ORLANDO – A novel urinary test differentiates pancreatic cancer from chronic pancreatitis and could ultimately provide a tool for the early detection of pancreatic cancer, according to findings from a prospective multicenter study in Germany.
In an independent validation cohort of 47 patients with pancreatic cancer and 60 patients with chronic pancreatitis, the test – which measures the distribution of 55 peptides shown in a screening cohort to be distinct in malignant vs. benign disease – had an area under the curve (AUC) of 0.89. At the optimum cutoff, sensitivity and specificity of the test were 85% and 91%, respectively, Dr. Bastian Schönemeier reported at the annual Digestive Disease Week.
In 94 healthy controls, specificity was 80%, he said, explaining that the test was designed to compare malignant and benign disease, rather than malignant disease and no disease.
The use of proteomic analysis to identify patterns of multiple peptide markers that may have diagnostic value is an emerging technology that has shown promise in other conditions, as well. For example, Dr. Schönemeier and his colleagues demonstrated in a prior study that a proteomic analysis of urine distinguishes cholangiocarcinoma from other benign biliary disorders.
Given their success, the investigators began to investigate whether certain peptide markers in urine are differentially regulated in pancreatic cancer and chronic pancreatitis. The goal was include the most discriminative peptides in a multimarker model for accurate differentiation of the two conditions.
Peptides with altered excretion levels in a sample of 18 patients with histologically proven, but untreated pancreatic cancer, and 22 patients with chronic pancreatitis were identified using capillary electrophoresis coupled online to mass spectrometry. Those that differed significantly between the groups were included in the model, which was then applied prospectively to the independent cohort and healthy controls.
On amino acid sequencing, fragments of fetuin-a and alpha-1-antitrypsin were among 13 prominent markers for pancreatic cancer. This was verified by enzyme immunoassay and immunohistochemistry.
The findings are intriguing, because the diagnosis of pancreatic cancer – the fifth-most-deadly cancer worldwide, has doubled in incidence during the last 40 years, from 5 to 10 cases per 100,000 persons per year, Dr. Schönemeier said, adding that 5-year survival is less than 5%, because a lack of markers and specific symptoms impedes early diagnosis.
While the urinary test evaluated in this study is promising and clearly is capable of differentiating chronic pancreatitis and pancreatic cancer, further study is needed, he said.
"I’m not saying at all that we can now detect (pancreatic) cancer early, but ... it may be useful for proving pancreatic cancer in unclear cases, and it may be useful for surveillance of patients with chronic pancreatitis, he said.
Longitudinal and larger studies are needed to verify the findings, he noted.
Dr. Schönemeier reported having no disclosures.