Elsevier

Seminars in Oncology

Volume 34, Issue 4, August 2007, Pages 284-294
Seminars in Oncology

Detecting Early Pancreatic Cancer: Problems and Prospects

https://doi.org/10.1053/j.seminoncol.2007.05.005Get rights and content

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.

Section snippets

Why Is Pancreatic Cancer Mortality so High?

One can identify three main reasons for the dismal prognosis of pancreatic cancer.

Definition(s) of Early Pancreatic Cancer

“Early” pancreatic cancer may be defined based on resectability, size or curability. Here are three definitions in order of decreasing prevalence and increasing survival (Fig 1).

Progression of Pancreatic Cancer From Pre-invasive Precursor to Unresectable Cancer

The now famous Vogelgram of pancreatic cancer proposed by Hruban et al12 plots the histologic and molecular progression of preinvasive stages of pancreatic cancer. However, not much is known about progression of invasive pancreatic cancer. We have tried to recreate, based on published literature, the natural history of pancreatic cancer from its preinvasive stage to its diagnosis and correlate it with symptoms and changes on cross-sectional imaging (Fig 2).

Timeline of Progression From Pre-invasive Precursor to Clinical Diagnosis of Pancreatic Cancer

Pancreatic cancer is frequently unresectable at diagnosis and rapidly fatal once the diagnosis is made. However, the timeline of progression from resectable to unresectable disease is not known. The earliest changes of high-grade dysplasia may appear many years before clinical diagnosis of cancer.16, 17 This is illustrated by the study in which atypical duct lesions preceded the diagnosis of infiltrating adenocarcinoma by 17 months, 9 years, and 10 years in three patients who had previously

Approaches to Screening for Early Pancreatic Cancer

Since sporadic pancreatic cancer patients seldom exhibit disease-specific symptoms until late in the course of the disease, detection of advanced stages of pre-invasive or early invasive pancreatic cancer will require screening asymptomatic patients for the disease. However, pancreatic cancer is relatively uncommon and it would not be cost-effective to screen for it in the general population. In a recent study it was observed that the pretest probability of dysplasia (or cancer) needs to be

Confirming the Diagnosis of Pancreatic Cancer

If noninvasive imaging is equivocal or negative, EUS will be necessary to conclusively diagnose pancreatic cancer. EUS uses high-frequency ultrasound probes placed in the stomach and duodenum juxtaposed to the pancreas, and can identify small pancreatic and periampullary tumors. EUS has exquisite sensitivity to detect tumors as small as 10 mm in size. It also has the capability of providing histologic confirmation of the diagnosis using fine-needle aspiration.60 Thus, the technology now exists

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    Supported by grants from the National Institutes of Health (R01 CA 100685) and the Lustgarten Foundation.

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