Over recent decades good progress has been made in survival for many types of cancer, including breast, colorectal, testicular, and prostate cancers. But some types of malignancies, including pancreatic cancer, have remained resistant to efforts to improve outcomes. Pancreatic cancer has a 5 year relative survival rate of only 6%, a rate that has barely changed over the last 20 years. As the 12th most common cancer in the US, there were an estimated 45,220 new cases of pancreatic cancer in 2013, representing 2.7% of all new cancer cases and 6.6% of all cancer deaths (NCI SEER statistics). Since the symptoms of pancreatic cancer are rather vague - weight loss, loss of appetite and abdominal pain - diagnosis often comes at a very late stage. Because the stage of cancer at diagnosis determines treatment options and strongly influences the length of survival, the earlier pancreatic cancer is caught, the better the outcome is likely to be. However, only 8.7% of pancreatic cancers are diagnosed at the early stage (Stage 1) while still localized without spreading. There are currently no screening methods for the early detection of pancreatic cancer.
Since pancreatic cancer is a relatively rare cancer, there are no well-defined risk groups. An early detection biomarker for people at a normal risk would have to be very accurate in general population screening (>99% specificity and a positive predictive value of >10%) to avoid the many false positives. Positive screening tests would require that patients undergo expensive follow up diagnostic CT scans or biopsies. Furthermore, the screening biomarker would also have to be capable of detecting stage 1 pancreatic cancer or even the neoplastic precursor lesions (PanIN3) to make a difference to survival. Despite these very high hurdles we believe that a ‘do nothing approach’ to pancreatic cancer screening is not acceptable.
At our institution, we are fortunate to have access to a unique prospective biobank of over 5 million serum samples donated by women over a 10 year period. In some cases, we have up to 10 annual samples from the same woman. This biobank is derived from the UK Collaborative Trial in Ovarian Cancer (UKCTOCS), which represents a valuable collection of pre-diagnosis cancer serum samples (for further details see http://www.abcodia.com/serum_bank.php). Some 390 cases of women with pancreatic ductal adenocarcinoma (PDAC) with 597 associated samples were identified in the UKCTOCS cohort and the availability of these samples in the years leading up to diagnosis offers a unique opportunity for discovery and validation of novel biomarkers for the early detection of pancreatic cancer. CA19.9 is the most widely used biomarker as an aid to the clinical diagnosis of pancreatic cancer, but is this marker is not present in about 8% of the population lacking the Lewis A antigen. We demonstrated a longitudinal increase in CA19.9 up to 2 years preceding diagnosis of pancreatic cancer. While CA19.9 used alone may be limited as a screening marker, this data highlighted the utility of changes in CA19.9 over time, combining CA19.9 with other novel biomarkers to predict pancreatic cancer in early stages of disease. How can these early findings be translated into a robust screening test for pancreatic cancer?
References
National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). http://seer.cancer.gov/ Accessed April 15, 2014.
University College of London, Institute for Women’s Health. United Kingdom Collaborative Trial in Ovarian Cancer website. http://www.instituteforwomenshealth.ucl.ac.uk/womens-cancer/gcrc/ukctocs. Accessed April 15, 2014.
Alderton W, Apostolidou S, Flynn A et al. CA19.9 Profiles in Samples Predating Pancreatic Cancer Diagnosis:
A Nested Case Control Study in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). http://www.abcodia.com/docs/aacc_wendy_alderton.pdf. Accessed April 15, 2014.