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Pancreas Cancer

Pancreatic cancer is a very common cancer, and it goes from 9^th to 4^th when you start looking at death rates, 27,000 cases and only a 5% five-year survival. But in the background here we have to remember there is some reason for optimism. There is improved diagnostics, we are beginning to understand this disease at a molecular level, like colon cancer. There have been improved surgical outcomes and I might touch on this later. Actually from the 1970’s to now there has been a statistically, albeit small, improvement.

However, again, the overall survival is still measured in months. Ninety percent of patients come to us with pain and weight loss. With resectable pancreatic cancer we have some chance with stage I disease, perhaps 25% cure rate, but we only see 10% of patients at that stage. So clearly, early diagnosis would be desirable in this disease. Do we have the tools to do that now? And ultimately I think it’s a very equivocal maybe. So this shows what’s happened to the survival rates at Hopkins.

So we have clearly seen an improvement in the outcome of resectable pancreatic cancer. It’s arguable. Is this really a shift in the biology of the disease, or is it earlier diagnosis? I don’t think anybody is really sure. Now this on the other hand, of course, is the curve for advanced or metastatic cancer and you can see that we really look at 50% survival measured in 5-6 months, and this shows the curve GEM, gemcitabine therapy. Again, node negative resectable pancreatic cancer, maybe 40% five-year survival.

But as we all know, small pancreatic cancer may not be early pancreatic cancer. This is a study from Japan that looked at 106 patients from multiple centers who had a cancer under 2 cm. At that time, 30% of them already had lymph node metastases, 14% had stage III or IV disease, and of the patients with stage I pancreatic cancer confined to the pancreas, 30% died of recurrence. So in some patients this is a very aggressive systemic disease at the time of presentation.

What about the epidemiology? Well, the incidence doubled from 1930 -1970, but it sort of stabilized at about 8 per 1000. We have very few clues really to guide us in our clinical management. The environmental risks include smoking - about a two-fold rise - chronic pancreatitis which will talk about later, diabetes is probably a cause from the pancreatic cancer.

So what about management? For resectable disease it’s surgery and adjuvant chemo-radiation. Locally unresectable disease, we would argue for radiation and 5-FU and for metastatic, gemcitabine. Why radiation therapy? Well, this again is the Hopkins data. We have similar uncontrolled studies that show that if you follow up surgery with radiation therapy that those patients definitely have improved survival. That was shown at least in one randomized controlled trial, the so-called GITS study.

So let’s talk first about imaging studies, and we have come a long way, since this is a slide from a retired colleague showing a pancreatic cancer going into the bowel on a contrast radiograph of the small intestine. Clearly the test of choice today is a dual phase CT scan, on a helical scanner. This shows the first phase and it looks like a fairly normal … you start to get a suggestion of perhaps something here, but then in the parenchymal phase on this helical CT the mass is quite readily apparent. So this has really become the standard imaging test of choice. It also detects metastatic disease.

What about amylin? It’s an eyelet-related peptide. This is increased particularly in pancreatic cancer associated with diabetes, but not in diabetics without pancreatic cancer. The idea is that this amylin which induces an insulin-resistant state is actually the cause of pancreatic cancer- induced diabetes. How common is that association? Well, if you look, it’s been known for a long time that there’s an association between diabetes and pancreatic cancer and depending on how hard you look, if you just go by history, 20% but if you actually look at biochemical studies you can see that two-thirds to three-fourths of patients.

In summary, most patients presenting with pancreatic cancer are at an advanced stage. They will be eligible for palliative care only. I would argue that helical CT is the test of choice. EUS is certainly promising and has a clinical role in selected patients. We are currently engaged in a trial looking at helical CT versus EUS versus MRI in the diagnosis. I think ERCP is rarely needed. Tumor markers are inappropriate for screening, obviously. Their routine clinical use I think is very limited. The one thing about CA 19-9, which you are probably all aware of, the higher the level the more diagnostic it is. But there are case reports of levels in the hundreds of thousands due to benign disease.

Management, except for the few patients with very early cancer, management is very inadequate. Traditional approaches are unlikely to have an impact, and we really need a paradigm shift in the treatment strategy for this disease. I think, hopefully, genetic manipulation or immune therapy.