Transcription:
Improving the Diagnosis and Management of Renal Masses and Localized Renal Cancer

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me is Dr. Hiten Patel. He's an Assistant Professor of Urology at Northwestern Medicine. He's here to discuss improving diagnosis and management of localized kidney cancer. Dr. Patel, it's a pleasure to have you join us today. And we're going to talk about diagnosing and treating localized kidney cancer. But before we do, I'd like you to tell us a little bit about yourself. You're new to Northwestern Medicine. Give us a little bit of a background, your expertise and how you came to Northwestern.

Dr Hiten Patel: Hey, thank you very much, Melanie. My name is Hiten Patel, and I am a urologist specializing in generally diagnosis and treatment of urologic cancers and my clinical practice and research focus on prostate and kidney cancer. I completed my medical degree at Johns Hopkins, as well as a master's in Public Health. And I stayed on to train there in urologic surgery for residency. And I've been in the Chicago area now for about two years, and have had some specialized training through the Society of Urologic Oncology at Loyola University Medical Center. And I'm very happy and excited to be joining the faculty at Northwestern. And I know the department provides both excellent patient care and opportunities for research and innovation. So my goal is to really help improve the lives of patients, either at risk for or diagnosed with a urologic cancer.

Melanie Cole (Host): Well, thank you for sharing that. And we'll get you on to do plenty of these podcasts, because what a great way to hear about your expertise. So for today's, let's focus a little bit on your research and clinical expertise with kidney cancer. Tell us a little bit about some risk factors and how patients present.

Dr Hiten Patel: Yeah. So there are several known risk factors for kidney cancer and some of them are similar to other malignancies like smoking, sometimes higher body mass index, things specific to kidney cancer include hypertension, which is something that the kidneys contribute to and underlying genetics, which can all be risk factors for developing kidney cancer. And what we know is that the incidence of kidney cancer over the last few decades really went up quite a bit and then flatlined around 2010. So a question was, "Well, why did this incidence go up? Was it because of our habits?" But it turns out it was due to a lot of incidental diagnoses from greater use of cross-sectional imaging, CTs and MRIs. And basically, we found tumors in the kidney by accident. People were having CTs for other reasons like, "Oh, I have an abdominal ache here," and couldn't figure out what was going on, and they just end up finding this kidney tumor, even though it's not related to their pain.

And this changed the typical patient we saw, which became basically asymptomatic now. And the classic symptoms or signs we used to see were blood in the urine, flank pain, or a palpable mass, but that became much less common. And about 50% of patients now have what we call a localized small renal mass. And this is a tumor that's 4 centimeters or less in size, no evidence of any kind of distant spread. And in one of our studies, you know, we pulled data from surgical series and found about 20% of these tumors are actually benign, so they're not really a kidney cancer, these renal masses; 60% were probably low-grade cancers and 20% are what we consider higher grade cancers.

Melanie Cole (Host): Well, then what's the treatment options for patients once you've determined that it is localized kidney tumors, what are we doing for them?

Dr Hiten Patel: So patients diagnosed with a localized tumor like this, especially the small renal masses, have several options. We performed a systematic review funded by the Agency for Healthcare Research and Quality. And what we did was evaluate how we diagnose and manage localized kidney cancer. And these were findings that the American Urologic Association used to create their clinical guidelines. And so treatment options in general include a radical nephrectomy, which is removing the entire kidney, which contains a tumor or what we consider nephron-sparing approaches. And these nephron-sparing approaches included partial nephrectomy, where we surgically cut out the tumor while sparing most of the kidney and thermal ablation, which can either freeze or heat the tumor without removing it. Active surveillance is the last or the fourth option, and is a nephron-sparing option, the maximal nepron-sparing, where we actually watch the tumor with imaging over time and only do delayed intervention if the tumor grows or meets other trigger criteria.

And we have experience with active surveillance for prostate cancer. So kidney cancer's a little bit different. There's always trade-offs to each of these kind of management options that I won't go into detail about. But we know that nephron-sparing approaches, we do them because they have less chance of developing chronic kidney disease compared to radical nephrectomy when there is an amenable mass. And this is especially important if patients have any degree of baseline kidney dysfunction to start with or have that risk of going on dialysis already,

There's also one alternative option. I'll mention the standard margin partial nephrectomy, which I also perform due to my training, it's called tumor enucleation. And that's where we can often maximize the preservation of the kidney further by leveraging the tumor pseudocapsule that surrounds it. And that helps us avoid cutting any healthy kidney tissue and avoids placement of compressive sutures most of the time, that can cause ischemia or compression to that remaining part of the kidney, which is what a standard partial nephrectomy does.

Melanie Cole (Host): That was a comprehensive list, Dr. Patel. When you're thinking about active surveillance, is there a way to identify whether it's a benign tumor, whether you're doing biopsy? And you mentioned imaging, because it would seem that information would change your treatment plan. Is there radiologic imaging advances you'd like to discuss? Tell other providers how you know.

Dr Hiten Patel: Yeah, Melanie. So obviously, if we knew a tumor was benign, that would make a big difference in what we recommended for patients and especially with avoidance of surgery. Surveillance, we can do even if the tumor itself is not benign. We can do it for cancers and it's safe for select patients. But especially if it's benign, we would try to avoid morbidity as much as possible. And there's a few things we've learned about identifying patients who have these benign or less aggressive tumors. For most cancers, other urologic cancers, we often obtain biopsy or histologic diagnosis of confirm, "Hey, there really is a cancer before we do the treatment." And we do that for radical prostatectomy for prostate cancer, radical cystectomy for bladder cancer.

Kidney tumors are a little bit unique in that for decades, the vast majority of urologists usually performed a radical or partial nephrectomy without a biopsy. And that means a proportion about 20%, as I mentioned, in that 4-centimeter or less group are going to be benign. And you only find that out after a major surgery. And so the reason for this is our traditional imaging, with ultrasound, CT, MRI are pretty limited in their ability to differentiate what we call a benign renal tumor, the most common of which is an oncocytoma, and also some are called angiomyolipomas, which are completely benign, from malignant ones, which are usually renal cell carcinoma.

And so in our systematic review, we actually found there's a couple predictors of the chance of something being cancer, which is often being male rather than female and having a larger tumor size. But the magnitude of these associations weren't really enough that knowing that alone is going to really change what you're going to do. And so we did a deeper dive into biopsy, because really, well, can we start using biopsy for renal tumors? And we found that it was nearly a hundred percent correct when it showed cancer. But one of the issues was that about 10% to 14% of biopsies actually ended up non-diagnostic. And so at the same time, we could have just not attempted a biopsy and it really didn't change what we did for that 10% to 14% of patients.

And then, for those patients who had no cancer on biopsy, about 70% of the time the biopsy was true, but up to 30% of patients might have actually still harbored renal cell carcinoma, even though that biopsy was negative. And so some tumors may also be in a difficult anatomic location where maybe we can't get a good biopsy. And so if biopsy's not going to change our ultimate management decision, why would we use it? And so what we want is a diagnostic approach that adds something to the decision making process and something that can increase our certainty about telling a patient, "Hey, this looks like a benign tumor." And some of my recent research efforts focus on how to use these novel imaging or unique aspects for our traditional imaging to augment biopsy to maybe together, we can better identify these benign tumors.

Melanie Cole (Host): This is so interesting and so informative for other providers, Dr. Patel. Why don't you tell us about your work on emerging or novel approaches in this area? What are you working on? And while you're telling us, how do you feel that research is going to impact patients as you get into this?

Dr Hiten Patel: So I think, in that augmenting realm that I'm talking about, there's two promising diagnostic approaches for small renal masses. As I mentioned, a central problem with renal mass biopsies is the benign results. And a big contributor here is what we call the finding on pathology of an oncocytic neoplasm. And while we think of oncocytic neoplasm on biopsy as most likely indicating a benign oncocytoma, about 25% may actually be renal cell carcinoma. And it's usually the chromophobia subtype, which can look very similar to oncocytoma when you only sample a little bit of tissue on the biopsy.

But what we found is that a unique feature of oncocytoma is they have a lot of mitochondria. And a study by some of my colleagues at Johns Hopkins found that they actually light up hot or light up brightly on a SPECT-CT scan using a specific tracer that's often used for thyroid in the past, but we're now using for the kidney, 99 Technetium sestamibi tracer. And that demonstrates a lot less uptake when you have cancer, a cold picture because they don't have as many mitochondria. And so that initial data was very interesting and told us that, "Hey, this could serve as a potentially noninvasive biopsy. There's a few cases maybe of renal cell carcinoma where they're hot on the scan and could be missed, because we might think, "Oh, they have a lot of mitochondria. They look like oncocytoma." So I think in my opinion, the best thing to do is to hedge your bets by doing a biopsy on those hot tumors on the SPECT-CT, and that doubly confirms that something's benign. And so we did a detailed cost effectiveness analysis and found that this was a cost effective approach and only left about 0.2% of malignant tumors untreated, and could avoid surgery for over 80% of benign tumors. And so that's one of the two things that I think is very exciting.

The second promising approach that augments biopsy, we really have studied in a biopsy-all setting, so if you're going to biopsy everyone, we can now use this immunohistochemistry for a marker or tyrosine kinase receptor called CD117. And doing that on the biopsy sample, we can then combine it with the measurement on the CT that we call PEER. And PEER is the ratio of the peak enhancement of the tumor to that of the renal cortex. And so using them together is what I think is an exciting approach. So while I mention traditional imaging has limited ability to separate these malignant and benign tumors in the overall population, some of our colleagues at Roswell Park Comprehensive Cancer Center found that this PEER measurement was really able to differentiate those CD117-positive oncocytomas from CD117-positive chromophobe renal cell carcinoma. And this is a distinction we really care about.

We did a validation study of PEER at Loyola University and found the same results with a similar study design. And I think these findings are exciting. So, this second approach or the first approach are really things that can improve our confidence in giving a patient a benign tumor diagnosis. We do need to evaluate these a little bit more prospectively, calculating both of these things on biopsy samples and imaging, but we're already doing that and have studies underway.

Melanie Cole (Host): This is really exciting. So many advancements in your field right now. And if patients are found to have benign tumors and we know they can avoid that morbidity of surgery, as you've just said, are there patients diagnosed or suspected to have actual kidney cancer who can also avoid interventions safely? Speak about that and how that affects the quality of the life of the patient.

Dr Hiten Patel: So, obviously, if we had a benign tumor, it's intuitive that we could follow it and we should try to avoid intervention when possible, but we've learned a lot about, you know, delaying or avoiding surgery altogether for some patients who have these early stage kidney cancers. And so one study, the DISARM study, was a prospective cohort of over 400 patients with these tumors that we placed on active surveillance across a couple institutions. And among other studies, this demonstrated excellent outcomes with several years of followup, five or more years of followup. And over three-fourths of the patients in the study have avoided intervention in this timeframe. So there are triggers to say, "Hey, there's some patients maybe the tumor's growing" or there's issue with the histology that looks more aggressive that we should intervene on. But the majority of patients so far have been able to avoid intervention. And we know selection's important. Patients in the study, they're not everyone who comes in with kidney cancer. They're usually a little bit older patients or patients who have competing risk of death that outweigh the risk of their kidney tumor because the metastatic potential of kidney tumors can be pretty low for small ones. And we've looked at younger subset of these patients and found they can also do very well too. Again, our colleagues at Roswell Park also reported on favorable results when they did an unselected population getting this approach.

And so the main triggers we look for that can help intervene before it impacts the patient's quality of life is tumor growth rate and the absolute tumor size. And so for growth rate, many tumors show very little growth, and that can be encouraging, indicate that, "Hey, this is a tumor we can watch," as long as a patient is comfortable with that. And other tumors may grow quickly and that might lead us to recommend either a biopsy or just intervention at that point.

And so we have evidence that the metastatic potential is very low if your tumor's less than 3 centimeters and still pretty low in the 3 to 4-centimeter range, even though it's not zero. And while more followups going to be important, the data so far show us that patient selecting active surveillance have preserved quality of life and potentially some improvements in mental health. And we've shown slight differences. Maybe that's just because they've become more comfortable with the idea as they've been on surveillance longer and after they select that management approach. And so whether they select active surveillance or treatment, mental health is generally pretty well-preserved.

Melanie Cole (Host): As we wrap up, Dr. Patel, tell us any exciting advanced technologies, protocol, standards, tools, anything you feel is worth mentioning and the key takeaways from this very interesting podcast for other providers.

Dr Hiten Patel: A couple takeaways in the early stage kidney cancer space is that one act of surveillance has become a real option. We use it a lot for prostate cancer, but for select patients, it can be very durable. In terms of technologies, we found new ways to augment biopsy, both with our PEER measurements, as well as a SPECT-CT scan that we've repurposed from using for the thyroid that we can now use for renal tumors.

there are other tracers coming out CA nine and other more kidney cancer, specific tracers that are being Studi. at some institutions and as they pan out and we get better ways of evaluating biopsy tissue, the outlook is only gonna look better for patients here to be able to help them make the correct management decision for their cancer.

Melanie Cole (Host): What a great interview. Thank you so much, Dr. Patel, for joining us today and welcome to Northwestern Medicine. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.