Loading summary
Transcript36 lines
- [00:00]
Unknown Speaker
Foreign.
- [00:10]
Jay Raman
Good evening. My name is Jay Raman and I'm professor of Urology at Penn State Health and chair of the AUA's Office of Education. It's my pleasure to host another episode in our educational podcast series, and this is one of the episodes which really focuses on both new guidelines or in this case, guideline amendments. The specific title is the 2025 Microhematuria Guidelines Amendment. And it's my pleasure to host Dr. Steve Borjian, who's Chair of Urology at Mayo Clinic, and Dr. Dan Baroccas, who's Executive Vice Chair at the Vanderbilt University Medical Center. Dan? Steve, as always, thank you for your time. Delightful to have you on and obviously appreciate the conversation later in the day today.
- [00:57]
Dan Baroccas
Thanks, Jay.
- [00:59]
Unknown Speaker
Thanks. Happy to be here.
- [01:02]
Jay Raman
So, Steve, maybe I'll turn it over to you just as a starting point, obviously, in your role as sort of leadership within the AUA Guidelines Panel and the AUA Guidelines regime, if we want to call it that. But talk a little bit about one of the common questions that comes up, maybe that's relevant to this is how do really guideline amendments go about, you know, when or when is there a consideration that perhaps a guideline should have an amendment, and when is it amended, or when is there a sort of a decision that maybe there's not enough data for a true amendment? Maybe just talk to our listeners about that whole sort of scheme.
- [01:41]
Unknown Speaker
Yeah, no, happy to. Because I think, as you pointed out, it's a very important point to make sure that guidelines stay relevant and they stay contemporary, commensurate with new data that evolves in different topics. So the AUA has a structured process for conducting what are called updated literature reviews, which are essentially assessments of interval data that has been published in manuscript form since a previous release of a guideline. Typically, the AUA process is to do updated literature reviews Somewhere between 24 and 36 months after a guideline is released, and then roughly every 24 months or so after that. The AUA is continuing to recognize that there are certain fields within urology that perhaps data is moving even more quickly with that. Many of the oncology fields, for example, have new release of drugs and treatments more frequently than every 24 months. And so the AUA is gradually moving to a process that's going to allow even more expeditious timeline for that on the order of 12 to 18 months. In terms of how the process of updating a guideline is conducted, an updated literature review is done with a methodologist and the panel chair, as well as two or three other members of a constructed updated literature review panel. The evidence that has been published since the last guideline is then assessed and a decision is made whether to simply update some of the text of the existing guideline if there aren't meaningful changes to statements that would be actionable, that would result from new data, or to conduct, as in the case that we're going to talk about this evening in the microhematur guideline, a true guideline amendment which really involves new actionable statements, new recommendations for healthcare providers to guide evaluation and management of patients. So there is a decision to be made when a literature review is conducted as to whether to stay with just a review or, or to actually move to a formal amendment, as we did here with microhematuria.
- [03:50]
Jay Raman
So Dan, maybe as we sort of delve into microhematuria, obviously this is the third guidelines type iteration, but before we even dive into that, maybe just give our listeners a little bit of a scope of the problem, you know, the extent of it, you know, the background, frankly, why is there even a guideline on microhematuria that the AUA is putting out? Just give us the 20,000 foot view before we talk about some of the nuances of this one.
- [04:18]
Dan Baroccas
No, I think that's an important question. Microhematuria is exceedingly prevalent. If you screen asymptomatic populations, you'll find microscopic hematuria in about six and a half percent on average. But that range is wide depending on what kind of population you're evaluating, what their risk of malignancy and risk factors are. The, the, the microhematuria or hematuria is one of the most common reasons for referral to urology. So it is a huge public health issue. And I think there is and has for a long time been inconsistency in how people are evaluated. And this goes in both directions. There is under evaluation of people who really should get an evaluation. Those are folks who are at high risk for malignancy, but people ignore it or attribute the hematuria to infection arbitrarily or other things like that that fail to properly evaluate them. And then it goes in the other direction as well, where there are these low value evaluations for people with low levels of hematuria who have very few risk factors and where the yield of such an evaluation is extremely low. So not only is it a prevalent problem, but I think the practicing urologist or nurse practitioner has a difficult time sort of deciding, okay, I see there are more than a few red blood cells for a high power field. But what does that mean? What is this patient's risk and what should I do about it? So that's the scope issue. I think that's really important. And in terms of how the AUA has been proactive about this, they had a guideline first there was a white paper way back, but in 2012 there was a guideline published that, that had a one size fits all recommendation. It basically said if you're over the age of 35 and you have more than three red blood cells or greater than or equal to three red blood cells per high powered field on, on a UA with microscopy, that you should undergo a CT urogram and a cystoscopy. And this is a great way of maximizing the detection of urologic cancers and other urologic conditions. However, again, there are people who are really low risk. If you take the whole population of people with microhematuria, the risk of identifying malignancy is somewhere around 3%. But in the people who are non smokers, young people, women, et cetera, that risk is much lower. And so there's a big population that you're over evaluating. Then there are people who are older folks, male, more significant degree of hematuria, smokers who are at higher risk malignancy, where that kind of intensive evaluation is appropriate. So in 2020 the guideline was revised to address that risk difference and make risk based recommendations where we could define a low risk group, an intermediate risk group and a high risk group and make differential recommendations for each of them.
- [08:15]
Jay Raman
So I think you highlighted something that's really important which is, you know, we move from a system which is a everybody gets the same evaluation to 2020. We have now a risk based model that, that was in part, you know, the risk groups were created based upon evidence and data, certain risk factors, tobacco history, maybe gender, age. But at the same time the risk groups had not perhaps been validated or at least investigated to how well are they associated with levels of malignancy and so on and so forth. So maybe I'll sort of use that as a branching point to turn it over to both of you to then say, okay, so we've gone in the right direction. We've gone from we shouldn't evaluate everybody the same way to some sort of risk strata. And I think the theme of this amendment is really refining the risk strata in different ways. So maybe I'll turn it over to both of you to maybe walk our listeners through some of the differences and the nuances of how maybe the risk stratification has been improved over time.
- [09:22]
Dan Baroccas
You know, I think there are some points that are preserved, sort of key principles that thread through each of these iterations of the guidelines. One is that we define microscopic hematuria as greater than or equal to three red blood cells per high powered field. You know, if we go any lower than that, there is no specificity, right? We're picking up everybody. If we go any higher than that, we lose sensitivity for finding important, particularly urothelial cancers. And so that that is preserved. One of the other issues that's preserved is we do recommend an evaluation that, that tries to figure out what are the risk factors for malignancy, but also what are the potential benign causes for the microscopic hematuria. If we think there's a benign cause, we're really obligated to pursue that and get appropriate physical exam and diagnostic tests to prove it. So, for example, if we think it might be a urinary tract infection, order the urine culture and follow that up. If it is in fact an infection, treat it with antibiotics and then repeat the UA after resolution of that. So that we know, was the hematuria based, you know, because of the infection, or was it a separate issue that needs to be investigated? So we retain that, that principle of if you think it's a benign cause, prove that, manage that benign cause, and then repeat your analysis to determine if it, if the hematuria has resolved. Another principle that's retained is the concept of, well, some causes of microscopic hematuria are structural things like malignancy, the things that we urologists detect and treat. Some are medical renal disease, and those are, are implicated by things like high blood pressure, abnormal renal function, casts in the urine, dysmorphic red blood cells, and so forth. And, and so the, the principle is that a patient might have both. Actually, if somebody has these signs and symptoms of medical renal disease, we ought to refer them to a nephrologist, but we also ought to appropriately evaluate them from urologic standpoint, if that's appropriate, then similarly. And finally, those who are on anticoagulation really have a similar risk of detection of malignancy as those who don't take anticoagulation. So we're guided by the AOA guidelines to not to dismiss microscopic hematuria just because somebody is on Xarelto or Coumadin or whatever. We're guided to actually evaluate those patients because the anticoagulation may unmask some underlying urologic pathology. So those are the key things that were retained from one guideline to the next. Steve I don't know if you want to talk about the things that changed that.
- [13:03]
Unknown Speaker
Sure. No. And I very much would echo the importance of the things that you just mentioned in terms of the risk stratified evaluation. So when we think about some of the nuances of what has changed, what's changed when we think first about the low risk patients, an increased appreciation has been, as you brought up, Dan, that there's great heterogeneity in the actual frequency of diagnosis of urologic malignancy in patients with microhematria, and in particular in the patients without any demonstrable risk factors for urothelial malignancy. In younger patients, in women, in non smokers, in those with a lower degree of hematria and a really minimal, if any, smoking history, the risk of malignancy is in the fractions of a percentage. In the fractions of a percentage. So one of the changes in the new guidelines is really to redesignate what was previously just called low risk to now low negligible risk. And it's a subtle wording change, but it does, I think, bring out the really, really limited rate of diagnosis of malignancy in those patients. And then accordingly, the new guideline statement for how do we evaluate a patient that we've now classified as low negligible risk? Suggests that rather than a reflexive evaluation, these patients should be offered a repeat urinalysis within six months. So that's a fairly substantive change, which is to say that patients that have been classified as low negligible risk should not be initially evaluated, but should be reevaluated with a urine analysis within six months and then the next steps guided on the basis of that urine analysis. If that urine analysis does show persistent microscopic hematuria, the guidelines have sort of classified that patient as either intermediate or high risk, depending on the degree of macrohematria at the time of that repeat analysis. And then an evaluation risk based can be done according with an intermediate or a high risk patient. So, so I'd say that's the first of the, the risk categorization, substantive changes that has been made, which is low to low negligible, and a repeat urinalysis rather than reflexive imaging and cystoscopy evaluation in those patients.
- [15:23]
Dan Baroccas
Steve, if I can jump in for a second, this really reflects on, on what I think Jay was saying, or actually you were saying at the beginning, which is that these guideline amendments are based on new evidence that becomes available in the interval between the previous guideline and the next. And, and in this case, there were three key studies that use those 2020 risk stratification system, that risk stratification system, which we based on known risk factors, but hadn't really validated as a constellation of risk factors. And really risk strata. And those studies, each of them showed that these risk stratification, that these risk groups actually defined risk strata with different risk of identification of urothelial malignancy. And so, but what was found obviously is that that low negligible risk really had a tiny risk, as you said, fractions of a percent. And so that justified that change.
- [16:37]
Jay Raman
So, so I think you both said it quite well. So, so the, really, the amendment has really looked at that, that first sort of risk strata, low negligible, and really attempted to decrease and modulate the intensity of the evaluation. It was already not a substantiative evaluation, but even now it has taken it down to something as basic as just repeating the urinalysis and then obviously pivoting at that point if there is persistent microhematuria based upon the extent or the degree of red blood cells. So let's move from the low negligible now. Let's go to the intermediate risk because I think this is perhaps the area where there's the greatest amount of change, mostly, I mean, not mostly, but due to data that has come out. So talk a little bit about intermediate risk, maybe what's the same and then maybe what are some of the nuanced differences and then maybe we'll go to the high risk group and some other future directions.
- [17:45]
Unknown Speaker
Yeah, sure. So the 2020 iteration of the guidelines recommended that we should perform a renal ultrasound and a cystoscopy in patients with intermediate risk microhemature, as you mentioned. I think the most substantive change, again although it's a subtle wording change, is that the guidelines now say that we should recommend, not should perform, but should recommend a cystoscopy and a renal ultrasound for these patients. And the reason for that subtle change is that the guidelines, a new guideline statement has been included in the amendment that states that for patients who have been classified as intermediate risk microhematur, who wish to avoid cystoscopy, which does carry with it discomfort, anxiety, risk of infection, we may offer urine based tumor markers or cytology to help facilitate the decision regarding cystoscopy. So the concept here is that we may obtain a marker and this is the first time that the guidelines have really included this in the initial evaluation of patients previously had not been included as such. And the idea then is that we may add additional risk stratification information. So specifically, for example, if we take a population of patients with each intermediate risk microhematuria in whom the risk of a bladder cancer diagnosis is about 1 to 1.5%, and we use a urine based tumor marker that has a very high negative predictive value and that marker is negative in that patient, we will really drop the likelihood of detecting a bladder cancer to what we would then call a low negligible rate and be able to avoid cystoscopy in that patient. So that's how markers have been introduced. It's very specific. It's an intermediate risk patient who wishes to avoid cystoscopy. You may obtain a tumor marker to allow that shared decision making approach about whether to go forward with cystoscopy. Now, a couple of very important points that the guideline amendment does also include. If you're going to do that in a intermediate risk patient, number one, you should repeat a urine analysis within a year. If you don't get a cystoscopy at the outset, and if a patient has persistent microhematria at that follow up ua, then they should have a cystoscopy. So there's a little bit of a safeguard that's built in. And the second and important point about the evaluation of the intermediate risk patient is that even if you don't do a cystoscopy initially based on the urine tumor marker results, you should do a renal ultrasound. So you should obtain upper tract imaging. And really the marker may allow you to nuance the decision about the cystoscopy.
- [20:38]
Jay Raman
So, Dan, maybe I'll turn it over to you to comment a little bit about a question that comes up often, and it's actually not necessarily a change from 2020 to 2025, but I do think, and there was actually a publication that I saw, I think just today or yesterday about the risks of CT and malignancy and the downstream effect. So maybe just tying in this intermediate picture. Steve talked about markers and that being a potential different way of evaluating these patients to refine your risk stratification even within this subgroup. Let's just talk briefly because I think the other common thread is this concept of ultrasound versus CT or mri, namely ct. Just can you maybe just, you know, highlight some of the data on that? Why ultrasound remains the imaging test of choice here?
- [21:28]
Dan Baroccas
Right. I think the big picture is that CT is superior to renal ultrasound for detection of upper tract urothelial carcinoma. However, upper tract urothelial is really an uncommon malignancy and particularly in the intermediate and low risk groups. The use of CT urogram in those groups is just not cost effective. It's associated with, as you said, the risks of radiation exposure, increased cost, and really negligible probability of increasing sensitivity for identification of a malignancy. Again, because of the rarity, you know, as a result, it really should be used judiciously in those at really highest risk for upper tract urothelial carcinoma. And again, we have made efforts to define and refine that high risk category. Initially, what we said is that this is in the 2020 guideline. We said that people with either greater than 25 red blood cells per high powered field or people greater than 60 years of age, I think that was the criterion. Or people with a history of gross hematuria, people with a smoking history that would exceed 30 pack years. Those folks should be evaluated with cystoscopy and CT urogram. The, the change now in the 2025 guideline, we still recommend a similar evaluation, same evaluation for people in a high risk category. But one of the studies that we talked about that sought to validate the 2020 Risk Stratification System was performed in women alone. It was a retrospective study, but I think it's important in that it showed that women's risk of malignancy in each risk stratum was far lower than what it is in men. And the only women who had malignancy identified were those who had other risk factors other than age, you know, as their risk factors for malignancy. And so what we decided in this iteration of the guideline is that women would no longer be classified as high risk based on their age alone. If you're younger than 60, you're low risk as long as you meet all the other criteria as you're, if you're a woman, if you're greater than 60, you're in that intermediate risk group unless you have high risk characteristics. But the only way women can get into that high risk group is if they have other high risk features. History of gross hematuria greater than 25 red blood cells per high powered field, or that smoking history greater than 30 pack years. And so I think that's another important change that recognizes that women are lower risk, but also should not be dismissed because their risk of mortality, when women are found to have bladder cancer, their risk of mortality is actually higher than men. And in part, that seems to be because people are dismissive of humanitarian women. They say, oh, it's just a uti, it's just this or that. And so those women are turned away or given symptomatic medications and stuff like that instead of undergoing evaluation. So this iteration of the guidelines seeks to further refine that judicious use of evaluation in women.
- [25:40]
Jay Raman
So we talked a little bit about low risk being a negligible risk, who close to, essentially close to zero percent. Just give our listeners, if we get to the intermediate, certain buzz numbers, if we get to the intermediate risk cohort. Just so when you counsel patients in the office, risk of malignancy, ballpark is. What are we looking at in that group?
- [26:02]
Unknown Speaker
Yeah, so the, you know, the chart in the new amendment does give some ranges of the low, negligible, the intermediate, and the higher risk patients. You know, I, I would say that in the intermediate risk patient, it's between 1 and 2%. Dan, I think you, do you think that that's a reasonable thing to just set a ballpark for a patient?
- [26:22]
Dan Baroccas
I think that's right. I, I would say is a wide range because that range includes that study of women where the risk in intermediate risk is quite low. But I think 1 to, you know, 0.5 to 3%, I think 2% is a good ballpark for that, that group.
- [26:43]
Jay Raman
And the high risk.
- [26:46]
Unknown Speaker
Yeah, again, you know, range here because of the number of different features that go into that high risk here, I would say somewhere between 3 and 8% would be a reasonable kind of estimate for high risk patients. Dan, what do you, what do you, what would you say?
- [27:01]
Dan Baroccas
The chart specifically, I just look back, it says 1.33. Again, that's the study with only women to 6.3%. So I think, you know, that that pertains to the old risk stratification system where women could be in that, in that high risk group just because of age. I think if you factor that out, I would say the ballpark is around 5. So what you're talking about is for the low risk, less than 1%, almost zero. For the intermediate risk, 2%, give or take, and for the higher risk, 5%. Roughly. Those are good ballpark numbers.
- [27:39]
Jay Raman
And then, although sort of tangential to today's podcast, but just to close it out, grossi maturia, you know, what are we looking at for malignancy rates for grossi maturia?
- [27:51]
Unknown Speaker
Yeah. So there's a couple of series that have looked at this, and I think very important to know is that patients with gross hematuria are at higher risk for being diagnosed with bladder cancer. Unequivocally, depending on the, on the series that's read, it's upwards of about 10%. But again, still, putting that in context, the most common diagnosis, especially in men, or in particular in men with gross hematuria, remains bph. The vast majority of gross immature patients won't be diagnosed with a malignancy. But important to know that gross hematuria has a significantly higher risk of being diagnosed with bladder cancer than than microhematuria.
- [28:31]
Jay Raman
So coming back to the markers and the cytology question, so low negligible risk, obviously there isn't really a role for these in that setting. Steve, you highlighted very nicely in the intermediate risk group the potential that you may use it in the appropriate person with counseling and shared decision making. So obviously the question is going to be, well, what about the high risk group and where does this fall in? Are there certain scenarios that markers in cytology play a role in this high risk cohort?
- [29:04]
Unknown Speaker
So I would say right now, not in the routine initial evaluation of the high risk patient. And the guidelines are more the low risk or the low risk.
- [29:13]
Jay Raman
Right?
- [29:13]
Unknown Speaker
Yeah. So it really is thread the needle of the intermediate risk patient who's interested in avoiding a cystoscopy can help with shared decision making. You know, as Dan said, not routine in the low risk, not routine in the high risk. Now, and the reason to your question, Jay, about not why not in the high risk? Right now, the thought is that the risk in those patients merits an evaluation with a cystoscopy and upper tract imaging and that those evaluations can't be put off with a marker result. Some of the areas where markers may play a role in high risk patients can be a patient who has persistent microhematuria with irritative symptoms, highly suggestive of cis, for example, in which a marker hasn't been obtained. Patients with equivocal findings on cystoscopy, again, marker may help further inform, may help further inform, but right now, not really a routine place in the high or low risk patient.
- [30:16]
Jay Raman
And so maybe in the last few minutes. So Steve, you walked us very nicely through, you know, every 18 to 24, maybe 36 months we revisit these guidelines, we revisit the data pertaining to the guidelines. And so I. And just as each of these iterations has changed 12 to 20, 20 to 25, maybe walk us through from both your perspectives, what's on the horizon, you know, what might we see in the next four or five years? What may be impactful, that it may be a change or at least an amendment or some modification the next time we have a guideline like this. So I'll turn it over to each of you to give your thoughts.
- [30:57]
Unknown Speaker
Yeah, I Mean so, so in my mind there are two critical areas that, that, that I hope to see and that I anticipate seeing in additional investigation. One is the continued refinement of the risk stratification. We recognize it's still not perfect, it's continuing to get better, it's continuing to be evidence informed. I anticipate as the new risk stratification system gets validated, just as Dan pointed out, there were several validation series in the 2021 we invited. We hope that people will take a shot at these guidelines and see what works, what doesn't work. It'll allow for continued risk stratification, refinement. I anticipate that a part of that may be with additional place for urine markers. As data come out from additional markers or as increased data come out from the existing markers, including from trial studies and things, we may find an additional role for markers in the evaluation of these patients. So that's sort of one broad area that I foresee is continued refinement of the risk stratification. You know, the other one that I hope to see happen is really in what I would kind of broadly call implementation science, which is, you know, how do these guidelines get put into practice? You know, Dan has really published some nice studies on this showing that even when these best of guidelines are constructed, the utilization in clinical practice can be quite low. And we hope that by making the guidelines more user friendly, more judicious, will increase adoption. But it's not only a urology issue. I think we need dissemination of these guidelines to our colleagues in primary care, to our app colleagues, and that's something that I hope to see happen so that when Dan and others look at this practice patterns in years to come, we do see that uptake of guideline based evaluation, concordant care is done. So those are two broad categories of things that I would love to see in our future directions.
- [33:09]
Dan Baroccas
Dan, First I'll say that Steve is a bigger thinker than I am and I'm going to focus on two little wonky, wonky narrow parts. One is that, you know, each lab has its own quirks and how they report hematuria. I'll give an example of our institution says 0 to 4 is normal, yet the guidelines say 3 or more is abnormal. The bigger issue is that a lot of laboratories are converting to automated cell counters and it's not clear how those correlate with the old tried and true. You know, look at a, at a microscope with spun down urine and identify three or more red blood cells per high powered field and So I think it's time to validate and determine what is the true risk of malignancy based on the output of these automated cell counters. And then I think the other issue that we continue to struggle with, and I think this is, you know, every urologist has this issue, okay, the person has microhematurity, I got a negative evaluation. What would do I have to do anything more for this patient? Or how, what if they still have microhematory? Do I have to evaluate them again? And so I think, you know, Mary Beth Westerman did a great job in this rendition of the, of the guideline, refining that follow up plan a little bit and, and determining, okay, you really have a discussion. Do we ever need to look at this again and make that a shared decision making process? But I think essentially we're lacking in data on what does it look like if we let people go after a negative evaluation, what is the probability of ever finding something important if we reevaluate, what's the appropriate interval at which one would reevaluate and so forth. I think right now, appropriately, we're left with our clinical judgment. You know, if you have somebody who's a 70 year old smoker and you didn't find anything, you might want to keep them on the hook and think about reevaluating in two to five years if they still have hematuria, certainly if they have gross hematuria or increasing amounts of microhematuria or new urologic symptoms. But the question really is how do we deal with people after a negative evaluation?
- [35:46]
Jay Raman
You know, that's great, that's great. Well, I, I really appreciate, very thoughtful, very balanced. It's always, it's always a delight to hear you both sort of articulate how to think about it in, in a very practical way. So it's really a pleasure to host both of you. If you'll indulge me for about three minutes now, for our listeners, this is, this is my last podcast for the AUA's Office of Education. It's, it's been a pleasure doing it for the past a little over 150 episodes over four years. And I do want to say a few thanks first. Thanks to our guests. Dan, Steve, obviously it's been my pleasure to host you on my last podcast. But to all of our guests, you know, I, I fully realize that guests that join us do so out of volunteerism, often during the day, at the end of the day, on the weekends, and, and, and it's time and, and I'm always very grateful for the expertise, the conversation. I learned a tremendous amount on these even subject areas I know very little about. I want to thank the AUA staff, Maggie, Katie, and Pat in particular, who have been a part of this podcast journey the last four years at all hours and rescheduling when we have inevitable sort of clinical conflicts and whatnot. And they're really fabulous. And I would say most of all, I want to thank the listeners. You know, when you do these podcasts, you really don't know who's on the other end and whether people are listening or they even appreciate the work. And. And so it has been very meaningful to get texts, emails, direct messages, or even, you know, that perhaps some of the. The biggest flattery is when people come up to you in the annual meeting or even at their boards and tell you how much they use these podcasts as part of their. Their preparation. So for our listeners, it's been really my pleasure to be part of it. There's a big part of me that'll be sad that I won't be doing these in the future, but I'm sure the podcast series will be well situated with Mark Gonzalgo taking over. So, Dan, Steve, my pleasure having you both on my last one. Obviously, we go back many, many years, so I thought it would be a fitting way to finish.
- [38:21]
Unknown Speaker
Well, congrats on a great run, Jay.
- [38:23]
Dan Baroccas
Fantastic. Thank you. And. And yes, congratulations.
- [38:27]
Jay Raman
Thanks so much.
- [38:50]
Dan Baroccas
Sam. Sa.