Usefulness of novel tumour markers

Most of the successful serological markers used in pancreatic cancer diagnosis detect circulating mucins which are back-secreted into the blood circulation. These markers have sensitivities (70-95%) and specificities (70-95%) which compare well with those achieved by imaging tests yet they have been subjected to very critical review and are still not widely used. There seem to be two main reasons for this: firstly, they are biochemical tests and clinicians tend to expect and demand 100% accuracy for such tests: secondly, the failure of serological tests to prove adequate for screening seems to have deterred clinicians from using them in more appropriate situations. It should have been realised that screening of asymptomatic cases was never going to be achievable until methods could be found for defining a high risk population. With a prevalence of about 10 per 100,000, say 20 per 100,000 adults, a test with 99% specificity (far in excess of that achievable by any current imaging or biochemical tests) would produce 1,000 false positive results for every 20 true positives, a hopelessly unacceptable ratio. In symptomatic patients the odds are very different. The prevalence of pancreatic cancer may be as high as about 15% in patients over 40 years old who have unexplained upper abdominal pain or weight loss and in whom upper G-I endoscopy is negative. In these patients serological tests (with a false positive rate of about 15%) will fare at least as well as imaging tests. Combination of the two modalities i.e. an imaging test such as ultrasound or CT scanning together with a biochemical test such as CA19.9, DuPan2 or CAM17.1 seems both logical and highly practical and has been shown to enhance diagnostic accuracy. The best established pancreatic tumour marker assays all detect mucins. Pancreatic cancers have a particular propensity to secrete mucin into the blood either because of mechanical blockage of the pancreatic duct, loss of polarity of pancreatic cells or early blood vessel invasion. Other mucin secreting cancers e.g. colon and ovary can also cause increased concentrations of the same serological markers albeit less frequently but this is not usually a major cause of confusion since the clinical features are usually distinguishable. Serological markers correlate with tumour staging but are nevertheless still effective in resectable cancer. They may also have a useful role in monitoring after surgical resection or chemotherapy. A serological mucin assay such as CA19.9, CAM17.1, DuPan2 or SPan-1 should be used in conjunction with a scanning test in the diagnosis of patients over 40 with endoscopy-negative abdominal pain, in the investigation of patients with a known pancreatic mass or cyst, and for monitoring following resection or chemotherapy for pancreatic cancer.