015;82(5):812-818.
23. Del Chiaro M, Verbeke CS, Kartalis N, et al. Short-term results of a magnetic resonance imaging-based Swedish screening program for individuals at risk for pancreatic cancer. JAMA Surg. 2015;150(6):512-518.
24. Barnes CA, Krzywda E, Lahiff S, et al. Development of a high risk pancreatic screening clinic using 3.0 T MRI. Fam Cancer. 2018;17(1):101-111.
25. Gangi A, Malafa M, Klapman J. Endoscopic ultrasound-based pancreatic cancer screening of high-risk individuals: a prospective observational trial. Pancreas. 2018;47(5):586-591.
26. Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol. 2003;16(10):996-1006.
27. Konstantinidis IT, Vinuela EF, Tang LH, et al. Incidentally discovered pancreatic intraepithelial neoplasia: what is its clinical significance? Ann Surg Oncol. 2013;20(11):3643-3647.
28. Maheu C, Vodermaier A, Rothenmund H, et al. Pancreatic cancer risk counselling and screening: impact on perceived risk and psychological functioning. Familial Cancer. 2010;9(4):617-624.
29. Konings IC, Sidharta GN, Harinck F, et al. Repeated participation in pancreatic cancer surveillance by high-risk individuals imposes low psychological burden. Psychooncology. 2016;25(8):971-978.
30. Canto MI, Hruban RH, Fishman EK, et al; American Cancer of the Pancreas Screening (CAPS) Consortium. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012;142(4):796-804.
31. Kamphues C, Bova R, Schricke D, et al. Postoperative complications deteriorate long-term outcome in pancreatic cancer patients. Ann Surg Oncol. 2012;19(3):856-863.
32. McPhee JT, Hill JS, Whalen GF, et al. Perioperative mortality for pancreatectomy; a national perspective. Ann Surg. 2007;246(2):246-253.
33. Swanson SR, Pezzi CM, Mallin K, Loomis AM, Winchester DP. The 90-day mortality after pancreatectomy is double the 30-day mortality: more than 20,000 resections from the National Cancer Data Base. Ann Surg Oncol. 2014;21(13):4059-4067.
34. U.S. Preventive Services Task Force. Screening for Pancreatic Cancer: U.S. Preventive Services Task Force Recommendation Statement. Rockville, MD: Agency for Healthcare Research and Quality; 2004.
35. Syngal S, Brand RE, Church JM, et al; American College of Gastroenterology. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223-262.
Internet Citation: Draft Recommendation Statement: Pancreatic Cancer: Screening. U.S. Preventive Services Task Force. February 2019.