Bile Duct Cancer – Rare but Numbers are Growing

MD Anderson Cancer Center
Date: 03-12-12

 

[ Background Music ]

Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today our subject is bile duct cancer. And we have 3 guests to talk on that subject today. Our first guest is Dr. Boris Blechacz. He is an assistant professor of gastroenterology, hepatology and nutrition here at MD Anderson. Guest number 2 is Dr. Milind Javle. He is a gastrointestinal medical oncology and associate professor in that department. And also Dr. Thomas Aloia. He is an assistant professor of surgical oncology. Welcome to you, gentlemen. It's going to be a lively discussion, I hope, about cancer. Let's talk first about bile duct cancer as a whole, just the basics. Dr. Blechacz, talk to us about what is bile duct cancer.

Dr. Boris Blechacz: So we basically distinguish a bile duct cancer as the one basically that stem from the bile ducts, the ones from a--which stem from the gallbladder, and the ones that arise from the area of the bile ducts joined basically to the small intestine, the so called ampulla, so ampullary cancers. Our focus here at the moment are the bile duct cancers, at today's talk, and these ones used to be rather rare entity, but due to a significant increase in the US over the last 4 decades, they've actually increased to the point that they are now the most common biliary tract cancers.

Lisa Garvin: Because I--the most statistics I've read or the most recent ones that were about 2 to 3000 diagnosis a year.

Dr. Boris Blechacz: And that has actually increased now. We are on about 4 to 5000. Again, these are the old numbers basically, but now due to the increase in the intrahepatic onset predominantly, we do have significant increase now making it the most common one.

Dr. Milind Javle: So some of this increase may be artifactual, because intrahepatic cholangiocarcinoma, or bile duct cancer within the liver used to be classified in the past as carcinoma unknown primary or one whose source was not known. And these are now being reclassified into this new designation of bile duct cancer, cholangiocarcinoma, and this therefore intrahepatic cholangiocarcinoma is probably one of the most rapidly increasing diagnoses in the western world.

Lisa Garvin: Is it because of reclassification of CUP or are there some environmental risk factors that are weighing in?

Dr. Boris Blechacz: Well, initially was problems of classification actually that were thought that extrahepatic had increased, but then many of these are misclassified. But a review of these numbers have shown that the extrahepatic ones, when we look at the bile duct cancers we also distinguish the ones in the liver and outside the liver. And recent review basically on the numbers have shown that the intrahepatic ones, or the cancers, the bile duct cancers arising within the liver has significant increased by the ones on the extrahepatic bile--biliary tree have remained stable.

Lisa Garvin: Now the most typical patient is many women pretty much equally and generally over 65 and mostly over 70, is that correct?

Dr. Boris Blechacz: That is correct. So predominantly, this is a disease of patients older than 65, very rarely in patients younger than 40. The exception though are patients who have a condition called primary sclerosing cholangitis, who can be diagnosed earlier.

Lisa Garvin: I have had personal experience with this disease. A friend's mother died of it and it seemed that she went downhill extremely fast. From what I understand, you're not catching this before stage 3, in many cases, is that correct?

Dr. Boris Blechacz: Well, that is correct. And that's one of the problems. It's a very clinically silent disease. So until--when patients present at the time when they're already advanced, which makes then, of course, difficult to treat them as a curative intent. So, as you say these are the silent clinical characteristics and the clinical presentation depends on the location of the tumor. Most of the time if they arise within the liver, patients present with unspecific symptoms or incidentally noted to have this mass lesion within the liver. However, patients who have bile duct cancer within the extrahepatic tree, most of the time present with jaundice.

Lisa Garvin: Which is the yellowing of the skin and the eyes.

Dr. Boris Blechacz: Correct.

Lisa Garvin: And also other symptoms I've read is like clay colored stools, appetite and weight loss issues.

Dr. Boris Blechacz: Exactly. The clay colored stool is basically just also manifestation of the jaundice because the bile can't flow anymore into the gut, and the weight loss already is a sign of advanced disease.

Lisa Garvin: And Dr. Aloia, when I was reading up on how they staged this cancer they--there's a basic way of doing it outside the TNM where they say they're either resectable or not resectable. Describe these 2 categories for us.

Dr. Thomas Aloia: Well, I think as the previous physicians have suggested, there really are 2 different kinds of disease. There's the intrahepatic form and the extrahepatic form. And we actually have formal staging systems which apply to both the treatments used by medical oncology and in surgery. So, I really think those 2 things can be taken separately because they have a different approach. It is true that in both settings there can be disease presentations that are immediately unresectable. But actually both settings have options for surgery in some cases, and particularly, in some cases, after treatment with medical therapies when the tumors regress. But the bile ducts are a unique anatomic structure. They're closely associated with the blood vessels that enter and exit the liver. And the most common problem in terms of unresectability is involvement of the vascular structures of the blood vessels that go in the liver. But everyday, we're using complex surgical therapies usually after medical therapies to get margin negative or curative resections in these patients.

Lisa Garvin: Is it hard to image bile duct tumors? Because from what I understand sometimes the extent of the tumor is not known until you're actually in there. Is it hard to image these tumors?

Dr. Thomas Aloia: Traditionally, it has been difficult to image these tumors. MD Anderson uniquely has set the standard for the CT and MRI imaging of the bile ducts. We've written several manuscripts on a CT protocol for bile duct imaging that eliminates, for most patients, that negative laparotomy where you go in and you find more disease than you expected and you have to come out again. So, the imaging is absolutely critical for the surgical treatment planning and it is definitely a shared multidisciplinary review with medical oncology and hepatology and our diagnostic imaging team to try to decide in advance to the best of our ability who is a candidate for resection.

Lisa Garvin: And in your experience here at MD Anderson, percentage wise and baseball park it obviously, how many people are candidates for surgery?

Dr. Thomas Aloia: If you took all the patients that present with this disease, and our center is probably not much different than other major cancer centers, less than 10 percent of patients will present with the disease in a distribution that's resectable. And the main issue is that very early in the course of this disease, patients tend to have spread to their regional lymph nodes and then to other areas of the body. There are issues as you spoke about before with the incidence of the disease as it tends to happen in older patients. The liver resections that are required are usually major liver resections. So that constellation of factors limits the surgical resection options down to probably about 10 percent of patients.

Lisa Garvin: So what about ablative therapy? Is using like heat and/or cold to kill bile duct tumor, is that a viable treatment?

Dr. Thomas Aloia: Typically it isn't. There are 2 kinds of intrahepatic bile duct tumors. There are a mass forming type, which is a ball of tumor cells in the middle of the liver, and then there is a bile duct spreading type, which is along the bile duct. The mass forming type is more amenable to treatments with heat and things like that because it sits more in the middle of the liver. All of the other types of cholangiocarcinoma typically involve the main bile ducts. And any heat generated onto those main bile ducts can 'cause significant complications with bile leaks and things like that. So there is a limited role for that. Our group is exploring options where we deliver either chemotherapy or radiation to these types of tumors through the artery that supplies them, but the heart of treatment of these tumors is systemic chemotherapy.

Lisa Garvin: And Dr. Javle, that's a good segue to you as a medical oncologist. We've gotten a lot of exciting news about chemotherapies in recent years. Are any of those good for bile duct cancer?

Dr. Milind Javle: I would cautiously say yes. It is not a disease that is known to respond tremendously to therapy. But over the last couple of years there has been increasing awareness that a subset of patients do respond to treatment, especially to gemcitabine and cisplatin type of therapy. As was alluded to earlier, not only is this disease diverse in terms of anatomical location, it is very diverse at the genetic level. So, the focus of our group is to see--to assess any possible targeted approaches to this disease. For instance, KRAS, a commonly affected gene in several solid tumors is found to be abnormal 30 percent of the time. So in fact 70 percent of the time, they could be--these patients could be candidates for cetuximab or erlotinib or treatments that are directed to against the EGFR pathway. B-Raf gene that has attracted a lot of attention with the advent of new drugs called MEK inhibitors. This gene is abnormal in about 10 percent of patients with biliary cancer, so there seems to--there's a lot of interest in developing those drugs there. Herceptin, a drug used in breast cancer, is also probably applicable to a small percentage, perhaps, 5 percent of bile duct cancers. So, that's clearly the way forward if we can identify what diverse genetic types exist and then tailor therapy individually to those diversity.

Lisa Garvin:Now, is chemotherapy generally used--it's probably used in adjuvant setting along with other treatment such as surgery, do you use it beforehand to shrink the tumors? Do you use it afterwards to kind of clean up? What is the role of chemo?

Dr. Milind Javle: So, typically, it's used in advanced disease. Most patients 80 percent present with nonoperable tumors. I see between 3 to 5 patients per week, and I would say a vast majority of them are--have advanced inoperable disease. We give them chemotherapy. Rather than as a preface to surgery, we often use that prior to radiation for patients who are not operable. If patients are candidates for surgery, then clearly that would be the preferred modality. And depending on the findings of pathology, we would give chemotherapy or radiation following surgery. For the majority of patients, it's for the treatment of advanced disease.

Lisa Garvin: Well, you talked earlier about multimodal therapy, go into that a little more.

Dr. Milind Javle: The treatment for biliary cancers is very typically involves multiple disciplines. For instance patients get jaundice. They require placement of a biliary stent. In fact, one important cause for mortality in this disease is not just the cancer but infection that occurs secondary to obstruction of the bile duct. So we need services of good GI endoscopies. We need good surgeons at hand to operate either usually before chemotherapy is administered. And then radiation is a common compliment to both surgery as well as chemotherapy. So there are multiple disciplines involved. At MD Anderson, our focus is a multimodality approach towards this disease.

Lisa Garvin: So, truly is a multidisciplinary disease that requires the collaboration across disciplines, it sounds like.

Dr. Milind Javle: Absolutely, and that explains why there's 3 speakers here.

Lisa Garvin: And Dr. Blechacz, are there any symptoms that come up in early stages that people might miss? I mean, is there any way to catch this any earlier?

Dr. Boris Blechacz: Well, I think it depends on the location of the tumor. Number 1, [inaudible] test any condition which predisposes the patient to an advanced risk to develop this kind of cancer. As we talked earlier, the primary sclerosing cholangitis, patients are to increase risk. And here just takes a high level of suspicion of the treating physician, of course. Then again it depends on the location, the stage, and I mean the patients who have what we call periductal or intraductal growing ones or extrahepatic ones. So, where basically the bile can't flow through the bile duct because the tumor compresses the bile duct. But these things might have a chance basically to be diagnosed at an early stage simply because it develops suddenly painless jaundice, for example. So, I think these were the predominant ones. The location is--in such a way that it blocks the bile ducts, number 1, that can result in an early diagnosis, and number 2, it takes also high level suspicion from the physician to diagnose this cancer early.

Lisa Garvin: Dr. Aloia, is a liver transplant an option in for these patients?

Dr. Thomas Aloia: Well, there has been some exciting work done on that area and there certainly appears to be a very small subset of patients who can be treated on a very specific protocol with multiple steps, as we said in the multidisciplinary fashion, starting with chemotherapy and radiation. There's stage with a surgical procedure to confirm that they have early stage disease, and then they can be put on a waiting list for transplant. And that protocol for the patients that go through it successfully has an incredibly good survival. So it's only a small subset of patients are candidates for it, but this is a protocol that we are approved for along with the United Network for Organ Sharing, or UNOS. And there are a number of transplant programs in our region that we partner with if the patient goes through the first 3 steps and has met all the criteria. So I think it's an exciting option. I hope that in the future it can apply to more patients. But right now it's very focused on the early stage patients. But on the flip side those patients tend to do extremely well after the transplant.

Lisa Garvin: Well, as donated organs go, livers are pretty popular. I mean, is it hard to get a liver transplant for cancer patients?

Dr. Thomas Aloia: Typically, on an average basis, it can be difficult. And every--there're several regions in the country and each region is a little different. But for patients that appropriately go through the UNOS approved protocol, they then get advantage on the transplant list. But it's a very specific set of criteria. But if they do meet those criteria and go through all the treatments in the order they're prescribed, they can be advantaged on the list and the average wait time can be as short as 3 months.

Dr. Milind Javle: Tom, what has been your experience in the Houston area regarding liver transplants and availability of donor livers?

Dr. Thomas Aloia: Houston is one of the most competitive regions in the nation for liver transplantation. And each year the number of recipients has outpaced the number of donors, which has been fairly static. So it can be difficult depending on the blood group of the patient to get an organ, but on the UNOS protocol, if patients escalate, which they do every 3 months on the list, the average wait time should be reasonable for an oncologic approach. But again the one part of transplantation, the one factor you can never control is the donor. And so, we're all be holding to that algorithm.

Lisa Garvin: And Dr. Javle, do you see a future in genetic testing like, you know, the BRCA gene is a pretty established gene that we can find in families. Do you foresee the same thing happening in liver cancer, bile duct cancer?

Dr. Milind Javle: Given the rarity of this cancer, I don't see the applicability of such a test in the--on a wider scale. But certain high risk group, as Boris mentioned earlier for instance, cause primary sclerosing cholangitis. Perhaps, while waiting for a transplant, there's probably a rule for screening genetic test in that small population.

Lisa Garvin:And let me get final thoughts from all 3 of you. If you have one message that you wanted to give to patients, what that would be? Dr. Blechacz?

Dr. Boris Blechacz: I think [inaudible] at the moment are an exciting time [inaudible] molecular understanding of the diseases has improved, has a great effort to improve the staging programs in order to [inaudible] of other patients to the better--to the best treatment for them. So I think the prognosis for the disease in the future should become better.

Lisa Garvin: Dr. Javle?

Dr. Milind Javle: The treatment for this disease is complicated, and in my view should be administered in a multidisciplinary fashion at a tertiary cancer center by those with experience. And I can tell you that as a medical oncologist my job for giving chemotherapy becomes infinitely harder if there is no good GI endoscopists to--or interventional radiologist to place biliary stents and [inaudible] the biliary tract.

Lisa Garvin: And Dr. Aloia, your final thoughts?

Dr. Milind Javle: I would agree with Dr. Javle that it's really--this is a rare and unique disease. And even some large centers may not have a significant expertise in this particular thing, particularly with regard to the surgery for this disease, which is fairly and frequently performed outside of a unit that's dedicated to liver surgery. And so, I would say that in the absence of obvious disease that spread far outside the liver to make sure that if a patient is deemed unresectable that that's been reviewed in a multidisciplinary setting with an experienced liver surgeon.

Lisa Garvin: Great. Thank you, all 3 of you. This is a great talk about bile duct cancer. If you have questions about anything you've heard today on Cancer Newsline, contact askMDAnderson at 1-877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.

[ Music ]

© 2012 The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd, Houston, TX 77030
1-800-392-1611 (USA) 1-713-792-6161