ASCO GI Interview Series: Improving Patient Outcomes in Pancreatic Cancer: A Conversation with Mitchell C. Posner, MD

Few cancers have a bleaker outlook than pancreatic cancer. The 5-year survival rate hovers at around 5%, according to the American Cancer Society. But ongoing trends in research and clinical care offer reason for optimism that this outlook will improve. Overcoming the pessimism and clinical nihilism surrounding pancreatic cancer is the first challenge toward achievement of better outcomes, according to Mitchell C. Posner, MD, an oncologic surgeon at the University of Chicago. During the Gastrointestinal Cancers Symposium, Posner shared his thoughts on the current state of research and clinical care for pancreatic cancer, as well as his thoughts about the potential to improve patient outcomes.

OBTN: In general, the prognosis for pancreatic cancer remains poor. Can you point to any bright spots that might offer hope for better outcomes in the future?

Dr. Posner: Oh, definitely. I think there has been a lot of focus, from the patient's perspective and that of doctors, to ensure that patients get to high-volume institutions, where they will see surgeons who are very experienced in pancreatic resection. Since pancreatic resection is the only potentially curative measure, I think that's a plus. I think you can see that patients, in fact, are going to high-volume centers, and that's a good thing. Clearly, the mortality from surgery been reduced to 2% or less, which I think is remarkable.

However, we still don't cure [very many] people with surgery. We know there is adjuvant therapy that has value. The question is how do you build on that? There are studies going on to try to unravel that dilemma. There are trials looking at preoperative therapy, which I think is something that has the potential to be a difference maker, primarily in the fact that if we can eventually have more access to a patient's tissue before treatment and after treatment, we'll answer a lot more questions than we have in the past.

Of course, people are looking at new targeted agents. People are looking at ways of affecting not only the cancer cell but the surrounding environment the cancer cell sits in, to try and enhance therapy.

I think all of those things are exciting. Is there a home run in there? No, but I think a single in this game is a big hit.

Given that surgery remains the only potentially curative therapy for pancreatic cancer, early diagnosis is a given if a patient is to have a realistic chance at long-term outcome. Unresectable disease is universally fatal. Has any progress been made toward identifying potential risk factors for pancreatic cancer? For example, have any genetic traits or other markers been identified that could lead to earlier diagnosis or at least identify patients who have an increased risk and might benefit from close follow-up?

There was a discussion session and several abstracts related to cystic neoplasms, which we think are precursors to pancreatic cancer or premalignant conditions. By getting a better understanding of these lesions, we might be able to identify patients who require surgery and might derive a lot of benefit from surgery. Studying these cystic neoplasms might also help us identify the patients who are going to "cross the line," so to speak, and develop a full-blown cancer. The lesions might have certain characteristics or undergo certain changes that provide an early indication about the subsequent course the condition might take. There is a lot of effort being devoted to determining which patients should have surgery and which patients should be followed.

Everyone is always looking [to] predict a patient's risk or to find a mechanism to identify patients who are at risk, and therefore give us an opportunity to intervene earlier. The best way to treat a cancer is to prevent a cancer, especially this one.

At one of this meeting's principal sessions on pancreatic cancer, all of the abstracts presented revolved around efforts to predict what will happen to patients after treatment or to identify patients who might be a higher or lower risk. What is the significance of that? Does that reflect the current most active area of research in pancreatic cancer?

The fact is that everyone with pancreatic cancer is high risk. All you have to do is look at the incidence and mortality, and when they match up, everyone is at high risk. A lot of the research is trying to identify more effective therapy that is along the lines of more targeted agents, as opposed to classic chemotherapy, which has been the focus of much clinical research in the past. There is a lot of interest in looking at potential biomarkers to be able to predict who will benefit from a certain treatment, and if the patient isn't likely to benefit, he or she can be switched to something else that might give them a better chance.

Every pancreatic cancer patient should be preferentially treated in a clinical trial. No one is doing that well. There are a number of avenues of research that constitute a continuum, from trying to determine genetic markers, predicting response to treatment, predicting who might be likely to benefit from additional treatment after surgery, or [predicting] who will respond to a specific treatment.

In your estimation, were there any studies reported at this meeting that stood out because of the results or because of the innovative strategy reflected in the work?

I think it would be difficult to single out any particular studies. As I said earlier, ongoing research represents a continuum. In this particular clinical arena, I think that doing relatively small studies--in terms of the number of patients--and not focusing on just one avenue but looking at many different avenues at the same time is the way to go. That approach is in evidence at this meeting. That's what people are trying to do. Some people are looking at stem cells. Others are looking at stroma where the cells sit and how to affect that to deliver therapy better. Others are looking at specific pathways to attack. I don't see any one of these studies or approaches turning into a breakthrough or a difference maker. My guess is that a combination of these lines of research will eventually make a difference, not a single magic bullet.

Looking at the work that is going on now and in the past, I can't point to one specific study or even one area of investigation and say, "Wow, that's the most exciting thing I've seen in the past 10 years." We always get fooled by doing that. I think that pursuing several avenues of investigation, and not letting a single patient get by without enrolling in a clinical trial that is trying to answer a specific question about this disease that is so lethal, is the way to go.

At your own institution, what is the standard of care for patients who have resectable pancreatic cancer?

For patients who are deemed resectable, we have a current national trial that is run through the American College of Surgeons Oncology Group. It involves giving preoperative treatment: preoperative chemotherapy with a targeted agent. Then the patient has surgery and receives additional treatment afterward. Ideally, if a patient fits the enrollment criteria, we put the patient in that trial.

For patients who don't meet the criteria for that trial, there is an open Radiation Therapy Oncology Group trial, evaluating adjuvant therapy and addressing the question of whether radiation therapy adds anything to adjuvant chemotherapy. That has always been an open question, at least in some people's minds.

If patients are borderline resectable at the outset, I think at our institution we tend to individualize treatment. For patients who can tolerate it, we tend to give preoperative chemotherapy, followed by surgery. It's an individual decision, though.

Every patient who comes to us wants to have the cancer out tomorrow. One of the challenges is to convince patients that snatching out the tumor [does not prevent] anything, and try to educate them that the statistics show that even if we take out the tumor, the likelihood is that it will come back. Convincing patients to take a different approach to looking at the disease is really key.

Are there any messages about the ongoing research or current standards of care for the nonspecialist or nononcologist, who often will be the first clinician to come in contact with a patient who has pancreatic cancer?

As you said, they are the first line of defense against this disease. Obviously, [clinicians should be alert to] any patients who develop any symptoms suggestive of pancreatic cancer: weight loss, changes in the color of the skin, early signs of obstructive jaundice. Although by then they usually have a fairly large tumor.

I think the key is partnering with a group of people who more frequently treat these patients. A study reported several years ago showed that a considerable number of patients with resectable pancreatic cancers were not being referred to surgeons. I think primary care physicians have a nihilistic view that there is nothing that can be done. [I would agree that] we are not curing [very many] patients. However, we can prolong patients' lives. I think the quality of life after a pancreatic resection is quite good nowadays. If I marched in a group of patients who had undergone the procedure, I doubt that they would look any different from you and me. They lead very normal lives.

The value of linkage can't be overestimated. Getting rid of that pessimistic view, trying to explore different approaches to treatment, [and] sending patients to places where we can begin to answer questions [are crucial]. At the same time, people who specialize in treating pancreatic cancer have to work with the primary care physicians who are going to [be] caring for the patients, in addition to us.

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Charles Bankhead is a freelance medical writer in Houston, Texas. He has written extensively about oncology and regularly covers major national and international oncology conferences.

Published in Oncology & Biotech News. February 2011.