Transcription:
Breaking Down Kidney Cancer

Dr. John Leonard: (Host) Welcome to Weill Cornell Medicine CancerCast, conversations about new developments in medicine, cancer care and research. I'm your host, Dr. John Leonard. And today on the podcast, we'll be talking about all things related to kidney cancer. Our guest for this episode is Dr. Ana Molina, a Medical Oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital.

Dr. Molina specializes in the care of patients with genitourinary, or GU, cancers. And this area encompasses cancers of the kidney, the bladder, and the prostate, to name a few. Dr. Molina's work focuses primarily on caring for patients with these cancers and she has a special interest and expertise in kidney cancer, which is our topic for today.

I'm looking forward to asking her more about this form of cancer, from signs and symptoms to the latest updates in treatment and care. So, Dr. Molina, thank you for joining us today. It's great to have you here. We have clinic some of the same days, but usually we're running in our own circles with our own patients. So it's good to talk with you today and learn about your work and your interests. So thank you.

Dr. Ana Molina: (Guest) Hi, John. It's a pleasure to be here today.

Dr. John Leonard: So I'd like to start by asking you what got you excited about working in oncology generally, and particularly in the area of genitourinary cancer, which like many areas of oncology seems to get more and more specialized with time as the treatments become more precise and in some ways complex. How'd you end up in this area?

Dr. Ana Molina: Excellent question. So, in terms of practicing medicine, I've always wanted to practice medicine for as long as I can remember. I've been drawn specifically to oncology since medical school and the patients I interacted with during my training in medical school. And then, more importantly, during my training in oncology at Memorial Sloan Kettering, I met Robert Motzer, who's a world-renowned kidney cancer expert. And as I rotated through his clinics, I was able to meet a lot of patients with kidney cancer. And at the time, it was just the beginning of when we finally had medications that could arrest or stop the growth of these cancers. It was when the targeted therapies were starting to get approved and just understanding the biology of kidney cancer. How we chose treatment options to target the abnormalities in kidney cancer was very exciting to me. I've also enjoyed the interactions with the patients and families. I do see this as a chronic disease, although it can be a very tough journey for many patients, especially the patients with advanced cancer, I feel that I've been able to make a significant impact not only in controlling their disease, but also helping the whole family through this journey.

Dr. John Leonard: That's a great entrance to our topic today. Why don't we start by just a little bit of background on kidney cancer.

People think of breast cancer, prostate cancer, colon cancer, being very common cancers. Where does kidney cancer fit from the perspective of frequency of cancers and how often it pops up? And perhaps we can get into the different types a little bit as we start to get into that area.

Dr. Ana Molina: So kidney cancer is one of the 10 most common cancers in both men and women. So although it's not as common as breast and prostate cancer, we do see about 79,000 new cases a year in the United States. And the majority of these cases are predominantly in males. So there is a male predominance in this type of cancer.

When we talk about kidney cancers in general, you're usually discussing kidney cortex cancers, and what we call renal pelvis cancers. They are two different types of cancers. When I talk about kidney cancer, I think of renal cell carcinoma. This is a type of cell in the kidney. And then we also have a separate type of cancer called urothelial, which is a very different kidney cancer, that occurs in the renal pelvis. And the talk today, we're primarily going to focus on kidney cancer as renal cell carcinoma.

Dr. John Leonard: You mentioned the male predominance. What is behind that? Or do we know, is it lifestyle? Is it genetics? What are some of the other risk factors that we think about in patients that are diagnosed with kidney cancer?

Dr. Ana Molina: So we don't know why males tend to get this cancer more often. We can talk a little bit about the common risk factors and maybe it is lifestyle changes. So for example, we know that smoking increases the risk of developing kidney cancer, similarly to other cancers. Having high blood pressure is a risk for kidney cancer development. Also obesity, so patients who are very overweight have a higher risk of developing kidney cancer. There are also things such as family history. So, patients who have a strong family history of kidney cancer, meaning that there are inherited kidney cancers, have a higher chance of developing this type of cancer.

There are also things such as workplace exposures. So, I have met a couple of patients who were exposed to the 9/11 disaster and developed these types of cancers. We also see patients with advanced kidney disease and what I mean by that are patients who are on dialysis. And these patients are at higher risk of developing kidney cancer as well.

Dr. John Leonard: How are most patients diagnosed with kidney cancer? People are familiar with checking your PSA or getting your mammogram. Is there any kind of screening test that's recommended? And how does it show up for most patients? And I'm sure that's different if it's localized versus advanced stage disease.

Dr. Ana Molina: So, interestingly, this cancer in the majority of patients is found incidentally, meaning by accident. A patient comes in with a gallbladder issue. They get a CAT scan and we find a renal mass, a kidney mass. Or they're presenting for heart surgery or something and we find nodules in the lungs that then leads to a diagnosis.

Common signs and symptoms of kidney cancer include blood in the urine, which is called hematuria, oftentimes painless. Patients can feel fatigue, loss of appetite, weight loss, some patients present with low red blood cell counts called anemia. So your doctor obtains your routine blood work and notices that you have anemia.

And then some patients will describe flank pain or pain in the lower back. Some patients may even palpate or feel a lump in their lower back. But again, most patients are presenting incidentally by accident. We detect this cancer by scan. So someone's coming in, as I said, for another issue, we get a CAT scan and we find a kidney mass or find disease in other parts of the body.

The reason it's detected incidentally is oftentimes you don't have symptoms. The kidneys live in the back, an area called the retroperitoneum, and these tumors can grow to very large sizes and not cause symptoms because they're on the outer part of the kidney. It's not until they start spreading more towards the middle part of the kidney that you start having things such as blood in the urine and discomfort. So, oftentimes patients do not have symptoms with this cancer.

Dr. John Leonard: So, I'll ask you two questions about the diagnosis or this incidental finding, which is an interesting scenario. And I think people think about well, if it's only found by a scan, should I go out and get a scan and get screened for this? And that comes up a lot in people worried about pancreatic cancer, or other things. Is there any thought or evidence around doing periodic screening for kidney cancer through some sort of imaging? Or is that not something that's going to be efficient to find early.

Dr. Ana Molina: That's a great question. So, although some tests can find kidney cancers early, such as routine urinalysis, you find blood in the urine, it leads you to do an extensive workup or you get an ultrasound for another reason; none of these are recommended for screening for kidney cancer in the average patient with the average risk for developing kidney cancer.

However, if you are a patient that has a family history, other members with kidney cancers, then that's different. In those scenarios, patients will typically get ultrasounds, but you are typically testing the patients to see if they inherited any genes that predispose them to developing kidney cancers. And then once that is identified, you can proceed with surveillance. So, for example, if I have a patient that has a familial type of kidney cancer, we've identified that it's inherited by checking the blood for inherited genes, in those patients, we then test the family members, refer them to genetic counseling, and then we have a slew of screening studies that we would perform.

Dr. John Leonard: So somebody who has a parent or a sibling with kidney cancer, it sounds like that person, not the person with the cancer, but the relative, should get a genetic screening. Is that a general statement or are there certain categories of people? Is it just one relative and how do they do that? What are they looking for, generally speaking?

Dr. Ana Molina: So for genetic testing, we certainly test any patient with kidney cancer under the age of 45. This is a cancer of the aging, meaning that we typically find these tumors in patients who are in their mid-sixties and above. So, anyone with a kidney tumor that's diagnosed under the age of 45; we certainly do genetic testing in those patients and offer the testing to the family members. In the majority of patients with kidney cancer, who developed these tumors in their sixties and so forth; we're not doing genetic testing or counseling, unless there's a strong family history of multiple cancers, or the patients themselves have multiple different types of cancers. Then in those patients, we would do the genetic testing. And then if it's positive, offer the testing to the family members.

Dr. John Leonard: Got it. Now, that makes sense. I wanted to come back to the incidental finding issue again. And as you know, I'm a lymphoma specialist. You mentioned the gallbladder example where patients come in with a gallbladder issue and get a scan and it shows something in the kidney. Certainly plenty of my patients with lymphoma, occasionally we'll see something in the kidney or elsewhere, and this whole concept of incidental findings. Maybe you could just take a second and mention, because I'm sure this comes up a lot in your practice in someone who's not yet diagnosed, what are the other things that are found in the kidneys incidentally? I know people can get cysts and other things, but generally speaking, what are the other things that one can find incidentally or otherwise in the kidney? And then how do you approach it to say, well, this is a kidney cancer versus something that tends to be more benign?

Dr. Ana Molina: So, the most common finding when we see a mass or a nodule in the kidney, the most common diagnosis is renal cell carcinoma or kidney cancer, but there are other things that can grow in the kidneys. We can have benign tumors, there are tumors called oncocytomas, that radiographically or on scans looks similar to clear cell kidney cancer, but these are benign.

There are tumors called angiomyolipoma look different from a clear cell kidney cancer. You can have, as you mentioned, cysts, very simple cysts, very complex cysts, so different variations of cysts. You can have other tumors that grow in the kidney. As I mentioned before, the urothelial or similar to bladder cancers grow in the kidney. These tend to be more central. If you think of the kidney as a kidney bean, the outer part being where renal cell grows and the middle part were urothelial tumors grow. You can have other tumors aside from these kidney tumors, such as sarcomas. We have seen lymphomas, not very commonly, but we have seen lymphomas in the kidney as well as spread from other cancers.

Dr. John Leonard: So when you see an abnormality in the kidney it probably depends a little bit on the test, right? If a patient had a CT scan versus an ultrasound, what's the typical pattern of how that's pursued? I guess in some cases the radiologists will say, well, we think it's this, keep an eye on it versus go get a biopsy. And how is that generally approached in most cases?

Dr. Ana Molina: So, there are a couple of things that we look at. One is the size of the nodule or tumor. So very small nodules, one centimeter or two centimeter, even three centimeters. We can oftentimes watch carefully. By watch, I mean, we can follow those and usually the surgeons are following these patients with scans every six months or so. So when we identify a kidney mass, nodule, or tumor, all of which mean the same, we look at the size of the nodule. So with very small nodules, usually less than three centimeters; based on what they look like radiographically. So oftentimes the radiologist will say, this looks like a renal cell carcinoma, or this looks like a cyst, or this looks like something benign.

We typically can follow those with what we call surveillance scans. So the urologist usually follows these patients with either a CT scan or an MRI every six months or so to see if there's any change in these nodules. If, however, patients present with large masses and large, I mean, anything above seven centimeters, 10 centimeters and more, and this looks like a clear cell kidney cancer radiographically; we are either going to do one of two things. We may biopsy that nodule, if there's no evidence of any cancer anywhere else in the body, or that patient may go straight to surgery. And depending on the size of the mass or nodule, patients will undergo one of two surgeries. Either what's called a partial nephrectomy where they have just part of the kidney removed where the cancer or tumor is located, or they will undergo a radical nephrectomy where the entire kidney is removed if we're dealing with a very large kidney mass.

Dr. John Leonard: Well, let's get into what one might find after surgery. So in a localized kidney mass, let's say, the patient's had surgery and it's removed. What are the certain aspects of the pathology report that you are focused on as you try to think about what this patient's longer-term risk is and how to address it?

Dr. Ana Molina: So, once the patient has the mass removed, the pathologist looks at it under the microscope and they can tell us what subtype of cancer this patient has. First, they confirm whether we're dealing with cancer. And secondly, they can tell us if this is a common type of kidney cancer, that's the clear cell or are we dealing with some of the rare kidney cancers, which all fall within a category called the non-clear cells.

Once we know what the subtype is, the next step is to know what the stage is, and stage means location. So, is this a tumor that's just limited to the kidney? Is this a large tumor, but limited to the kidney? Or are we dealing with a tumor that has spread beyond the kidney, into the blood vessels that come into the kidney, outside of the kidney, or are we dealing with a more extensive tumor where we're now seeing spread to a little gland that sits on top of the kidney called the adrenal gland or surrounding lymph nodes.

So depending on the stage, you will treat the patient differently. So for example, for early stage tumors, such as a small tumor that is less than seven centimeters, limited to the kidney, we're going to proceed with surveillance, meaning we're monitoring those patients on different intervals, looking to make sure that there's no return of the cancer. In early stage kidney cancer is very rare to have return of the cancer. As opposed to more advanced stage, like stage three, meaning a tumor that is invading or involving some of the major veins of the kidney or the adrenal gland; those patients have a high risk of this cancer returning, typically within the first two years. But it can return at any time.

So in these patients, we are talking about what we call adjuvant therapy or treatment after surgery to try to reduce the risk of recurrence. And just this year we had the approval of an immunotherapy called Keytruda or pembrolizumab that we can now give patients with high-risk kidney cancer who have had surgery. We give patients this medication for a year's time. And this has been shown to reduce the risk of recurrence. In patients with more advanced cancer, stage four, some of these patients do have surgery. We are treating them with medications after they have had the kidney removed. And we are following these patients with scans typically every three months.

Dr. John Leonard: So, I want to come back to the different systemic therapies and you mentioned the immunotherapy a second ago, but very briefly, are there other cancers that spread to the kidney? I know lymphoma does, but beyond that, are there other scenarios where that is also a possibility. In those cases, you probably know that the patient has the other cancer, but as you mentioned, it wouldn’t be rare for someone to have an incidental finding in the kidney when they have a cancer elsewhere. Are there other cancers that tend to affect the kidney?

Dr. Ana Molina: So the other major cancer that tends to affect the kidney is a cancer called urothelial carcinoma. And this is a cancer of the urinary tract, meaning from the kidney down to the ureters, down to the bladder. And this cancer can occur anywhere along that lining and urothelial carcinoma is another cancer that can arise from the kidneys specifically the renal pelvis or the kidney pelvis, which is that middle aspect of the kidney. It's important to make that diagnosis because those cancers are treated very differently. In general, we're not using the same medications that we use for renal cell carcinoma. We are typically using chemotherapy, instead of the drugs that we use for kidney cancer, which are targeted therapies and immunotherapy.

Dr. John Leonard: So let's focus a little bit more on the patients that have a kidney cancer that is more advanced stage. So, you mentioned that the adjuvant treatment with the immunotherapy, the immune checkpoint inhibitor for a year, what is the typical strategy for patients that have more advanced stage disease?

And I guess let's start with, where does kidney cancer tend to spread beyond the local area? What other organs can it go to? And then what are the general principles of how you standardly approach patients that have disease that has either come back elsewhere or is elsewhere when it's diagnosed.

Dr. Ana Molina: So, kidney cancer can spread to multiple areas. Some of the common sites where we find this cancer include the lungs. We can see kidney cancer spreading to the bones. Organs surrounding the kidney, such as the adrenal glands, the pancreas, lymph nodes, other sites such as the liver and brain. So, we are looking for cancer at different sites when a patient presents with kidney cancer, by doing different scans, we are getting CAT scans of the chest, abdomen, pelvis. We do obtain a baseline brain MRI to assess the brain as well before we start therapy. And then in terms of the different treatments that we have for kidney cancer, I think one unique aspect of treating this cancer is that we don't use standard chemotherapy.

These standard chemotherapies have been tried in the past, they were not very effective in treating these cancers. So, for a long time, we had very little, if any effective treatments for advanced kidney cancer and in the past almost 20 years, 17 years or so, numerous therapies have been approved. And the reason we have all of these numerous therapies is we understand the biology of this cancer. We know that these cancers have special proteins or the cancer cells use proteins to grow and survive. And we are able to use what are called targeted therapies or drugs that can block these proteins and cause the cancer cells to die. We also, in the past few years have introduced immunotherapy drugs and these work very differently than the targeted drugs.

In general, these drugs can boost the immune response against kidney cancer cells. So, we went from really having minimal therapies to treat patients with advanced kidney cancer to now having numerous agents, not only the targeted therapies, immunotherapy agents as well. And the newest thing in the past few years have been, that we now combine the targeted therapies and the immunotherapies to treat patients with advanced kidney cancer.

Dr. John Leonard: So these are typically pills that patients are taking or infusions? What are some of the drugs that are commonly used beyond the immune checkpoint inhibitors that you mentioned?

Dr. Ana Molina: The targeted drugs are pills. There are different pills that are approved for the use in patients with kidney cancer. So, some of the older drugs were sunitinib or pazopanib, and these are all called tyrosine kinase inhibitors. Some of the newer drugs or frequently used drugs in combinations include axitinib, lenvatinib, cabozantinib.

And these are all drugs that are given at different schedules. Some are given daily, some are given twice a day. Some are given four weeks on, two weeks off. They are very different from chemotherapy in that their side effects are different, so they can cause things such as elevations in blood pressures so we're commonly checking blood pressures in these patients.

We can see rashes develop. We can see mouth sores, different abnormalities in lab tests. So, we're frequently checking lab tests when our patients come in and see us. The immunotherapy are different. So these are administered through the vein on different schedules as well. Some of the drugs such as nivolumab is administered every two weeks or every four weeks. There's another immunotherapy drug called pembrolizumab. That one's administered either every three weeks or six weeks. And the toxicity or side effects of the immunotherapy drugs are very different from the targeted drugs.

Some of the things that we see with immunotherapy include rashes. We can get some shortness of breath. We can get some diarrhea and rarely, but very importantly, we're always monitoring for immune-related toxicity meaning the different organs can become very inflamed from the immune system, such as the liver. We can see lab values from the liver go very high. Patients can develop inflammation in the lungs from the immune response to these therapies.

And at times we do have to stop the immunotherapy. And in some cases we do have to give drugs such as prednisone or anti-inflammatories to try to calm down the immune response.

Dr. John Leonard: In general, how have they made a big impact for patients? Is it living longer? Is it controlling symptoms? Is it controlling the disease? Is it all of the above? You mentioned that chemotherapy didn't work very well in this particular type, but it sounds like these have made a much more significant impact.

Dr. Ana Molina: Absolutely. So, we talk about the evolution of kidney cancer therapy. Before the targeted therapies were available, median survival for patients was about a year, a year and a half. And we have gone to a much longer survival. Some patients are surviving for over five, 10 years on these different agents. So, we've definitely made a dramatic difference in not only the way we can control the cancer, but we're seeing more and more patients living with stable disease. And as I mentioned earlier, we do see this as a chronic disease. And we are able to control the disease and improve patient's quality of life for extended periods of time.

Dr. John Leonard: Before we wrap up, I wanted to ask you about research. I know that that's a big aspect of your work and integrating it into patient care. What are some new directions that you and your team are pursuing or that you're excited about that are things that patients interested in kidney cancer should keep an eye on and learn more about?

Dr. Ana Molina: I think some of the exciting things in kidney cancer, one is there are a lot of trials that are available. So, if you are diagnosed or know someone that is diagnosed with advanced kidney cancer or even earlier stages of kidney cancer, but at high risk for developing spread of the cancer, look or search for clinical trial possibilities. There are beyond the combinations that we're currently using, such as targeted drugs and immunotherapy drugs, we are looking at other novel agents. So, for example, there's a drug called belzutifan, which is another targeted drug but this drug targets HIF alpha or hypoxia inducible factor. This is another protein by which these cancer cells can grow and survive. So we are now looking at using that agent in combination with some of our current targeted therapies and our current immunotherapy drugs.

Very interestingly this year, belzutifan was approved for patients who have the familial kidney cancer syndrome called Von Hippel-Lindau syndrome. So, this is the first drug approved for this group of patients who have the possibility of developing kidney cancers. And they also develop other types of cancers throughout the body. And we can now offer them this new drug belzutifan to stop the growth of these cancers and improve overall quality of life.

At Weill Cornell, we're looking at other ways to develop new drugs that inhibit kidney cancer growth. So, Professor Lorraine Gudas, who's the chairperson of pharmacology and toxicology at our center, a lot of exciting work that is ongoing in her lab. We have developed a kidney cancer mouse model that we are working with trying to mimic kidney cancer development and with the goal to then try to target those tumors with various drugs, as we study the tumors further in an effort to try to come up with newer drugs to inhibit the kidney cancer growth beyond the immunotherapy and targeted drugs that we currently have.

It's important to note that although we've come a long way and we have great treatment options for patients, not all patients can receive these agents. And in general, the treatment of advanced kidney cancer does not result in cure. Very few cases do we see complete resolution or disappearance of cancer.

Dr. John Leonard: It sounds like one of the aspects of care of patients that is very important based on what you've said is having access to a multidisciplinary team where you're dealing with experts in medical oncology, in urology, in imaging, it sounds like that's an essential part of care and potentially something that can make a big impact for patients having access to all of those specialists in kidney cancer in one place. Is that a fair statement?

Dr. Ana Molina: Absolutely. Having a multi-disciplinary team is very important because you can address different issues as they arise. So for example, if I'm treating a patient that has a kidney cancer and they develop one site of disease, let's say for example, a bony lesion, but the rest of the cancer is very well controlled, I present the case in what we call our tumor board, which is a group of physicians in genitourinary cancer. So this consists of our radiation oncologists, our radiologists, other medical oncologists, surgeons, pathologists, the entire group gets together. We review the case and talk about how can we target that one lesion, whether it's ablation, radiotherapy, try to come up with a unique or individualized plan for each patient.

Dr. John Leonard: Well, thank you very much for joining us today, Dr. Molina. This has been a very illuminating discussion about an important area of oncology, and I know our audience certainly benefited from hearing your perspectives and what's new in this field. So thanks for joining us.

Dr. Ana Molina: Thank you for having me. It's been a pleasure.

Dr. John Leonard: I'd like to invite our audience to download, subscribe, rate, and review CancerCast on Apple podcast, Google podcasts, Spotify, or online at Weill Cornell.org. We also encourage you to write to us at cancercast@med.cornell.edu, with questions, comments, and topics you'd like to see us cover more in depth in the future.

That's it for CancerCast, conversations about new developments in medicine, cancer care and research. I'm Dr. John Leonard. Thanks for tuning in.

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