Ravi Munver, MD, FACS, Vice Chair of Urology and Chief of Minimally Invasive and Robotic Urologic Surgery at Hackensack University Medical Center talks about a new treatment that can save patients with urothelial cancer.
I wanted to ask you about kidney cancer. For our viewers who, you know, may not be – may have heard of it but may not be super familiar, what’s going on?
MUNVER: There are two main types of kidney cancers that we see commonly in the United States. The first is the type of cancer that grows from the outside of the kidney or the meat of the kidney, and the second type of kidney cancer grows from the inside of the kidney where the urine is formed. The first type of cancer is called renal cell carcinoma. While the second type of cancer traditionally was called transitional cell cancer, but has name changed over the last several years. The second type of cancer is called urothelial cancer. This is the same type of cancer that grows in the bladder, and bladder cancer is very common among individuals as they get older.
You said this is the kind that starts from the inside. Can you describe where it usually starts in the kidney?
MUNVER: Sure. So, the lining of the inside of the bladder also lines the inside of the kidney tubes called the ureters and also travels up to the kidney and lines the inside of the kidney. So, where the urine is made and collects in the kidney before it passes down the kidney tube or the ureter into the bladder, all of that lining is the same type of cell. They are called urothelial cells. Cancer can arise anywhere along the urinary tract from the inside of the kidney, the inside of the ureters, or the inside of the bladder.
What are the symptoms and is it possible to have this cancer without knowing it, without having very many symptoms?
MUNVER: Certainly. Most people who develop this type of cancer do not have any symptoms initially, but initially they may be detected by going to a physician’s office and having a urine check. The urine may show some blood in their urine, and when there is blood in the urine, a full workup is required because that blood can arise from anywhere from the kidney all the way down to the bladder. Two types of things are done. One is an imaging study, usually a cat scan or an MRI, and the second is a look inside the bladder. The look inside the bladder is to look for bladder cancer, but the imaging study is to look for cancer above the level of the bladder, so within the kidney itself or in the kidney tube.
If cancer is detected inside the kidney, how is it commonly treated?
MUNVER: There are two ways to treat kidney cancers that grow from inside the kidney. One is going up the ureter with a small telescope and treating the tumor if it’s small with either a laser or biopsying it or cauterizing it, but it’s only available for select tumors that are small and in easy to target locations. The majority of patients who have this type of tumor that grows or cancer that grows inside the kidney need their entire kidney and their kidney tube, called the ureter, removed.
When you lose that kidney, what kind of complications are you looking at? Certainly, we have two. So, if you lose one are you still OK? Are you still functioning all right? Or do you need transplantation?
MUNVER: The younger someone is and the better their kidney function is in terms of whether they have medical diseases that can affect kidney function, traditionally, removing one kidney should allow you to function with a second kidney. However, this type of cancer we typically see in individuals older than 50, 60 or 70 years of age. Many individuals have other diseases that can affect their kidney function. So, removing one kidney can be very detrimental to their health, because only having one kidney, if that kidney doesn’t function well, may need to have dialysis or other adverse consequences from only having one kidney that can’t really clear all of the waste products from the bloodstream.
Can you talk to me a little bit about how the mitogel gel works inside the body and how it’s affective as a treatment?
MUNVER: For patients who need a type of treatment that can spare their kidney without removal, these patients will typically have to have multiple endoscopic surgeries by putting a telescope through the bladder up into the kidney and treating the tumors. If the tumors were not fully treated and if they returned, they would just need procedure after procedure and eventually would go to a nephroureterectomy — removal of the kidney and the ureter. Previously, there was no good treatment for us, in terms of any medicine that could treat the types of tumors in the kidney. Now for bladder cancer, we use a chemotherapeutic agent called mitomycin. It is a liquid that we instill into the bladder once a week for six weeks. The patients would keep that liquid in their bladder, and they would urinate it out about a couple of hours later, and that would bathe the inner lining of the bladder. That would work effectively. In the kidney, it does not work that effectively because while we can instill that liquid up into the kidney with a small catheter, the minute that urine passed, it would also make the mitomycin liquid pass down the ureter into the bladder. So, it would not have a long dwell time in the kidney and would not be able to stay in contact with the lining and the cells of the kidney to prevent the recurrence of these tumors. That had been the challenge for decades. Recently in 2020 mitomycin gel was FDA approved for use. Now, this is the same mitomycin liquid mixed with a hydrogel. Think of it as a gelatinous type of this chemotherapeutic agent that we can inject into the kidney, and because it’s a gel form, it stays in the kidney for a few hours. It would then liquefy, mix with the urine and would then pass down the ureter into the bladder. This is why this is such a novel agent allowing us to treat specific individuals that have this type of cancer, typically the type of cancer where you want to be able to save the kidney.
That was my question. You mentioned it’s like a gelatin or a Jell-O. Because it’s staying in the area longer before it passes with the urine, that’s enough time for it to effectively work on those areas?
MUNVER: Correct. We needed the dwell time to be at least one to two hours. These tests have shown that the gel stays in its form for at least one or two hours and closer to four to six hours. That’s why this is such a novel agent.
Again, it doesn’t have to be removed because it will just pass naturally through the system?
MUNVER: That is correct. It will pass naturally through the system within several of hours.
Can you talk to me a little bit about Ralph and his case?
MUNVER: Sure. Ralph was sent to me by one of my partners who diagnosed him with a decent sized tumor in his kidney. The tumor was about two centimeters in size, about the size of a quarter. On biopsy it showed that it was a low grade. Just for clarification, the treatment we are discussing is for low grade urothelial cancer of the kidney. A high grade or a more aggressive form of this cancer should be treated with a nephroureterectomy. The majority of these tumors that we oftentimes find are of low grade. We were still treating them the same way we treated the more aggressive form with nephroureterectomy because we had no way of preventing their recurrence. So, after his biopsy, he was referred to me for an endoscopic treatment. I explored the inside of the kidney with a ureteroscope, which is a small telescope, and treated about 60 to 70 percent of the tumor. Due to its size, I couldn’t treat it all of it in one shot as the laser fiber is very small as is the telescope. It takes an extensive amount of time to treat such a size tumor as what Ralph had. I brought him back a few weeks later and went back up and treated the rest of the tumor. Then I brought him back about six to eight weeks later to have a look to see if all of the tumor was gone, and guess what? It had come back. It wasn’t as big as the initial tumor, but it did come back. I was able to treat it easily with the laser in about 15-20 minutes and he was sent home in a same day surgery. I then brought him back about three months later and looked up again, and guess what? The tumor was back. At that point, I gave him some options. I said that we can remove your kidney even though this is a low-grade tumor. These are the types of tumors that don’t typically metastasize, but it is problematic that we keep bringing you back so often and we will likely have to keep doing this because we don’t have any other options. In the meantime, we were working with our institution, Hackensack University Medical Center, with our pharmacy team, our administration, as well as the company that developed this product to see if we could bring this product into our institution. As you can imaging, it is an expensive product. It wasn’t covered by a lot of insurances initially, and because of that, it wasn’t feasible to spend thousands of dollars for this chemotherapeutic agent without receiving reimbursement. Well, lo and behold, by 2021, things changed. CPT codes changed. Insurances started to cover this treatment. During this time, we were able to get Ralph approved for this treatment. Now I initially treated him surgically last year in 2020 and his treatments had been going on for about a year. Finally, we were able to treat him with the mitomycin gel. I first looked up his ureter and into his kidney and verified that there were no tumors since I had just treated him. We waited about four to six weeks, and then we started the treatments. The treatments involve once a week for six weeks installation of the mitomycin gel into the kidney. It is a pretty straightforward procedure. Using a telescope inserted into the bladder, we put a thin catheter up the ureter into the part where the urine is made in the kidney. We inject the mitomycin gel, remove the catheter, remove the telescope, and we send him home. He would come back one week later and does that once a week for six weeks. At the six-week mark, he’s done with his treatments. What happens next? We wait about six to eight weeks, and we will go back and have a look up in the kidney. We expect to see good results. Now, Ralph was our first patient, and we are among the early adopting institutions in the country to be administering this therapy. We were the first major hospital system in New Jersey and the first in Bergen County to be using this therapy. During the course of his treatments, I was curious to see what things looked like at three weeks. So at the three week mark, I actually looked up Ralph’s ureter and into the kidney and noted no evidence of tumor. So, that was a really good sign. It meant that tumors were not recurring during the course of this treatment. Then we completed the next three courses over the next three weeks and we will see how things look in the next couple of months.
What kind of a difference could this make for patients like Ralph? Would he be losing his kidney if he had no other treatment option down the road?
MUNVER: For Ralph, because his tumor kept recurring, he had to undergo surgical procedures under anesthesia every few months since tumor kept recurring. Without this treatment to help prevent tumor recurrence, I would eventually have recommended him to have a nephroureterectomy to remove the kidney and the ureter.
How is he doing now? I mean, he’s full of energy.
MUNVER: He’s doing great. He has been great through the entire process, even while I was going up and treating his tumor time after time. He was very optimistic, very thankful. Patients like Ralph with such a great outlook, helps with their recovery. I think it really helped his tumor disease as well. Patients who are healthy, patients who are taking care of themselves and mentally in a good state of mind, tend to do better.
Is there any evidence of cancer? You had mentioned was it three weeks ago that you took a look?
MUNVER: After this three-week treatment, I had a look, and there was no evidence of cancer.
When was the last time that you took a look?
MUNVER: We finished his treatment approximately four weeks ago, and what the studies for this mitomycin gel have shown is that there is a 59 percent effectiveness, or complete response, with this treatment. This data is based on the clinical trials that were performed, and the durability of this treatment at 12 months was 84 percent. So, eighty-four percent of patients did not have a recurrence of their tumors based on the large, multi-institutional clinical trial that led to the FDA approval in 2020.
Is there anything I didn’t ask you, doctor, that you would want people to know about this option?
MUNVER: I think the important thing to know is that this tumor we diagnose in about five to seven thousand patients a year in this country. You may think, well, that’s not a lot of patients. However, this type of tumor can arise in any patient who has bladder cancer. The bladder cancer incidence in this country is extremely high. We are talking between seventy thousand and one hundred thousand patients a year. So, anyone with bladder cancer has a small percentage of developing this type of tumor because it’s the same lining and the same type of cell. For patients with bladder cancer, they are all getting surveilled for their upper urinary tract, which means that they are all getting some kind of an imaging study to make sure that tumors don’t arise in the kidney tubes or in the kidney themselves. When a tumor does arise, now not only can we treat it endoscopically, but we can also prevent the recurrence with this mitomycin gel chemotherapeutic agent. You know, for someone like myself, I am a kidney saving surgeon, and what that means is I do a lot of kidney cancer surgery. I perform robotic surgery for partial nephrectomies to cut out tumors that grow on the outside of kidneys to prevent patients from losing their entire kidneys. I also do my best to save patients who have these types of tumors that grow from the inside of their kidneys called urothelial cell carcinoma. As a result, I do a lot of these endoscopic surgeries. Now I have an agent that I can use to prevent the recurrences after I have treated the tumor endoscopically. I am also the chief of living donor kidney surgery at our institution. So, for patients that need kidney transplants, I am the surgeon who takes the kidney out from someone who’s donating to them. I know what it is like for patients to be on dialysis. I know what it is like for patients who have compromised kidney function. As a kidney saving surgeon, this type of treatment really adds to our armamentarium, our supply of different options that we can give our patients.
How long could Ralph have had the cancer and had to develop? Is this a slow growing cancer? Because he had mentioned for years there had been some, you know, urinary tract problems, difficulty urinating, blood in his urine for a long time, but just it never got to that level. Does it really grow that slowly?
MUNVER: Absolutely. These tumors do grow slowly initially, but they can metastasize at any point. So, when we treat these types of tumors, whether they are in the kidney or in the bladder, after we treat them and remove them, we will do a surveillance look inside the bladder or inside the kidney at three months after that initial treatment. Why three months, because they don’t grow that quickly. If we were to have had a look in Ralph’s kidney at a month or two months, we may not see anything unusual. So, we wait three months. If a patient is clear of tumor recurrence, we will check in another three months after that. We will continue to do three months surveillance examinations inside the patient’s kidney over the course of that first year. If they are clear at a year, we can consider extending that interval to six months in the second year, and then annually after two years.
Interview conducted by Ivanhoe Broadcast News in December 2018.
END OF INTERVIEW
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