Detecting early pancreatic cancer: problems and prospects

Abstract

Pancreatic cancer has a poor prognosis. Improving survival will require diagnosis of early pancreatic cancer, which can be defined based on resectability, size, or curability. Pancreatic cancer progresses from noninvasive precursor lesions to invasive cancer over a variable time period. Retrospective review of computed tomography (CT) scans performed prior to diagnosis suggests that pancreatic cancer resectability may be significantly improved if detected as few as 6 months before clinical diagnosis. Since pancreatic cancer is relatively uncommon, to allow cost-effective screening the populations will have to be enriched for the disease using two "sieves." The first sieve would identify a population of subjects at higher than average risk of pancreatic cancer and the second sieve could be a characteristic phenotype among the members of the high-risk group, an abnormality seen on noninvasive imaging or a serologic marker of early pancreatic cancer. So far two high-risk groups have been targets of screening for pancreatic cancer: hereditary pancreatic cancer kindreds and new-onset diabetes. There is no serologic marker of early pancreatic cancer. Confirmation of diagnosis usually requires invasive procedures such as endoscopic ultrasonography (EUS). Although much work still needs to be done, the developments in the field provide us with hope that screening for early pancreatic cancer could become a reality in the not-so-distant future.

Figure 1

“Early” Pancreatic Cancer- Definitions

Figure 2

Model of Histologic and Radiologic Progression of Pancreatic Cancer

Figure 3

Can’t win them all! This 59 year old woman had a CT on 4/27/2005 (A) for post cholecystectomy pain which even on retrospective review shows a normal pancreas. Four months later, a repeat CT (B) done for continued narcotic requiring pain locally advanced pancreatic cancer confirmed by biopsy.

Figure 4

This shows the pancreas cuts on yearly CTs done for surveillance on this patient with history of colon and endometrial cancer. The pancreas on the CT in 1994 (A) appeared entirely normal. In 1995 the pancreas showed a hint of a visible (but not abnormal) pancreatic duct with slight glandular atrophy (B). However, these findings were considered within normal limits. Comparison of the CT in 1996 (C) with earlier CTs suggested further dilatation of the pancreatic duct and led to the performance of EUS (inset) which revealed a 2 cm mass in the body of the pancreas. Patient was asymptomatic. Resection of the mass confirmed the diagnosis of T1N0M0 ductal adenocarcinoma. Patient is alive 9 years later despite developing ureteral cancer in the interim. She was subsequently shown to carry a mutation in the mLH1 gene confirming the suspicion of HNPCC.

Figure 5

Step-wise Approach to Screening for Pancreatic Cancer