Screening for pancreatic cancer: why, how, and who?

Abstract

Pancreatic cancer is the fourth most common cause of cancer mortality in the United States, with 5-year survival rates for patients with resectable tumors ranging from 15% to 20%. However, most patients presenting with distant metastases, are not resectable, and have a 5-year survival rate of close to 0%. This demonstrates a need for improved screening to identify pancreatic cancer while the tumor is still localized and amenable to surgical resection. Studies of patients with pancreatic tumors incidentally diagnosed demonstrate longer median survival than tumors discovered only when the patient is symptomatic, suggesting that early detection may improve outcome. Recent evidence from genomic sequencing indicates a 15-year interval for genetic progression of pancreatic cancer from initiation to the metastatic stage, suggesting a sufficient window for early detection. Still, many challenges remain in implementing effective screening. Early diagnosis of pancreatic cancer relies on developing screening methodologies with highly sensitive and specific biomarkers and imaging modalities. It also depends on a better understanding of the risk factors and natural history of the disease to accurately identify high-risk groups that would be best served by screening. This review summarizes our current understanding of the biology of pancreatic cancer relevant to methods available for screening. At this time, given the lack of proven benefit in this disease, screening efforts should probably be undertaken in the context of prospective trials.

Figure 1

Stage-dependent survival in 502 patients with pancreatic adenocarcinoma treated at the Huntsman Cancer Institute of the University of Utah. Numbers of patients and median survival in months by stage are given. Stage I patients represent a minority of individuals with this cancer, but their survival is favorable compared to other stages.

Figure 2

Screening programs have potential biases that make demonstration of benefit difficult. In lead-time bias, earlier detection of tumors via screening (scenario A) may appear to result in longer survival than control subjects identified by clinical symptoms (scenario B), however, the natural history of the tumor may not have been altered.

Figure 3

In this schematic, a screening tool has been applied to a hypothetical population of patients at intervals. Each patient is represented by a bar. The length of the bar represents the cancer-related survival of the patient. Length bias refers to the tendency of screening programs to identify patients with tumors with more favorable biology (i.e. slower growth rates or less risk of metastasis) whereas patients with tumors with aggressive biology (rapidly growing tumors or those with a high risk of metastasis) may not be identified because of a short natural history until death. The finding of longer survival in patients identified through screening may not be related to the screening intervention – the benefit could lie in the natural history of those tumors.