MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from The University of Texas M.D. 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 guest is Nizar Tannir. He is an Associate Professor of Genitourinary Medical Oncology here at M.D. Anderson and a kidney cancer expert, and kidney cancer is our subject today. Welcome Dr. Tannir.
Nizar M. Tannir, MD, FACP: Good morning. Thank you for inviting me. Thank you for the opportunity.
Lisa Garvin: Let's talk about kidney cancer in general. How many people are generally diagnosed with a form of kidney cancer every year?
Nizar M. Tannir, MD, FACP: In the U.S. it's estimated that about 50,000 people are diagnosed yearly with kidney cancer. About 90% of those cases are what we refer to as renal cell carcinoma and 10% are other tumors that's rarer than this.
Lisa Garvin:: And what does renal cell carcinoma, is that affecting the lining of the kidney or what is it like?
Nizar M. Tannir, MD, FACP: Renal cell carcinoma is not one disease. It's a heterogeneous disease. There are several subtypes of renal cell carcinoma. Usually, the majority of the cases arise from the cortex of the kidney, so it is the outside, the periphery of the kidney. The most frequent type is clear cell renal cell carcinoma or now it was referred to as conventional type renal cell carcinoma. There are some tumor types that are rarer that arise more closely in the central portion of the kidney, but these are the rare forms.
Lisa Garvin: What are the survival rates, you know people have two kidneys, I'm thinking that rarely are both kidneys affected, but are people generally have good survival rates for kidney cancer?
Nizar M. Tannir, MD, FACP:: Well, as is the case with any tumor, survival is dependent on several factors, most importantly is the stage of the disease at the time of the initial diagnosis. So, patients who are diagnosed with Stage I have an excellent prognosis. That means the tumors are confined to the kidney and small in size, have not broken through the capsule outside the kidney. So, for Stage I, the survival rates are in excess of 90%, 95% or so; for Stage II, the survival is about 88%; stage III, the numbers drop down to in the 60, around that number; and for Stage IV, unfortunately, the survival is still not good with only 20% surviving five years. So, it really all depends on the stage of the cancer when the diagnosis is made.
Lisa Garvin: Can you catch them early, or are they caught early most of the time?
Nizar M. Tannir, MD, FACP: Yes, about 75% of renal cell carcinoma is diagnosed when the tumor is still confined to the kidney. About a quarter, 25% of these cases, unfortunately when they are diagnosed, the patient already has stage IV disease, advanced disease. And even those patients that undergo surgery with curative intent, that is nephrectomy, removal of the kidney or partial nephrectomy, removal of the tumor, that's in the kidney leaving a remnant that's healthy, unfortunately, about also 30% of those patients have recurrence post-surgery. So ultimately, we are looking at about 30% or so of patients who end up having advanced disease and need systemic therapy for their advanced disease.
Lisa Garvin: I understand too that recurrence, it can be fairly high in kidney cancers.
Nizar M. Tannir, MD, FACP: Yes, as I said, you know, about a third of the tumors or so would recur. So, the patients need to be vigilant and their physicians need to follow them, so what we call surveillance studies after their nephrectomy. Now obviously, the risk of recurrence depends on the stage where the cancer was diagnosed. You know Stage III have a higher recurrence rate than Stage II, and Stage II have a higher recurrence rate than Stage I.
Lisa Garvin: Now, what is non-clear cell renal cell carcinoma?
Nizar M. Tannir, MD, FACP: Well, as I said, renal cell cancer is not one disease. So, it is a heterogeneous disease and there are diverse subtypes. The most common is clear cell and it is about 80% of all cases. The rest, the 20% are the non-clear cell. That's a diverse group by itself. There is a type that is called papillary that can also come in two different types. There is a type I papillary and there is a type II papillary in renal cell cancer. There is another rarer form that's called chromophobe and another that's called collecting duct. There are about 5% of the cases where we really cannot pinpoint the exact type, so we refer to it as unclassified. That's when the pathologist even using the latest immunostage techniques to try to identify the tumor of origin, cannot pinpoint, cannot categorically state the type of renal cell cancer so they report this as unclassified. That's when it has features of clear cell and also clear features of say, papillary or chromophobe or collecting duct or otherwise, you know, the other subtypes. So, that's a challenge sometimes. We hope that in the future, we would have better tools available to be able to categorically identify each type by molecular diagnostic tools.
Lisa Garvin: As a medical oncologist, you would be using chemotherapy. Chemotherapy is used in what role in relation to surgery. I mean, is it usually surgery then chemo or is chemo sometimes used without surgery?
Nizar M. Tannir, MD, FACP: Well, chemotherapy plays a major role as we know in many solid tumors and in hematological malignancies. You know, when the types of solid tumors where chemotherapy is curative is germ cell tumors, but we know chemotherapy plays a major role in breast cancer treatments, colorectal cancer treatments, and others. But for renal cell, it seems like chemotherapy is not as effective as it is in these other tumor types we mentioned. So, the role of chemotherapy in renal cell cancer is limited. There is no FDA approved chemotherapy regimen or chemotherapy agent for the treatment of renal cell cancer. However, at M.D. Anderson, we have conducted several studies looking at the role of chemotherapy in renal cell cancer and I can tell you that there are patients who would benefit from chemotherapy and these are particularly those patients with clear cell renal cell carcinoma who have not responded to target therapy or immunotherapy. And even if they responded to immunotherapy or target therapy, unfortunately, the response in the majority of patients is limited and then they have progressive disease and that's when we've seen some patients respond to chemotherapy. In fact, we've reported several studies showing the benefit of chemotherapy. But in general, chemotherapy is not used upfront in patient with renal cell cancer, any type, except for the type that we call sarcomatoid renal cell carcinoma where it seems like chemotherapy does play an important role there, although unfortunately this is a very aggressive disease and incurable disease, but chemotherapy seems to be important in that area.
Lisa Garvin: Tell me about the START Trial, apparently, you are trying out some chemotherapeutic agents on renal cell carcinoma.
Nizar M. Tannir, MD, FACP:: So, again I think too, so we define the terms while chemotherapy for the patients and laymen, any drug that's given is they refer to as chemotherapy as a distinction to radiation and as a distinction to surgery. So, to differentiate from surgery and radiation, any drug is referred to as chemotherapy, but as I said, the chemotherapy term should be reserved to the cytotoxics that have been traditionally developed to target the pathways of the tumor cell themselves. Now, the START Trial, the acronym stands for Sequential Two-agent Assessment in Renal Cell Carcinoma Therapy, this is the trial that we have upfront and is up and running at M.D. Anderson with the hope that this will be also open at other centers and so, we will make it a multicenter trial. This trial is looking at recruiting patients with clear cell renal cell carcinoma who had not had pro-systemic therapy. They should have had product nephrectomy, so these are patients who have advanced disease, had their surgery already with removal of the kidney and not had any systemic therapy. And those patients get randomized, meaning randomly assigned to receive one of six sequential treatments. So, the three drugs we are using in the START Trial are FDA approved and these are Bevacizumab, Everolimus, and Pazopanib. We chose these three drugs because each has a different mechanism of action. We chose these design because until now it is not clear what is the best drug to give upfront, what is the best drug to give in the second line. And while these target therapies that are FDA approved have really changed the landscape of the treatment of renal cell carcinoma and helped a lot of patients, a lot of patients benefit from this, unfortunately, they are still not producing the ultimate goal which is curing patients. So, while patients respond and benefit, unfortunately eventually the disease does progress. So, our approach has been and this is now, you know in the clinic, is to treat the patient with one agent upfront and then at the time of progression to proceed and give them a second line therapy. But as I said, patients, we do not know which patients respond to what drug and this trial is looking at answering many questions, what would be the best sequence among the several sequences available and when you are using three drugs and the protocol is treating patients and the same protocol sequentially twice in the first line and then in the second line, you get six sequences. So, this trial will answer which sequence is best and also, as importantly, we are looking at several biomarker studies, both tissue based, blood borne and also functional imaging to try to see which patients respond best to which therapies. So, this would be the ultimate personalized medicine where we are trying to identify those patients who would respond better to, say, Bevacizumab versus Pazopanib versus Everolimus. So, patients will have blood drawn, blood test at baseline, and then at different time points during the trial, and will have also a baseline functional imaging study that consists of a CAT scan perfusion, Perfusion CAT scan at baseline and then at different time points after treatment started. And so, we will be looking at the CAT scan, the Perfusion CAT scans and the blood that we will look at, test circulating biomarkers in the blood of patients receiving these target agents with the idea of correlating what we find in the blood and what we see on these Perfusion CAT scans, correlate that with their response to therapy. And the hope is to identify a signature or a change in the perfusion CAT scans that will tell us this agent works best for this type of patient. And through mathematical modeling, we will be looking at identifying, assessing the change in blood flow, permeability, blood volume, et cetera with the Perfusion CAT scans.
Lisa Garvin:: Thank you very much for being with us today. 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 next week for the next podcast in our series.