Read the Full Video Transcript

Zachary Klaassen: Hi. My name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I am delighted to be joined on UroToday by Dr. Phil Pierorazio, who is a urologic oncologist at the University of Pennsylvania and Penn Medicine. Phil, thanks so much for joining us today.

Phillip Pierorazio: Zack, it's always great to share time with you.

Zachary Klaassen: We're going to talk about small renal masses and really just a really high-level view. There's a lot going on in this space. And we see a ton of these patients. So maybe just off the top, at a very high level, what constitutes a small renal mass?

Phillip Pierorazio: Yeah. So the first and easiest way to start with this is—we're going to start at 4 centimeters. The size of a golf ball, really easy for people to conceptualize. Anything bigger than 4 centimeters is not small in the small renal mass space. 4 centimeters or smaller. And these are masses we're really concerned about being renal cell carcinoma. It’s not a cyst. It’s not that fat, rich AML that you know is benign. These are 4 centimeters or smaller and could be a cancer.

Zachary Klaassen: Yeah. No, that's perfect. And I think we're seeing more of these because of increased cross-sectional imaging. And we joke that if you hit the ER with anything, you start off with a CT scan and you go from there. So maybe just discuss how this shift we've seen in the last, say, 10 years and why we're seeing so many more of these small renal masses.

Phillip Pierorazio: Yeah. It's actually a fascinating history. And I'll keep it brief, because I know we don't have hours to discuss this, even though I would like to spend that time with you, Zach. I mean, the trend actually started in the '60s and '70s. And you're right. Cough, sneeze, car accident, CT scan, MRI, ultrasound—and so we saw a lot more renal masses, and the number of these small tumors shot through the roof.

Actually, the last 10 years that number has stabilized. So it's almost like we've saturated the market. But we see 70,000 to 80,000 people per year in the US with kidney cancer. And the vast majority of those, 40-plus thousand, are these small renal masses.

Zachary Klaassen: And the thing is, too—and you see these patients as well. They’re 80 years old. They've got multiple comorbidities. And this will lead into some of our further discussion. But these are not necessarily 45-year-olds that are running marathons. So we have to really figure out what we're going to do about these masses.

So let's transition to you're in the clinic on, let's say, Wednesday. You've got five of these patients in your clinic. Maybe they're new, maybe they're follow up. How are you counseling them on the options? And there's many. I mean, we'll talk about active surveillance, biopsy, growth kinetics, partial nephrectomy, ablation, whichever modality you want to. How are you starting that conversation? And maybe just walk our listeners through each of those modalities.

Phillip Pierorazio: Yeah. So I always start with a brief discussion of biology. And I'm happy to get into more details if you want. But the majority of the conversation is, the majority of these tumors are cancerous, greater than 50% depending on the size, up to 70% to 80% for those 4-centimeter masses.

Of those cancers, very few of them have metastatic potential, meaning even if it is a cancer, it has less than a 1% chance of leaving your kidney. And that takes a lot of the air out of the room. People go, [SIGHS] OK. This is not the end of the world. This is not the big C word I heard of. This is not the pancreatic cancer my friend died of.

So I try and take the wind out of the sails and talk people off the ledge. First thing, this is not going to kill you. Now, we have to discuss how do we want to manage it. And I always start with the most conservative, and I tell them that the most conservative way to manage this is with surveillance. We watch it.

We recognize it has very low ability to spread. This is not going to kill you. And as long as you keep your appointments and we keep an eye on this and it's not growing or causing problems, we can safely watch it. Now, obviously, that conversation is nuanced. Older patient, younger patient, comorbidities, life expectancy, all of that goes into it quickly.

But it always starts with surveillance. And then it goes into the surgical options. And for the vast majority of patients, we're talking about partial nephrectomy. And even for patients with two healthy kidneys, we don't need to remove a kidney for renal masses. And we now have decades worth of literature to show that the oncologic outcomes of a partial nephrectomy are equivalent as long as your margins are clean, which for expert surgeons is not an issue.

Thermal ablation is certainly on the table for patients who don't really want surveillance and don't really want or cannot tolerate general anesthesia for a full intra-abdominal or retroperitoneal surgery. And then I always say the last option is radical nephrectomy. And you're going to find 5% to 10%—10% is probably a little bit high, let's say, 5%—of small renal masses that are just not safely amenable to a partial nephrectomy. And in somebody who's got a healthy kidney on the other side, it's a very reasonable option.

Zachary Klaassen: And when you look at these patients, where does biopsy fit into this armamentarium?

Phillip Pierorazio: Yeah. To be honest with you, it's usually the last part of the conversation. And I say, hey, listen. And if you want some more information, if you want to gather some more data before we make a decision, biopsy is a very reasonable choice. And I think what we've learned over the last 20 years of biopsy evolution is, first of all, it's completely safe. There's no tumor seeding. The risk of bleeding is incredibly low, whether it's a urologist doing it or an interventional radiologist. We're really good at this now.

The issue is still the diagnostic yield. And about 10% of the time, maybe a little bit more, you're not going to get an answer. And even if it finds cancer, it's really only the flip of a coin if it's going to be one of those high-grade or aggressive cancers. So I often tell people, assume this is a cancer. If you know this is a cancer and you want surgery, then just have surgery.

On the flip side, I also say, there's no better biopsy than a partial nephrectomy when it's amenable to that. When you know—you've done hundreds now, Zach. You know when you can do a safe partial nephrectomy. There's no better biopsy than to have the entire mass removed. And, yes, it's two to three hours in the operating room. But you get an answer and you're done.

Zachary Klaassen: You're done. Yeah. And I think too, we're seeing a ton of heterogeneity with biopsies. I mean, there's places that don't biopsy anything. My colleagues in Toronto, Tony Finelli and colleagues, 90% to 95%. And so I think there's a lot of—we could have a whole discussion on just the utility of biopsy, for sure. I'd love for you to walk through, just in general, some of the prognostic factors for small renal masses and maybe how you discuss that with patients, whether it's growth kinetics, et cetera.

Phillip Pierorazio: Yeah. So I tell people the first thing, and I think our most consistent driver here, is tumor size. The bigger a tumor is, the higher the metastatic potential. And if you really look at—there's tons and tons of data now—retrospective, prospective, large institutional, large national, international databases.

Less than 2 centimeters, almost negligible risk of metastatic disease. Between 2 to 3 centimeters, it starts to be about—it approaches 1%. 3 to 4 centimeter range, 1% to 2% chance of metastatic potential. Over 4 centimeters, then you're going to start seeing a real climb. And at about 6 or 7 centimeters, it's about 25%. So that's why we're really honed in on those small renal masses, because we know the metastatic potential is low.

So most people, we set off size cutoffs right when they start surveillance. So, hey, we see you. You're under 2 centimeters. Our conversation is going to change at 2 centimeters. It’s going to change at 3 centimeters. At 4 centimeters, if we're not in the operating room already, we're definitely in the operating room unless there's something that keeps us out.

Growth kinetics—we've learned a lot about in the last years. Our thoughts have changed. Or at least, my thoughts have changed about this a little bit. It’s been one of our traditional markers of biological potential, and I'm not so sure it is anymore. The faster something grows, the more likely it is to get to 3 or 4 centimeters, the more likely we are to go to the operating room. Because the patient gets nervous, I get nervous.

But all of our studies are really not showing that changes any of the biologic or metastatic potential. So I'm not sure what growth rate means under 4 centimeters. I think it means a whole lot over 4 centimeters. So if you have a rapidly growing tumor that you let get bigger than 4 centimeters, you might have an issue there. But I think it's one of the things we certainly measure. It's one of the things we certainly counsel on. But that's important.

And then I think the last, most important one, if you do a biopsy, is that histology. Is it a cancer? What kind of cancer? And we know clear cells can be aggressive. They can also be super indolent. Papillary and chromophobe tend to be indolent across the board. And that helps us make some decisions.

Zachary Klaassen: Yeah. Great answer. Before we jump into some of the cases you're going to share with our listeners, I just want to ask you, in terms of your surveillance, are you doing six months or are you doing alternating CTs, MRIs? What are you doing in your practice?

Phillip Pierorazio: Yeah. So the standard protocol for us is every six months, for two years, annually thereafter. Most patients we are alternating axial imaging and ultrasound. And the reason is ultrasound is a great way to measure a mass when you know where it is, cheap, easy, no radiation. Great way to do it.

That being said, I also tell people this is highly individualized. A younger patient, you may keep a little bit shorter leash on. Somebody with a bigger tumor, if it's 3 and 1/2 centimeters, you may want to see them in three or four months. I don't think we learn a lot in the three or four month range, but it manages anxieties, to be honest with you, your anxieties and the patient's anxieties. And there's nothing wrong with that.

Zachary Klaassen: Totally.

Phillip Pierorazio: And I think that's a very reasonable thing. So that's kind of our brief protocol right now.

Zachary Klaassen: Interestingly, in the last probably two years, I've started doing a little more—at least one MRI at some point. We've got a very good MRI body radiologist who's very accurate. And I think that there's something about maybe those complexes. And we're going to talk about a case with that. If there's some, maybe, delineation needed between a mass versus a complex cyst, the MRI is pretty good. Would you agree?

Phillip Pierorazio: Agree completely. Anytime you see cystic or there's fluid filled, MRI is a great differentiator. And you're right, it's super institutional. And I was at Hopkins for almost 15 years, CT place, CT, CT, CT. So I got really good at reading CT scans. Got to Penn. Penn’s an MRI-heavy place. So I transitioned my practice. And I've learned to read MRIs now.

I actually think there's value in all three of those. The radiologists hate that, when you're comparing cross modality. But I think for a urologist, it's super helpful. You learn different things from a CT scan than you learn from an MRI, than you learn from an ultrasound.

Zachary Klaassen: Without a doubt. Now, I'd love for you to pull up your cases because I think this is really going to help with the conversation as well. So I know you have a couple ready for us.

Phillip Pierorazio: So this is a classic patient, young, 42 years, shows up with a 1-centimeter mass, super healthy, no smoking history, and has an eGFR of greater than 60. And you can see the mass on your different phases of CT imaging there. It's up in the anterior mid pole of the left kidney, and it's small.

I've started calling these indeterminate when they're in that 1-centimeter range. And I think it gives us a new classification or a new category to think about them. At 1 centimeter, the best CT scan, MRI, ultrasound in the world can't tell you what that is. And the statistics change. So for this mass, there's at least a 50% chance that this is benign in a woman this age. But she's here. So what do we do?

So this case is actually a few years old. So because she was so young, this was the time where we're really thinking about genetics and kidney cancer. So she had a whole slew of genetic testing for kidney cancer, and none of it popped up with anything suspicious. So that, once again, lowers your threshold. And this is also at a time where biopsies are getting very sexy for renal masses. So she gets a biopsy, and it shows a grade 1 papillary renal cell carcinoma.

So 1 centimeter papillary—we know indolent. Let's keep an eye on this. And I'll just cut to the chase and show this. This is 10 years later. That mass is still. Look at the y-axis there, 1.3 centimeters over 10 years. So it really has not changed at all. And it speaks to the indolent nature.

So one of the criticisms of surveillance was always you can't do it in young people. And this is just a case, one single case. But our data shows that you actually can do it in young people. And they're slightly more likely to end up at intervention at 10 years. It's about 30% as opposed to 15% in the general population. But that still means 70% of people are out of the operating room.

Now, is this 1-centimeter papillary tumor going to stay centimeter for 40 plus years for her life expectancy? We don't have that answer yet. So she's always going to be on surveillance. But you can see ultrasounds are a great way to measure this. You can mix in MRIs and CT scans. So I think this just brings up the greatest point, that you can watch anybody depending on age and comorbidity, especially if their mass is really small.

Zachary Klaassen: Great case. And it really just goes to the discussion of what our goals are here. We may treat this at some point. We don't have to treat it right now.

Phillip Pierorazio: Exactly. And I have that conversation with people too, is, yes, in your lifetime, is this going to need treatment? Yeah, it probably is. Does it have to happen tomorrow? No. Let's plan this around your life. Do you have a big graduation coming up? You got a family trip. Let's kick it down the road a little bit. It's a kind of a classic line in our world.

But the whole reason we treat cancer is so people can do the things they enjoy doing. And if we're stepping in the way for a 1 centimeter renal mass, we're not doing our job.

Zachary Klaassen: That's right.

Phillip Pierorazio: Good, so here's a second one. And I think it's super common too. This is a little bit of a flip side. This is another 45-year-old, super-healthy woman who now shows up with a report that says 2.8 centimeter Bosniak IV lesion. And Zach, I know you look at a ton of images. I just put one still here. This is not a Bosniak IV lesion. And you can see that right away by looking at this, if you look at a lot of small renal masses and if you look at a lot of axial imaging.

But if you don't, Bosniak IV, you might think, this is indolent. We can watch this. And I think what's really important here is understanding and looking at your own imaging. If you're going to manage a lot of small renal masses, look at your own imaging. Learn how to read them. I think it protects you medico-legally. It helps you make good decisions. And it helps your patients.

This is the thing you see. So this is actually not her first presentation. She showed up, actually, six months later. And it looked like this. So this is where growth rate and size play in. This mass is now 3 and 1/2, almost 4, centimeters. It had a relatively rapid growth rate. This is somebody who needs to be in the operating room relatively quickly. And this is a straightforward robotic partial nephrectomy in an otherwise healthy 45-year-old woman.

Zachary Klaassen: Now I think your point about look at your own imaging is important. I mean, we're not perfect. The radiologists aren't perfect. And it's just a second set of eyes, you get an idea what that geometry looks like on that kidney. How many arteries, how many veins, how close is the pancreas. All these things that if you look at a bunch of these they just intuitively do, right?

Phillip Pierorazio: Right. And people ask me, when we run the quality analysis, how many small renal masses do you need to see? I don't know the exact number. But I think one of the soft rays is if you don't feel comfortable looking at CT scans and MRIs for small renal masses, that's probably the metric that you don't see a ton of them. Send them to somebody who does, whether it's in your practice or the practice across the street. Do the right thing. Send it to somebody who sees a lot.

Zachary Klaassen: Yeah, absolutely.

Phillip Pierorazio: All right. And just one last one. I think it's a really classic case. This is the classic patient, 76 years old, 2.1-centimeter renal mass. If you go back and do that retrospective scope, you go back through the chart, you actually see it was present in 2011, and it was only 1 and 1/2.

This patient actually has early CKD, got a good GFR, but early CKD and a number of medical issues which are not uncommon for men in their 70s. This is what happens to him over the next few years. And sorry, you can't see all of the measurements there. But the thing grows slowly. We actually biopsied it a couple of years later.

It ended up being a grade 2 clear cell renal cell carcinoma on biopsy, relatively high interferometry. And I'll show you the imaging center because it had kind of a hilar tumor. And then you can see the growth curve there. And what made us nervous was right in between 2021 is this jump in growth, where it was stable for a period of time and then jumped up almost half a centimeter to a centimeter in size.

And you'll actually see this with small renal masses. And I think it's one of the misinterpretations of the small renal mass surveillance literature, is that things grow at a millimeter per year on average. So if you take 500,000 patients, which are now in these series, and you average them out, yeah, it's a millimeter per year.

But an individual tumor, an individual patient often does this. It stays quiescent. And then it'll grow in a growth spurt. And so this is what we saw in this patient. And what makes us nervous, and what we're thinking about now, is do multiple successive growth periods make us nervous? But the problem is we're not watching a lot of successive growth periods, because when this happens, this person ends up in the operating room.

So the mass grows, and I'll show you. Let's make sure I can play these videos for you just so you can scroll through these. And here's the MRI. There's your coronal cuts, and you'll see it left endophytic. Definitely, has a central component on the left side. Jumped ahead to the conclusions there. But let's see if I can get this other video to play. Nope.

Well, you can see the still of it there on the axial, where you can see a definite central component. It's in the sinus fat. It's completely endophytic, meaning you're not going to see this on the back border of the kidney. He was a complex patient. He had a lot of questions. But we ultimately decided—I would not argue with someone who did a radical nephrectomy in this setting. But we chose to do a partial nephrectomy.

This is one you want to make sure you have an ultrasound before you go into the operating room to prove that you can find it. But this ended up being a 3 and 1/2-centimeter unclassified renal cell carcinoma, even though our first biopsy showed clear cell. It was low grade, but stage one, and he's actually got a very good prognosis from this. So I think this just shows some of those growth parameters, growth rate changes that you're going to see and how we interpret them in real life.

Zachary Klaassen: Wonderful. Great cases, Phil. So let's fast forward maybe one to three years. If I told you could have another imaging modality, great sensitivity, great specificity, how would this work into your practice? How would you counsel your patients? How often may you use this modality?

Phillip Pierorazio: Yeah. I think that's the big question. And we're in that situation, Zach. We've got a new molecule out, CA9 girentuximab, and a new study, the ZIRCON trial, that actually supports the use of molecular imaging for renal cell carcinoma. So I think, kind of broad strokes, the performance characteristics of this tracer appear to be almost identical to biopsy. But now this is noninvasive.

So, in some ways, this is a game changer, right? You can just set somebody up for, basically, a PET scan for kidney cancer. I'm not going to get into the advanced and staging space. That's not what this conversation is meant for. But in the small renal mass space, it can help us confirm renal cell carcinoma. It's the opposite of that sestamibi that's slowly been picking up to diagnose an oncocytoma or a benign entity.

It's not the easiest test in the world to study. Most PET scans, you get injected and you go right into the scanner. You actually need to get this injection five to seven days before the scan, which makes it a little bit different. But those workflows will get figured out. I think what we need to be careful of is that because this test is going to be easy, our patients are going to want it, we're going to want to learn from it, we don’t creep into the intervention space now.

Oh, you have cancer, you have cancer, where before there was some uncertainty. I don't think we're going to see that in our practice because we tell—excuse me, we tell everybody we watch. Assume you have cancer. Assume this is a cancer, are you comfortable watching it? I think for the growing mass for the patient who's borderline, 3 to 4 centimeters, I think, it's just going to be more diagnostic information. I think it's going to help us make decisions. It's not a perfect test.

Zachary Klaassen: Yeah. Absolutely, well said. Great conversation, Phil, really appreciate your time. Maybe just a couple of quick take home messages for our UroToday listeners?

Phillip Pierorazio: Yeah. So I think the first thing is to recognize small renal masses in general are indolent. And we don't need to be rushing people off to interventions. They may ultimately end there. So start your conversation with a discussion about biology and then progress to treatment. I think a lot of these conversations are more nuanced than the literature lets on, or our guidelines.

Our guidelines say, oh, surveillance, partial nephrectomy, thermal ablation, radical nephrectomy. It is very nuanced. And it's a complex conversation. You're balancing kidney tumor, you're balancing patient, and you're balancing preferences and long-term management. So engage colleagues, engage multidisciplinary conversations. We've got lots of ways to treat these things and manage them. And ultimately, the goal is long, healthy lives for our patients with kidney tumors.

Zachary Klaassen: Yeah. Absolutely, well said. Phil, thanks again. You're an expert in this space. We appreciate your time and your expertise, man.

Phillip Pierorazio: Thanks, Zach. Have a great day.