Podcast Transcript: The Role of Renal Mass Biopsy in Modern Urology

[Dr. Aditya Bagrodia]
It's kind of wild that, once upon a time, kidney cancer was the internist dilemma because there's all these paraneoplastic syndromes, funky manifestations, flank masses, hematuria, and all that kind of stuff. Now it's like everybody and their brother are getting a CT scan. Just baseline, what are we talking here in numbers; common, uncommon, roughly? What's the incidence of kidney cancer, kidney tumors, maybe even smaller kidney tumors?

[Dr. Christopher Anderson]
Fairly common. About 80,000 people a year are diagnosed with renal cell carcinoma. That's based on the most recent SEER statistics for the United States. At least 1 in 40 to 1 in 70 adults will be diagnosed with a kidney cancer during their lifetime, so that's not insignificant. We've seen a substantial increase in incidents of kidney cancer, particularly over the last 30 years. If you look at the curves, there's been this dramatic increase. There's a couple of thoughts about why that is, but probably, for what you've already talked about is that we're doing a lot of cross-sectional imaging.

In the United States, we do tons of scans. We do probably upwards of 80 million CAT scans a year in the United States. In the Medicare population, just shy of 50% of patients will be at risk for having a CAT scan over the next five years. The more we look at people, the more we find. In fact, there's a lot of incidental findings on a CAT scan or an MRI, and the kidney is one of the major ones. About 2% to 3% of CAT scans or MRIs of the abdomen will find something on the kidney. I think that's really led to this huge increase in incidents.

[Dr. Aditya Bagrodia]
I hear you loud and clear. Clearly, there's some consternation that comes along with it until they meet with somebody and hopefully, some of that anxiety is diffused. Maybe just diving on into it, new patient incidentally discovered small renal mass. Let's just hit the highlights on critical elements of history, physical, if there are any critical physical elements that you run through.

[Dr. Christopher Anderson]
Do a full medical surgical history on every patient as you would for anybody. I think family history is really important to learn about whether the relatives have had any cancers, particularly kidney cancers. You're looking for associations with renal cell carcinoma syndromes. Not terribly common, but good to know about. Most of these are not palpable on exam.

I think reviewing their imaging is of critical importance. I rarely rely on a report that describes some sort of suspicious kidney tumor. I usually always want to look at those pictures myself, determine the size, the location, whether it enhances or not. I think a lot of our counseling is based on exactly what a CAT scan or an MRI says, and perhaps the quality of that imaging as well.

[Dr. Aditya Bagrodia]
Obviously, if they're smoking, I think it's a nice opportunity just to plug them into smoking cessation or any of those types of things as a risk factor in addition to the family history. Review the imaging. I'll admit, I love a CAT scan. I love a pre and post-contrast CAT scan. I could wrap my brain around that fairly easily. Then when I look at the MRIs, I generally try to go for the sequences that look most like a CAT scan first.

[Dr. Christopher Anderson]
I'm right with you.

[Dr. Aditya Bagrodia]
Then I'm looking at DWI and the in and out phases. I guess I say this because, of course, as the surgeon in the front line of the disease, we've got to evolve. I also think having a high-quality MRI program and radiologists that you work with is critical.

[Dr. Christopher Anderson]
Fully agree. In fact, we're ordering more and more MRIs to look at kidney tumors. I think that you get more information out of them, and I think our radiologists are able to give us probably better advice about what they think these things are from a radiographic standpoint. No question. Sometimes it's a little bit difficult for me to interpret as well, but I do think that they're very valuable if they can be done correctly.

[Dr. Aditya Bagrodia]
Yes. I feel like I've been able to wrap my brain around prostate MRIs pretty well over my time in this field, but kidney MRIs, I still think there's some learning to be done for me. All right. You've gotten your history, your physical. They've got a small renal mass, which to me is still a quite broad term, 4 centimeters. Is this what you're talking about, right, Chris, 4 centimeters or less?

[Dr. Christopher Anderson]
Yes.

[Dr. Aditya Bagrodia]
My radar for concern at 4 centimeters is quite different from, say, 1.2 centimeters. Let's hear your spiel, if you will, to the patient when they come in with an incidentally discovered mass.

[Dr. Christopher Anderson]
I think this is definitely worth a conversation. A lot of patients get sent in saying, "You have a cancer. You need to see someone immediately to get this removed." Part of the initial conversation is, "Let's slow down a little bit. Let's backtrack just a tad and talk about what exactly are we looking at here. What are some of the numbers, some of the things that we've already discussed."

One thing I'll tell people is that, "Listen, we are diagnosing tens of thousands of small renal masses a year. We've seen this huge incidence in small renal mass, but really, this has not translated to decreases in kidney cancer mortality. There's a possibility that you are here because you've been overdiagnosed with a small mass. Meaning, you have been found to have something that may or may not impact you for the rest of your life."

That's one way to diffuse the tension just a little bit. I do think that's important when appropriate, but then I also talk to patients about, "What could this be?" There's plenty of papers out there that show us among surgically resected renal masses, what are they? For masses that are less than 4 centimeters, about one in five are benign. There's a whole variety of benign masses they can be, and there's a huge prevalence of what are classified as indolent tumors. Meaning, they are cancerous, usually clear cell, but sometimes very histologies that have very low metastatic potential and are very unlikely to cause any harm if possibly left untreated.

We're looking at, among patients with small renal masses, who are the maybe 10% of patients who have aggressive cancers, and could that be you? That's usually where I start the conversation, is to try to diffuse the tension a little bit, give them a little bit more perspective and say, "Listen, most of the time, this is nothing that you need to be urgently worried about."

[Dr. Aditya Bagrodia]
I love that. I'm glad my statistics match with yours. Here's what I do. First day I walk in and say, "You're going to be fine. You're not going to die of kidney cancer. It's not time to get your papers in a fair. You're going to be okay." Then I'll typically say something along the lines of, "If this was 50 years ago, we would've lopped your kidney out. If it was 30 years ago, we would've just removed the spot." These days, we know that so many of these are so benign behaving. I actually borrow a phrase from Scott Eggener's active surveillance counseling, wimpy tumors that almost pose no threat to your life.

Sometimes I'll actually juxtapose it to say, for instance, like pancreatic cancer, esophageal cancer, that are ones that get our attention in a big way. Sometimes tears of joy right there. You can just tell that that was meaningful. I agree. We might get into the incidence of benign tumors in a centimeter, sub-centimeter, 1 to 2 versus 4 centimeters, but 80% of these are going to be cancers. I always say about 90% of those are going to be very benign behaving cancers. I think that math leads to about 10% of these could be real cancer somewhere down the way.

[Dr. Christopher Anderson]
Yes, absolutely.

(2) Risk Stratification and Management Considerations

[Dr. Aditya Bagrodia]
It's a small renal mass imaging. It's got to be what for you? Let's say they had an ultrasound or lumbar spine MRI, what's your initial go-to to really understand it now?

[Dr. Christopher Anderson]
I think, really, the standard is to have some cross-sectional imaging with or without IV contrast. We like to try to use MRI for this. As I said, I think you get maybe a little bit more information to MRI. Obviously, there's no radiation associated with MRI. Some people can't get that, so a CT scan is perfectly acceptable. I'm sure you've seen these patients too who show up with a non-contrast CT with a spot on their kidney, or an ultrasound with a spot on the kidney. You rarely, if ever, want to counsel patients based on that alone. I think it's really important to get the best information you can to really characterize these lesions as best as possible.

[Dr. Aditya Bagrodia]
Unless there's something on a, let's just call it suboptimal imaging modality that's really got my attention, sometimes I'll just try to push that one down four months, for instance. Many times, by the time they got referred, got in, you've ordered the test and completed the test, it's going to be somewhere in that vicinity. Then you already have a little bit of growth kinetics and that type of information.

[Dr. Christopher Anderson]
Yes, I fully agree. I think, just as you had mentioned, stating upfront that, "Listen, there's no urgency here. We have time." Time is often the best gift you can give patients and they thank you for it. It's just saying, "Why don't we check this again in a couple of months?" Very reasonable. I think patients are very receptive to that. You definitely can get some more information out of that, no question.

[Dr. Aditya Bagrodia]
All right. You've counseled them that, again, unless there's something, if it's like a 28-year-old, like a 4-centimeter mass, I'm not going to say, "Hey, let's just keep an eye on this." Understandably, they may be motivated to get something done. Maybe let's talk a little bit about that. When are the small renal masses like, "All right, this is not one to observe and slow play. This one's got my attention"?

[Dr. Christopher Anderson]
That's a great question. I do think, certainly, patient age and longevity have a lot to do with it, but I think there's also a lot we don't know. If you want to draw some parallels with prostate cancer here, we have decades of follow-up for patients with low-grade, untreated prostate cancer, with biopsy-proven untreated prostate cancer. We know that they have a very favorable prognosis. What's the case for untreated biopsy-proven low-grade kidney cancer? We have several active surveillance studies, some of which don't do any biopsies.

I think we have to learn more about the natural history of this disease. Is it appropriate to put a healthy 50-year-old man with a 3-centimeter biopsy-proven oncocytoma on surveillance or a type 1 papillary RCC on surveillance? We think that's probably a non-aggressive cancer, probably poses minimal risk to that patient's life. Is it appropriate to watch that patient? Certainly, there's some unanswered questions there, but it's not obvious that every small renal mass needs treatment. Is age the only factor? Unclear, but certainly plays a major role.

[Dr. Aditya Bagrodia]
All right, so age/patient comorbidity. I think if they have any hereditary cancer predisposition syndromes that are associated with aggressive biology, is that weighing in?

[Dr. Christopher Anderson]
Absolutely. Yes. That would be, for me, a different type of patient. If it was an HLRCC patient, a VHL patient, these ones that you're watching very carefully, you have thresholds for when you might want to consider aggressive treatment. Those, I completely agree. I think probably most of these patients would be the incidental, solitary, small, solid renal mass. Those are the ones who are coming to our clinic most of the time.

[Dr. Aditya Bagrodia]
Assuming in a healthy person, is there a size cutoff where you're more inclined to start the conversation about we're likely going to be treating this versus a size criteria where we'll likely start off with observation and we're going to get to biopsies at some point, which is the focus of this talk?

[Dr. Christopher Anderson]
I don't know. I think it varies a little bit based on age, comorbidity, and so forth. I certainly have patients who are in their mid-80s who are ill who have 6-centimeter tumors that we've been watching for years. Likewise, there's patients who are very young who may not tolerate surveillance for even very small tumors. I do think it's very individualized. I don't think I have a specific cut point, but the bigger they are in general, the higher the risk of an aggressive pathology.

Certainly, there's the patient anxiety that comes into play too. As much as you try to reassure people, knowing that you have a 5-centimeter tumor on your kidney makes you anxious. Some people may or may not want to monitor things depending on how their health is otherwise.

[Dr. Aditya Bagrodia]
I promised myself I'd refrain from any type of generalization than sticking my foot in my mouth. I don't know, this is my gestalt. If it's less than 2 centimeters, I have a hard time signing that person up for any intervention. This, of course, is broad strokes. I think the downside of interval imaging in four to six months, a biopsy is so low. Your likelihood of a missed opportunity of a window for a cure is so low that this is broad strokes. Of course, I want to get your opinion.

Then in a healthy person, 50s, 60s, maybe like hypertension, really as we start getting above 3 centimeters, I'll still try to keep the anxiety level super-duper low. This is extremely manageable. I don't love watching tumors bigger than that. The broad strokes just throwing it out there.

[Dr. Christopher Anderson]
I agree. I think going back to what I was saying earlier, there's a lot we can learn still about how much is size relevant. Is that the only relevant factor? That's something that we can see, we quantify, we follow that. For patients on surveillance, we've learned that rapid growth is bad. Stable growth does not rule out malignancy. How much should we be worried about size alone? I think that's where we probably can get more information on these patients.

There's different ways we can do that. Biopsy is certainly one of them. I think we can probably move towards a smarter algorithm to try to better risk stratify patients compared to looking at your CAT scan and telling you whether or not you should have surgery or surveillance alone.

[Dr. Aditya Bagrodia]
Totally. Totally. Size is obviously variable. There can be periods of no growth and then exponential growth or linear growth. It's impossible to know that with serial scans, but it does impact treatment efficacy, particularly for some of our ablative options.

[Dr. Christopher Anderson]
Absolutely. Yes. Small tumors, usually very, very well suited for ablation depending on the location of the tumor. As they get bigger, ablation is just less effective.

[Dr. Aditya Bagrodia]
Do you have a number in your head where, once they start crossing thresholds, you're like–

[Dr. Christopher Anderson]
Yes. Certainly, the 2 centimeters and less, just like you said, I think that's a great size that's well suited for a successful ablation. There has been effectiveness for larger tumors than that, but very small ones, less than 2 centimeters, almost always effectively ablated.

[Dr. Aditya Bagrodia]
I trained at UT Southwestern and Jeff Cadeddu was a pioneer on RFA. It always seemed that the data suggested after 3 centimeters, you saw a substantial drop-off. That's not like a 90% efficacy versus 50%. It was low 90s down to the 70s. Honestly, that's a little bit tricky. As they started approaching, in my mind, 3 centimeters, do you pull the trigger? Do you continue to watch? Is repeat ablation really that big of a deal? Any thoughts on that, Chris?

[Dr. Christopher Anderson]
That's one of the things that I talk to patients about where we're headed toward some sort of treatment and it's like, "Do I want a surgery? Do I want to avoid surgery with ablation if that's appropriate?" I do tell them that, if you compare surgery compared to ablation, the ability to cure cancers is about the same, although that might require a second ablation in a handful of patients. Some people are very happy to avoid surgery at all costs, even if that means two ablations. Although, for people who want that one-and-done treatment, then surgery probably makes the most sense for them.

(3) Diagnostics and the Evolving Role of Biopsy in Small Renal Masses