Screening for Pancreatic Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Objective: We conducted a systematic evidence review to support the U.S. Preventive Services Task Force (USPSTF) in updating their recommendation on screening for pancreatic cancer. Our review addresses the following Key Questions (KQs):
1. Does screening for pancreatic adenocarcinoma improve cancer morbidity or mortality or all-cause mortality; and 1a) Does screening effectiveness vary by clinically relevant subpopulations (e.g., by age group, family history of pancreatic cancer, personal history of new-onset diabetes, or other risk factors)?
2. What is the diagnostic accuracy of screening tests for pancreatic adenocarcinoma?
3. What are the harms of screening for pancreatic adenocarcinoma?
4. Does treatment of screen-detected or asymptomatic pancreatic adenocarcinoma improve cancer mortality, all-cause mortality, or quality of life?
5. What are the harms of treatment of screen-detected pancreatic adenocarcinoma?
Data Sources: We searched Cochrane Central Register of Controlled Trials, Medline, and PubMed, and reference lists of relevant systematic reviews. We searched for articles published from 2002 to October 3, 2017, and updated our search on April 27, 2018. We also searched ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP), for relevant ongoing studies.
Study Selection: We reviewed 19,596 abstracts and 824 articles against specified inclusion criteria. Eligible studies included those written in English and conducted in adults age 18 years or older with or without risk factors for pancreatic cancer. For key questions on screening, we included imaging-based screening protocols. For key questions on treatment, we included studies of adults with screen-detected or asymptomatic pancreatic adenocarcinoma.

Data Analysis: We conducted dual, independent critical appraisal of all provisionally included studies and abstracted study details and results from fair- and good-quality studies. Because of the limited number of studies and the population heterogeneity, we provided a narrative synthesis of results and used summary tables to allow for comparisons across studies. After confirming that the yield of different imaging modalities was similar across studies, we calculated a pooled diagnostic yield across studies and produced forest plots to illustrate the range of effects seen across studies. For harms of screening (KQ3) and harms of treatment (KQ5), we stratified results by procedural and psychosocial harms.
Results: We included 13 unique prospective cohort screening studies (24 articles) reporting results for 1,317 people. Studies were conducted in the U.S., Canada, and Europe, and all screening populations except one small comparison group were exclusively in persons at elevated familial or genetic risk for pancreatic cancer. No studies reported on the effect of screening for pancreatic adenocarcinoma on cancer morbidity, mortality, or all-cause mortality (KQ1); and no studies reported on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma (KQ4).

Thirteen fair quality studies reported on the diagnostic accuracy of screening tests for pancreatic adenocarcinoma (KQ2). Across these studies, 18 cases of pancreatic adenocarcinoma were detected.. Twelve of 18 cases (66.7%) were detected at stage I or II or classified as “resectable.” Pooled yield for all screening tests to detect pancreatic adenocarcinoma on initial screening in high-risk populations was 7.8 per 1000 (95% confidence interval, 3.6 to 14.7); and for total yield including both initial and repeat screening, it was 15.6 per 1000 (95% CI, 9.3 to 24.5).

Harms of screening for pancreatic adenocarcinoma
Procedural harms of screening were evaluated in eight screening studies (n=675); psychological harms were assessed in two studies (n=277). Details on the assessment of harms were variably reported. In two studies (n=277) in which 150 individuals received ERCP as a diagnostic followup test, 15 people (10%) reported acute pancreatitis, nine of which required hospitalization. No evidence of increased worry, distress, depression, or anxiety after screening was reported, compared to before screening.

Harms of treatment of screen-detected pancreatic adenocarcinoma
Of the 57 people who underwent surgery across all studies, six studies (n=32 people receiving surgery) assessed harms of treatment of screen-detected pancreatic adenocarcinoma (KQ5), with 7 harms detected in two studies. Methods of assessing harms were variably reported. Harms included one person experiencing stricture to the hepaticojejunal anastomosis at 11 months after surgery, one with unspecified post-operative complications, 2 with post-operative fistula and 3 cases of diabetes. In the two studies that systematically assessed harms in all surgical patients (n=12 people receiving surgery), no harms were reported.

Limitations: No randomized trials of screening were identified. The body of evidence includes observational screening studies with limited sample sizes and focused on populations with known familial risk, many with a substantial proportion of people with known genetic mutations. No studies included a clinical followup or unscreened comparison group, limiting assessment of diagnostic accuracy. Of those studies that reported harms of screening or treatment, limitations included inadequate description of the methods of assessing harms, including whether all participants were systematically assessed.

Conclusions: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the clinical impact of screening is not well documented. There is insufficient evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.