Pancreatic cancer is a ‘silent killer’. It does not like to make itself known. Apple co-founder and former CEO Steve Jobs and Dirty Dancing actor Patrick Swayze both sadly died of pancreatic cancer.Most people suffering from pancreatic cancer don’t realise they have it until it is too late to do anything about it. The five year survival rate after diagnosis is very low indeed, the lowest of any common cancer. Devastating for patients given the diagnosis of pancreatic cancer, the median survival rate is only 5-6 months. This hasn’t changed significantly in decades. Fewer than 20% of patients' tumours are confined to the pancreas at the time of diagnosis. In most cases the malignancy has already progressed to the point where surgical removal is impossible, and surgery, the only viable treatment, stops being an option.
Early diagnosis of pancreatic cancer relies on developing screening methodologies with highly sensitive and specific protein biomarkers, and imaging modalities. That is what makes the recent publication of a urine test for the early diagnosis of pancreatic cancer such exciting news. It leads to the new hope that earlier diagnosis might allow effective treatment, resulting in an improved survival rate. People who are incidentally diagnosed have an improved five-year survival of close to 70%, provided the tumour is small and confined to the pancreas, which it often is when diagnosed early.
How Was This Diagnostic Test Developed?
The first step in developing the diagnostic test was to perform proteomic analysis of urine samples from healthy controls, people with chronic pancreatitis and cancer patients. Early-stage cancer is difficult to differentiate from chronic pancreatitis, so any test for pancreatic cancer would need to be able to separate cancer from pancreatitis, as well as healthy controls. These proteomics experiments were enabled with an Orbitrap-based mass spectrometer (link to MS community page) and led to the identification of three putative protein biomarkers expressed at a high level in the urine of early cancer patients. These preliminary results were then validated in a cohort of nearly 500 urine samples using commercially available quantitative ELISA tests.
How Useful is This Test?
Diagnostic performance was assessed using ROC curve analysis measured in AUCs. Among the analyses performed, the comparison of early-stage cancer with controls was of critical interest. Results of this analysis showed a value of 0.9 AUCs, indicating accurate discrimination of early-stage cancer from healthy controls.
What Next for the Clinical Translational Researchers?
The team intends to look at urine samples collected from volunteers over an extended period of 5-10 years. Some of those volunteers would be expected to develop pancreatic cancer. This longitudinal information will allow the researchers to determine if the panel of 3 biomarker proteins was present during the period after cancer mutations occurred but before the cancer really started to grow. Thus even earlier detection of the pancreatic cancer might be possible. In addition, they hope to carry out further tests from people in high-risk groups of developing pancreatic cancer to validate the existing data.
What is the Outlook for Pancreatic Cancer Patients?
Even though it is still early and this test has not yet been approved for diagnostic use, these results are very encouraging. I would like to quote the final sentence of the paper:
“Being completely noninvasive and inexpensive, this urine screening test could, upon further validation, and when coupled with timely surgical intervention, lead to a much improved outcome in patients with high risk of developing PDAC.”
I should explain that PDAC is Pancreatic Ductal Adenocarcinoma. So the authors of the article are clearly hopeful - even within the confines of academic conservatism - that this work could well lead to longer survival for pancreatic cancer patients. I hope so.
If you would like to read further about this work see Radon et al. Clin Cancer Res 2015; 21:3512-3521.