In the Clinic: Challenges in Pancreatic Cancer Screening

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There are many challenges to developing the most effective screening modality for pancreatic cancer.
There are many challenges to developing the most effective screening modality for pancreatic cancer.

Pancreatic cancer is one of the most feared diagnoses, partly because it is the fourth leading cause of cancer-related deaths in men and women in the United States.1 It is projected that by 2020, pancreatic cancer may become the second leading cause of cancer-related deaths.2

Diagnosing pancreatic cancer can be particularly challenging because patients typically do not develop symptoms until the cancer has become more invasive. Only between 10% to 20% of patients at time of diagnosis carry a stage that is conducive to surgical resection and potential cure.3 Additionally, patients with pancreatic cancer only have a 5-year survival rate of 6%.2 Ideally, clinicians would be able to diagnose pancreatic cancer earlier in order to offer patients better treatment options and decrease morbidity and mortality. However, there are many challenges to developing the most effective screening modality for pancreatic cancer.

Pancreatic cancer is diagnosed in 3 types of clinical scenarios: sporadic (90%), familial (7%), and inherited cancer syndromes (3%).2 The overall incidence is relatively low, affecting approximately 10 out of every 100 000 people.2 Therefore it would not be clinically or cost-effective to screen the entire population. The “typical” symptoms associated with pancreatic cancer, including painless jaundice and significant weight loss, usually do not develop until the cancer is advanced. Consequently, many patients with early pancreatic cancer are asymptomatic or have non-specific symptoms.

Imaging tests such as computed tomography and magnetic resonance imaging do not have the ability to detect all pancreatic lesions concerning for malignancy, especially those that are small. Endoscopic techniques such as endoscopic ultrasound and endoscopic retrograde cholangiopancreatography represent innovative techniques increasingly used to diagnose pancreatic cancer, however the best algorithm on when and how to use these procedures has not been determined.

CA 19.9 is the most frequently used biomarker associated with pancreatic cancer, however its main use is for monitoring patients either during or after treatment (chemotherapy and/or surgery). An elevated CA 19.9 level is not entirely diagnostic of pancreatic cancer, as many concurrent medical conditions can increase CA 19.9, including biliary obstruction, cholangitis, cirrhosis, pancreatitis, and other malignancies.2 Most studies have reported a sensitivity and specificity of CA 19.9 of approximately 80%.2 Other biomarkers being developed and studied including carcinoembryonic antigen, heat shock protein 27, carcinoembryonic antigen-related cell adhesion molecule 1, adenosine deaminase, matrix metallopeptidase 7, and osteopontin.3 Although none of these biomarkers are more sensitive or specific than CA 19.9, there are ongoing studies evaluating the use of several biomarkers at the same time to improve accuracy.

Most major societies do not recommend screening for pancreatic cancer in average-risk patients based on its relatively low incidence. This includes the Unites States Preventive Services Task Force, which recommends against routine screening for pancreatic cancer in asymptomatic patients.

However, this recommendation was made in 2004. There is growing evidence to support pancreatic cancer screening in patients that are considered “high risk.” The exact definition of a high-risk patient eligible for screening is somewhat variable; however several studies have suggested screening patients with Peutz-Jeghers Syndrome, hereditary pancreatitis, certain gene mutations (BRCA1/2, p16, MLH1, MSH2, MSH6 or PMS2) and > 1 first degree relative (FDR) with pancreatic cancer or > 3 first, second, or third degree relatives with pancreatic cancer of which there is > 1 FDR.4,5

In addition to there not being a consensus on the exact subset of patients to screen, the specific age or imaging/endoscopic test of choice has yet to be fully established.

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29.
  2. Chari ST, Hollingsworth KK, Thayer SP, et al. Early detection of sporadic pancreatic cancer: summative review. Pancreas. 2015;44(5):639-712.
  3. Poruk KE, Firpo MA, Adler DG, Mulvihill SJ. Screening for pancreatic cancer: why, how, and who? Ann Surg. 2013;257(1):17-26.
  4. Canto MI,  Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339-347.
  5. Grover S, Syngal S. Hereditary pancreatic cancer. Gastroenterology. 2010;139(4):1076-1080.

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