BackTable / Urology / Podcast / Transcript #5

Podcast Transcript: Contemporary Medical Management of BPH

with Dr. Claus Roehrborn and Dr. Aditya Bagrodia

In Part I, Dr. Aditya Bagrodia talks with Dr. Claus Roehrborn of UT Southwestern Medical Center about the medical management of benign prostatic hyperplasia (BPH). You can read the full transcript below and listen to this episode here on BackTable.com.

(1) Using the IPSS to Evaluate BPH Symptoms

(2) Lifestyle Modifications Over Medical Management

(3) Pre-Treatment Tests: Flow Rate and Residual Urine Check

(4) Using PSA Test to Estimate Prostate Size

(5) Classes of BPH Medications

(6) Alpha Blockers for Modest-Sized Prostates

(7) 5-ARI Medications for Large Prostates

(8) Anticholinergics and Beta-3 Adrenergic Receptor Agonists for Storage Symptoms

(9) PDE5 Inhibitors for Erectile and Voiding Dysfunctions

(10) Medication Counseling During Follow-Up Visits

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Contemporary Medical Management of BPH with Dr. Claus Roehrborn and Dr. Aditya Bagrodia on the BackTable Urology Podcast)

Ep 5 Contemporary Medical Management of BPH with Dr. Claus Roehrborn and Dr. Aditya Bagrodia

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[Dr. Aditya Bagrodia]
Hello, everyone, and welcome back to the BackTable Urology Podcast, your source for all things urology. You can find all previous episodes of our podcasts on iTunes, Spotify, and at backtable.com.

Today, I'm Aditya Bagrodia, your host from UT Southwestern, and I'm extremely excited to introduce our guest today, Claus Roehrborn, who is the professor and chairman of Urology at UT Southwestern. Honestly, Claus really needs no introduction. He's been a thought leader in the BPH field over the last three to four decades with seminal contributions. So, we're really excited to get his input on practical management of BPH. Welcome, Claus.

[Dr. Claus Roehrborn]
Thank you very much. You make me a little bit older there with the four decades but I'll take it.

(1) Using the IPSS to Evaluate BPH Symptoms

[Dr. Aditya Bagrodia]
Fantastic. Fantastic. So, we'll start out with evaluation. So, tell us a little bit Claus, a patient coming in referred for BPH symptoms, what kind of standard questionnaires, intakes are you using on a routine basis?

[Dr. Claus Roehrborn]
Aditya, the way we should refer to it is really lower urinary tract symptoms. As you know, there has been a long standing debate and BPH is just really a histological diagnosis. And nowadays, the folks who are engaged in BPH management, they refer to it as lower urinary tract symptoms suggestive of BPH. So, men do come in with either storage symptoms or voiding symptoms or a mixture of both. So, they would typically say, "Doc, it bothers me, I get up at night to urinate two or three times, I urinate during the day frequently. If I go to an event, a sports event, or take a trip, I have to stop frequently." Those would be the storage or irritative symptoms. And then some men say, "It's just hard to get the stream started, it's hard to empty my bladder. I feel like I have to strain a lot," and those would be the voiding or obstructive symptoms.

So, for most men, it's a mixture of those symptoms, and they are wonderfully put together in the so-called International Prostate Symptom Score (IPSS) or the AUA symptom score, because it was really developed under the guidance of the AUA in the 1990s. This is a seven-question questionnaire. It ranges from 0 to 35 points, and anybody who would score 7 or less on that score is considered asymptomatic or mildly symptomatic. If you score 8 to 19, you're considered moderately symptomatic, and above that, it's severely symptomatic. This is the A&O, the Alpha and Omega, this is the end and the beginning of all the questionnaires, and it really has set the standard in the assessment of these patients. It's translated and validated in many languages, and that's the score that everybody should use.

[Dr. Aditya Bagrodia]
Okay, good, good. So, everybody's coming in and they're getting an AUA symptom score. So, we've got that bit of information. What other tests are you using at the point of care in the clinic to start your evaluation?

[Dr. Claus Roehrborn]
So, let's just say a man comes in and is bothered by some of these symptoms, my first question would be, what does he score? So, let's just say he scores in the moderate range, 17 points, 18 points, or even more, 20, 22 points. So, I take a look at the score and I initially determine, this is mostly storage symptoms like overactive bladder type symptomatology, frequency, urgency, and nocturia, or is it mostly voiding symptoms? That's my first glance at it.

And then I ask the patient a quality of life question, I asked him, "Just imagine you have these symptoms and you would have to live with those symptoms and there would be nothing that could be done to make them go away, how would you feel about that? Terrible or would you be okay with it, or how would you feel about it?" This single quality of life question sort of sets the stage, because many patients, when they are retired and they score in the lower ranges, they say, "I can live with it, I can make adjustments. I just don't take long trips, or I sit at an aisle seat in a movie theater so I don't bother anybody getting up. I'll adjust to it, I'll adjust my lifestyle." If that's the case, oftentimes I say, "Maybe we don't do anything. Maybe we just monitor it and follow up." Now, other patients will say, "No, this really bothers me. I work. I'm an attorney, I have meetings, I have clients, it's embarrassing. I want something done about it."

So, this single quality of life question is also ingrained into the assessment, and every guideline, the AUA guideline and the EAU guideline have that single quality of life question as part of the initial assessment. And it's really a decision-making split in the algorithm, whether the patient will go for treatment or whether he will go in the direction of active surveillance or watchful waiting. And a lot of people go and just watch and monitor their symptoms because they don't bother enough to actually have a treatment.

(2) Lifestyle Modifications Over Medical Management

[Dr. Aditya Bagrodia]
And in that vein, so lifestyle modifications, anything that you kind of typically try to hammer home with your patients that aren't necessarily looking for medical or surgical management?

[Dr. Claus Roehrborn]
Yeah, exactly. So, let's just say the patient scores 15 points, so it's in a moderate range, and he says, "I can live with this, I can make some adjustment." I say, "Good. Okay, let's talk about that." So, lifestyle modifications take a little time on the part of the physicians, and actually, I'm happy to say that with a new E&M coding system being in place, actually, that's higher valued now, as you know. So, I'll take my time and explain to the patient what he can do. And it's surprising that laypeople often don't have a good understanding of how the urinary tract works, right? They drink water or iced tea, and then they're surprised they have to urinate.

So, you'd have to really start at the beginning and have to say, "Okay, look, now, whatever you drink, 80% of that comes out in the form of urine, some comes out through the skin, some comes out with a bowel movement, but most of it turns into urine an hour or two later. So, you want to watch what you drink and when you drink. So, if you go to a movie, and let's say it's a Titanic--it takes three hours--you're not going to have a 30 ounce glass of iced tea an hour beforehand because that produces a lot of urine. So, if you get up at night a lot, you want to cut down your fluid intake before you go to bed, maybe it's 6:00, maybe at dinner time, cut it in half." So, those are things that people can do easily.

Secondly, many people don't know that coffee and tea are diuretics, as well as just the plain fluid. So, I always tell patients, "Look, when you drink coffee, or tea, or alcohol, it's not just the fluid that that represents--there's a little bit of extra fluid coming out that act as a diuretic, and it makes you urinate faster, so watch out for that."

Then if it's an older man and his bladder may be not quite as good, there is this double voiding technique, and it's really quite effective. I tell the patients a little story, and it's not completely correct, but I tell them a little story. I say, "Look, when you watch the Olympics in the 100 meter dash, what they do is they have endless heats. They have the first, the second, the third heat, but they always have a break so that the same sprinter doesn't have to have one heat, after another, after another, there's two or three hours time. Why is that? The muscles, the sprinter muscle, need to recover."

So, I say, "Think of your bladder as a sprinter muscle. When you void, that muscle expends all of its energy, you have to give it five minutes to rebuild the energy in that muscle and then try to void again. I'll bet you can do more." And that's called double voiding. And double voiding is very effective and getting every bit of urine out. And if you get a lot of urine out and you don't retain, you don't have to urinate as frequently. So, an empty bladder takes a longer time to fill back up and that reduces the frequency of urination both daytime and nighttime. So, those are just some of the few things that people can do, and to most men, they all come as a surprise somehow, it seems so.

[Dr. Aditya Bagrodia]
Yeah, that's sound advice. And maybe I'll ask you to dial in a little bit more on nocturia. Obviously, it's cumbersome, it's bothersome, it impacts rest. Any kind of intervention that you've had that has been pretty reliable for this bothersome problem?

[Dr. Claus Roehrborn]
It's by far the most bothersome symptom and also one of the most common symptoms. So, just by way of definition, the official definition of nocturia is, if a man gets up twice from sleep, goes to urinate and goes back to sleep. So, it does not count the last urination before going to bed and neither does it count the first urination after waking up. So, two times you wake up, you urinate, go back to bed twice. That's nocturia, two or more times.

Now, it turns out that this definition of nocturia applied to the population of men and women is pretty common. For both men and women in their 40s, it increases linearly with age. In their 40s, maybe 10, 15% have it, in their 50s, 20, 25% have it. For men and women in their 60s and 70s, it goes up to over 50%, 60% who have nocturia by that definition.

Now, when you have a patient who claims to have nocturia, you really want to ask him to keep a diary, because many men confuse this last urination before going to bed, the first urination after waking up, so you want to give them a diary and say, "Why don't you just write down when you urinate and when you go to bed, and also if you can, measure how much you'll urinate." So, we give them a graduated cylinder, a plastic cylinder to measure that, so we get an idea how often he gets up at night and how much he urinates. Because that helps to understand, is this just plain frequency at night or nocturia, or maybe it is nocturnal polyuria.

If a man urinates 50% of his total volume at night, more than a liter and a half, that would be nocturnal polyuria, and in my aging male population, often behind that is a little bit of congestive heart failure, right? They deposit fluid in the tissues, at night, when they lay flat, it gets absorbed, and then they excrete it. So, you got to know this, and in order to understand it, a diary or a frequency volume chart is very, very helpful in that setting.

Nocturia is difficult to treat. Neither medications nor surgery are reliable, and the best you can hope for, and it's important to set expectations, is to get a patient down from four episodes to two or from three to one. But to get a 65 year old man to not ever get up at night is just really, really difficult.

(3) Pre-Treatment Tests: Flow Rate and Residual Urine Check

[Dr. Aditya Bagrodia]
Yeah, yeah. Well, that's good to know. I think setting those expectations, because certainly, I've also seen that nocturia is one of the most bothersome issues here.

Let me ask you a quick question, Claus. So, historically, there's these kinds of absolute indications to do something. We've kind of focused on the bother, the quality of life. Historically, these are going to be retention, renal insufficiencies, gross hematuria, UTIs--kind of five traditional absolute indications. What are your thoughts on those?

[Dr. Claus Roehrborn]
To me, they haven't really changed. If a patient is in retention, that would be number one, and he failed two voiding trials with an appropriate trial of an alpha blocker for like three to five days, and he fails a voiding trial again. So, the first time he's in retention would be the first voiding trial, he failed it, the second time he failed it on an alpha blocker, that would be an absolute indication to do something surgically.

A patient who has recurrent urinary tract infection and you looked high and low, and you can't find another cause, no stone, no nothing, then that's another absolute indication. There are some patients, as you know, they have gross hematuria intermittently as a result of just an enlarging prostate, and those stretched out veins, almost like varicose veins, on top of the surface of the prostate. We see them all the time cystoscopically, would be another indication. So, nothing has changed there. Those patients still, in my opinion, have an absolute indication for intervention, except if they are in some way, unable to have an anesthesia, in which case, self-catheterization comes into play.

But before you go into the treatment, I must mention that there are a couple of tests that we like to do and I personally advocate for and the AUA guidelines also advocate for. So, most men cannot really judge the intensity of their stream. You ask them, "Is your stream okay?" And they say, "Yeah, it's fine, I have no problem. It's good." And then you have them do a flow rate, and oftentimes, the urinary flow rate is quite poor. And that's not uncommon. It's just that if a man gets to be 60, 65, 70, and over the years, the flow rate gets slower and slower and slower, the patient doesn't really recognize that as an abnormality. So, I like to do a flow rate test on everybody, and it's really a helpful adjunct test in diagnosing what's going on.

And the flow rate goes hand in hand with a residual urine check. And the residual urine check by ultrasound actually gets a little bit even of a higher priority because we think it's a safety parameter. So, you have the patient do the best he can with a flow rate, you get the peak flow rate as the single best indicator that you get out of the flow rate recording, and then you do the residual urine check, and those numbers you look at. So, if the peak flow rate is about 15 milliliter per second, that's pretty normal for a man in his 60s, and anything above 15 is unlikely to represent obstruction. If the flow rate is under 10 millimeter per second, that's likely to represent an obstructive pattern, at least if you do invasive urodynamics. So, you have already that gradation from 10 to 15 to over 15. And then you look at the residual urine.

So, the residual urine, there's no absolute threshold for surgery indication, but the higher the residual urine, the greater is the risk for retention, the greater is the risk for having frequency and urgency and nocturia, the greater is the risk for having to have something done medically or surgically. Now, many urologists draw the line at 100 CCs, others go to 150, some go to 200. I don't have an absolute line in the sand, but I will say the higher it is, the greater is the risk for all these bad outcomes to occur.

Now, the number of the residual urine also can be put in context with the voided volume, and that's maybe where I do a little bit of head math, and I encourage everybody to do that. Look at the voided volume and look at the residual. If the patient voids 150 CCs, five ounces, and if his residual urine is, let's say, 200 CCs. Well, that's 200 CCs residual of a total of 350, that's more than 50%, and that means their voiding efficiency is only 40%. And that's no good. The voiding efficiency expressed as a percent of the voided volume of the total capacity is a powerful tool for assessment and the judgment in terms of what they need in terms of medical treatment or surgical treatment. The lower the voiding efficiency, the worse the patient's urination is, the more likely it is that he gets into trouble.

It's actually also very simple. Think about it this way. A patient urinates 100 CCs, he retains 200, his voiding efficiency is 100 of 300, that's 30%. So, think about this man's life. He urinates 100 CCs, retains 200, well, an hour and a half later, he's back at 300. That's his capacity. So, he urinates again, 100, retains 200. An hour and a half later or a beer later, there it goes again, he's back up to 300. So, the interval shrinks for him, and frequency and urgency and nocturia are driven by the voiding efficiency. Very powerful tool. And that's why I push for flow rate and PVR measurements in all my patients at the initial visits but also at follow up visits.

So, those are the kind of tools that help me see whether the patient should or shouldn't have treatment. So, it's symptom severity, it's the quality of life--the bother index--and then it's the flow rate and the residual urine and taking some head math to it and calculating the voiding efficiency. And that sets the stage for treatment, oftentimes.

[Dr. Aditya Bagrodia]
Okay. So, a couple of questions. So, urinalysis, urine culture, PSA, that's always kind of a hot one.

[Dr. Claus Roehrborn]
So, the urinalysis is still part and parcel of the AUA guidelines, and if the dipstick shows something, you do a form of urinalysis, or you do an appropriate evaluation. As we all know, the microscopic hematuria guideline was just updated with the help of one of our own faculty, Yair Lotan was involved in that, and it softened the impact a little bit, if you will. Not everybody needs a full evaluation by CT scan, but we do the UA, and if there is hematuria, we go to that evaluation. If it's clean, we'll just go forward. It's part and parcel of it.

(4) Using PSA Test to Estimate Prostate Size

[Dr. Aditya Bagrodia]
Irritative voiding symptoms and smoking history. Are you typically scoping these patients?

[Dr. Claus Roehrborn]
Well, I'm not too keen on doing a lot of cystoscopies in the initial evaluation, and I rely on the microscopic hematuria guidelines by the AUA. They classify patients into higher and lower risk groups, as you know, and it's very useful, and I think it made a big impact because as you know, we just did a lot of cystoscopies and CT uropathies for very few red blood cells with limited yield, right? So, now we eased off a little bit in this categorization.

The PSA is part of the AUA guidelines, is part of the EAU guidelines, and it's just a blessing that the Preventive Services Task Force of the United States government came around to really go and allow the PSA testing again in men between 55 and 70, at least, and so we can extend that a little bit in our older population. So, I like to get a PSA for many reasons. I think it's a good screening test personally, that's my personal opinion and has always been. And secondly, the PSA in a man who has BPH is a indirect measure of prostate size, and that brings us to the third ingredient. We talked about,the subjective symptoms, we talked about the urodynamics, flow rate, and the residual urine, and now let's talk about the organ at the heart of all of this: the prostate-- the size and the shape of the prostate.

So, the PSA, and this was shown by us and by others in the literature, is sort of an indirect marker of the prostate size. Makes sense. Half of the prostate is glandular tissue, the glandular tissue makes the PSA, so the higher the PSA is, the larger is the prostate. And I would say, if a PSA is 1.5 or less, it's a very good guess to say that the prostate is under 30 grams, usually, it's under 30 grams in a man who has BPH. But if it's two or two and a half, the prostate is usually larger, 40 grams, 50 grams, etc. It's a bit of a linear relationship and it's a little bit of a guidance that can help me to judge the prostate size initially.

So, I like to get a PSA and I like to just look at that in the context of my digital rectal examination, which as you know, is notoriously not that accurate. So, I look at the PSA and say, "Well, this is a man who probably has an enlargement or does not have an enlargement of his prostate." So, PSA, I'm in favor of it, except if the patient is really quite old and I see no particular point in it.

[Dr. Aditya Bagrodia]
Okay, good. Good. Now, of course, you can spend hours on PSA, but let's say you've got a 70 year old man, PSA comes back six, and your rectal exam suggests, say, greater than 40, 50 gram prostate, are you okay letting that be or maybe a little hands-on guidance, PSA densities, what are you actually doing to estimate the size of the prostate?

[Dr. Claus Roehrborn]
This conversation can drift a little bit into the PSA territory. I mean, if a patient is 70, has a life expectancy of 16 years by Social Security life tables, with a PSA of 6, I would probably do a multiparametric MRI, and if there's PI-RADS three, four or five lesion, I would probably recommend a biopsy of that lesion. But that's not part of this conversation. Let's just say we did that. Well, we know he doesn't have cancer, so PSA density? I think it's actually in men with pure BPH. It's a fairly reliable indicator of the presence or absence of cancer, because there is that strong correlation between the benign prostate volume, but the question is, how good do you know the volume? So, if you have a patient come in with a high PSA or a patient complaining of voiding symptoms and you have his PSA, should you know the prostate volume? Right? That's kind of the question because otherwise you have no density. That's why the guideline shifted a little bit.

The BPH surgical guideline update 2019 and 2020, updated that chapter a little bit, and I pushed for it on the guideline committee. And it says that a urologist should know the size and shape of the prostate before embarking on invasive therapy and treatment for BPH. And there is really good evidence for it. Think about it. We have the UroLift, we have the Rezum. The UroLift doesn't work as well with patient with intravesical lobes. It is approved from 30 to 100 grams. The Rezum is approved from 30 to 80 grams. A monopolar TURP, you shouldn't do in a prostate where you resect more than an hour, so it shouldn't be done in a patient with a prostate over 80 grams. So, in prostates that are over 100 grams, you're down to basically aquablation, or a HoLEP, or a enucleation procedure, laparoscopic or open. So, the size and the shape of the prostate really, really matters nowadays. It is different when you just have one tool, namely a TURP.

So, that's why the AUA guideline committee pushed a little bit to put the prostate size estimation in front of at least invasive treatments. Since I'm on the guideline committee, I can tell you that in 2021, the AUA guideline medical and surgical BPH guidelines will be blended, and in that blended version, there will be a “could” inserted instead of a “should”. So, it will be as follows. It will say, "If you're thinking about invasive treatment, you should have an imaging of the prostate, either you do an ultrasound, or you already have a cross sectional imaging, an MRI or CT scan. If you have the patient in front of you and you want to give him your best shot for medication, you could think about a prostate size imaging." Not quite the same push here in the guidelines, but the suggestion.

Now, why is that? The reason is pretty obvious. If you have a prostate of 60, 70 grams, the efficacy of the alpha blockers is very limited, right? And if you have a prostate of 20 grams, you shouldn't fool with a 5-ARI, because the 1990s Finasteride studies showed that in prostates under 30 grams, the 5-ARIs act like a placebo, they do nothing. So, there really is good reason to have in these blended guidelines, the recommendation for size and shape assessment also for men with medical treatment. I think this gets us a little bit into the choice of medical therapy. So, I kind of said it already and I let the cat out of the bag. So, the guidelines will push more and more for imaging studies.

[Dr. Claus Roehrborn]
And when I say imaging, I mean mostly TRUS, right, because it gives us size and shape, and when you do a TRUS, you always want to do a sagittal image to look if there is an intravesical protrusion, because that middle lobe changes the entire playing field. Or you have an MRI or a CT scan. Either way, you get the size and shape assessment.

(5) Classes of BPH Medications

[Dr. Aditya Bagrodia]
That's great. That's great. I know that in our clinics here at UT Southwestern, we have very easy to use mobile TRUS sizers, high resolution images, and without a tremendous amount of capital required. So, fantastic.

I think we've fairly extensively covered the evaluation, the non invasive tests, the laboratory tests, how to synthesize PSA, we've talked some about absolute indications, and now we've got a patient that's got symptoms that we've decided merit treatment. Let's just say that we've done a rectal exam, there's nothing to suggest a massive prostate, something kind of standard--30 to 50 grams. Give us just a broad stroke of classes of medications that we're talking about here that are in your arsenal of treatment.

[Dr. Claus Roehrborn]
So, just to step back to the early 1990s when doxazosin and terazosin became available, the first quinazoline derivatives alpha blocker that were approved for the treatment of BPH--really, we should say LUTS--but they were approved for BPH. And then in 1993, finasteride came out, pushed that as a miracle drug that would cure all prostate problems, and we both know that neither one of those things is true.

But from that moment onward, 30 years later, we learned a lot. And I feel the biggest contribution that was made in the field of medical therapy in the last 30 years is to use those drugs in a differentiated manner. So, the classes we're talking about is the alpha-adrenergic receptor blocker, alpha-1 blocker, most specifically, the 5-alpha-reductase inhibitor--the only representatives in the class of hormonal agents--the anticholinergics, and now also the beta-3 adrenergic agonists, that's actually mirabegron and now it's vibegron, a second drug that might be approved for it. And those are the classes of drugs that are available, approved, are able to work alone or in combination, and that's how we have to examine them.

But before we get there, there is one thing, Aditya, we have to mention, and that is a lot of those patients were already in the drugstore, they were already in the supplement store, and they already have Saw Palmetto, Pygeum Africanum, Selenium, you name it, right, these supplements. Comes at 30 to 50 dollar a month, and they ask the same question, "Does it work?" My answer is no, it doesn't work because almost all of them were tested and were found to be no better than placebo in placebo controlled trials. That's specifically true for the most common one, Saw Palmetto. That is the extract of the fruit of the Saw Palmetto tree, which is a dwarf palm tree, it's very common in Florida.

So, I tell my patients, "Those things don't work. If you want to spend the money, that's fine. There are no major side effects, but I would not say they work and I would not recommend them actively."

[Dr. Aditya Bagrodia]
And Claus, obviously, this is your area of expertise, but Cialis, is that still a part of the armamentarium for lower urinary tract symptom management?

[Dr. Claus Roehrborn]
Yeah, I was going to get to that category also, the PDE5 inhibitors, of which there's one drug, namely Cialis, and thanks for reminding me, approved, that will be our additional class.

[Dr. Aditya Bagrodia]
I'm going to just interject real quick. So. I think just to kind of keep it in our brains when we're treating these patients, there's really five class of drugs, alpha blockers, there's the 5-alpha-reductase, there's Anticholinergics, there's beta-3 agonists, there's phosphodiesterase inhibitors, and then maybe we say supplements. It can get overwhelming, but maybe just to make it digestible, I would say that those are going to be our options.

(6) Alpha Blockers for Modest-Sized Prostates

[Dr. Claus Roehrborn]
That's correct. And so, most of the guidelines, they recognize that these drugs have individual strengths, and so globally speaking, it goes a little bit like this. If you have a patient who has a typical mixture of storage and voiding symptoms and you think he has a modest sized prostate, and that's the large majority of all patients interested in drug treatment, they would be best treated with an alpha blocker. And there we have terazosin and doxazosin. The trouble is they require a dose titration and adjustment over time, so it's complicated to prescribe them. And then we have, of course, tamsulosin, which comes in 0.4 or 0.8, then we have alfuzosin as a 10 milligram one dose only, and then we have silodosin, which is either four or eight milligrams.

Now, those drugs have equal efficacy for symptom improvement, and for flow rate improvement, and for quality of life improvement. They do have different side effect profiles, and that's why they all need to be used in a differentiated manner. So, for example, silodosin has the highest alpha-1A specificity and induces anejaculation, and people notice that so you have to tell them. It's about 30% or greater in younger men, and they'll have to know about it. Tamsulosin has the second highest alpha-1A specificity and an ejaculation is as common as perhaps 20%, so people need to know about it.

So, if you have a younger man interested in ejaculation, the silodosin is really a poor choice because they'll call you the next day, they'll complain about it. For a younger man, you want to choose either Flomax, tamsulosin, or alfuzosin, which have no known ejaculation problems because it is not alpha-1A aspecific. It's a single dose, 10 milligrams, and it works just as effectively.

So, it's important to keep these alpha blockers a little bit apart based on the side effect profile. If you have an elderly patient, you don't want to use a drug that has a lot of blood pressure side effects like terazosin and doxazosin. So, there, you go to silodosin. For them, maybe the ejaculation doesn't matter, and silodosin has no effect on blood pressure. It's a pure alpha-1A drug. So, the large group of patients with a modest sized prostate, mixed symptomatology, alpha blockers that I just mentioned would be the number one choice.

[Dr. Aditya Bagrodia]
Okay. And a quick question. I think many of us go reflexively to tamsulosin, which is Flomax. If you're going with one of the other options, any issues or problems with insurance or are these going to be covered first line, no problem?

(7) 5-ARI Medications for Large Prostates

[Dr. Claus Roehrborn]
I think I find that more and more insurances cover alfuzosin without a problem, which is Uroxatral, 12 milligrams, they cover the silodosin or Rapaflo also without any problems. So, I get less and less problems with it nowadays, and there's very few insurances who insist on the old style quinazolines--terazosin, and doxazosin--so it's not very common.

So, if you now go to the next group of patients where you know this is a big prostate, you did a DRE, you think, "Wow, that's pretty large." PSA is, let's say, three. You think, "Wow, that's got to be a big prostate." Those patients can benefit from a 5-ARI. The 5-ARIs are the only drugs that really treat BPH, right? They treat the actual disease, because if you give it, the prostate will shrink by about 25%, the PSA will go down by about 50%, and the actual disease BPH is addressed, and it only works if you give it to men who have a large prostate and it takes time, it takes three to six months to fully take its effect.

So, for that reason, and because the largest studies ever done in our space, that is the MTOPS and CombaT studies, Most cases, if not all cases, the 5-ARI is given together with an alpha blocker. And why? Because you have early on, the symptom improvement from the alpha blocker, and then behind the scenes, so to speak, the 5-ARI addresses the size, the volume issue and shrinks the prostate. And together, they are unbeatable. The MTOPS study and the CombaT study showed that invariably, the combination of an alpha blocker and an 5-ARI is a superior treatment for men with larger glands.

(8) Anticholinergics and Beta-3 Adrenergic Receptor Agonists for Storage Symptoms

[Dr. Claus Roehrborn]
So, if you now move to the next group of patients, those who come in mostly with storage symptoms, and they really have a good flow, but they have frequency, urgency, you've ruled out nocturnal polyuria, congestive heart failure and all the other possible causes, for that you can choose an anticholinergic or a beta-3 adrenergic agonist to treat those symptoms. And that can be done either alone or in combination with an alpha blocker. In practice, the most common scenario is that these patients get an alpha blocker, they are reassessed the months later, they're not happy, and then an anticholinergic is added. That's the add-on therapy. There's a lot of studies that tested the hypothesis and shows it works.

[Dr. Aditya Bagrodia]
Every month, I feel like there's a new study just kind of haranguing anticholinergics in terms of dementia, in terms of the whole myriad of unpleasant downstream effects. Are patients coming to you with these questions?

[Dr. Claus Roehrborn]
Yeah, I think patients do read that, and they are aware of it, and they often ask the question. So, that's why we are trying to lean towards the beta-3 adrenergic agonists, which have a similar efficacy in men as in women. But there is a problem with the insurances, as you know. So, you oftentimes have to try an anticholinergic, and show a side effect, and then you're allowed to switch. So, in practice, it works a little bit like this: You'll give the patient your Ditropan, or your Sanctura, Vesicare, and patient comes back and he says, "I can't take it, I get a dry mouth, I get constipation, I have blurry vision." You say, "Aha, we got a side effect, we're going to switch," and then the insurance covers it. So, you'd have to work around it, and it's a bit labor intensive, admittedly.

[Dr. Aditya Bagrodia]
And are you checking PVRs in these patients pretty routinely at any interval when you start them on anticholinergic?

[Dr. Claus Roehrborn]
I do. Long time ago, I published a study from a data set of a British practitioner, and that data set was amazing. It showed unequivocally that if a man had been given anticholinergics for the indication of LUTS and BPH, that was in the first 30 to 60 days, there was a higher risk of urinary retention. And so I advise anybody who does that to be on the ready and have the patient come back a month later and do a PVR check. And if the PVR goes from 50 to 150, I would say stop it, because that's already trouble in the making. So, there is a higher risk, and I encourage everybody to have a check on the PVR in those patients. That's for beta-3 adrenergic agonists. And I would probably not start it if the residual urine to begin with is very high.

(9) PDE5 Inhibitors for Erectile and Voiding Dysfunctions

[Claus Roehrborn]
That gets us to the last class, you mentioned that yourself, the PDE5 inhibitors, and for practical reasons, only Cialis five milligram is really approved for it as a daily dose, and that has to do with the half life. The other PDE5 inhibitors just don't have a sufficient half life to give a full day's worth of effect, so you would have to take it twice a day. But Cialis, five milligram is around for 24 hours, so you can give it once a day. And it is as effective as an alpha blocker. There was a pivotal randomized trial done in Europe showing that, and it just works as good as an alpha blocker on symptoms and also on the quality of life aspects of it.

The crucial difference is that you want to give that to patients who in that category have both. They have some erectile dysfunction and they have voiding dysfunction. And it makes really good sense to give those patients Cialis because it is just like an alpha blocker for the voiding symptoms, but it also does help for erectile dysfunction. So, globally speaking, you can take patients, categorize them, and allocate them for the best treatment. Alpha blocker alone, 5-ARI plus alpha blocker, anticholinergic or a beta-3 adrenergic agonist plus/minus an alpha blocker, And then the PDE5 inhibitors usually as a mono therapy. But if it's a big prostate, you can couple of them also was the 5-ARI. And those are your classes of medical therapies for your patients to send them out of the door with.

[Dr. Aditya Bagrodia]
Yeah. So, I'll just maybe chime in that I always tell my patients that are receiving Cialis, whether that's for lower urinary tract symptoms or post prostatectomy that good RX is a good option for them to find it as cheaply as possible.

And, Claus, I know this is something that you spent a lot of time thinking about, but the placebo aspect of it, mechanisms of action, Cialis, are you having an improvement in your lower urinary tract symptoms because your sexual health is better? And maybe I'll just kind of throw this out there. Tapering patients off medications, these are men in their 50s and their 60s, are they really ready to sign up for 30, 40 years of medications? Can you just talk a little bit about your counseling, once you've gotten patients on a medication, they're stable? Do you advise them to titrate on, off, increase from 0.4 tamsulosin to 0.8? Maybe just talk a little bit about that aspect of it, please.

(10) Medication Counseling During Follow-Up Visits

[Dr. Claus Roehrborn]
So, the new AUA guidelines that come out this year will for the first time actually offer a look at what to do beyond the first visit. When you look at the guidelines, it's weird, it all talks about what you do the first time you see the patient as if nothing happens afterwards, right? That's how the guidelines are set up in most diseases. So, I've been on this bandwagon for a while and I said, "This is not good enough. We have to tell the practitioner what to do next." And so for the first time, the guidelines have a section on follow up care, and that's exactly what you're asking about.

So, the guidelines will now talk about when to see the patients back, and the recommendation is to see them back a month to three months, and then take a good hard look. Remember, this is perhaps the single most important thing to remember. All studies with medical therapy show about 70% of patients responding favorably. And so I'm asking you, what does that mean? It means 30% don't. So, when patients come back and they're not improved, they still have the same symptom score, I say, "Look, this doesn't work. Why don't we just stop it, reassess, and determine whether you want to go to a minimally invasive surgical treatment or whether you want to live with your symptoms. There's no point in you taking this medication." That's the first major point about this assessment.

Now, if you're on an alpha blocker like Flomax, the FDA and the PDR suggests you double the dose and go 0.4 to 0.8. In silodosin, you go from 4 to 8, you can increase it. Alfuzosin dose increases, there's a glass ceiling, there's no more effect. People ask me about finasteride and dutasteride, there is no effect. You cannot increase the dose because you already have optimum and highest DHT reduction. With the anticholinergics, there is the side effect that limits your dosing, right? There is no more. If you look at mirabegron, 50 milligram already causes blood pressure spikes in some patients, so there's not a whole lot higher dose.

[Dr. Aditya Bagrodia]
And do you ever combine anticholinergic and beta-3 agonists?

[Dr. Claus Roehrborn]
There's studies that have done that and I guess there was some increased efficacy, but that's a costly and side-effect intense combination, and I try to stay away from it.

[Dr. Claus Roehrborn]
The PDE5 inhibitors, we studied that also. Five milligram is it. You don't get more bang for the buck if you take 10 milligrams, and with honestly 20 milligram Cialis daily, there are so many muscle aches, so much back ache, it's not worth it, so I don't recommend that. So, the increased dosing to come up with a better efficacy doesn't always work.

Now, if the patient comes back and you ask this question a month later, and he isn't improved, oftentimes I say, "All right, why might this be?" And that's when I sometimes say, "We should really look at your prostate," if I hadn't done it before, "and visualize it." So, let's say you put a patient on Flomax 0.4, 0.8, he comes back, nothing happens. So, then you do an ultrasound and suddenly you realize he has a posterior intravesical protrusion, it just really bulges into the prostate, into the bladder just like that. So, then I say, "Forget it. This isn't working. You cannot affect this with an alpha blocker, so let's talk about surgical intervention, if you're interested in that."

So, it's at that second stage, that follow up visit, if you think you'll give the patient your best shot, whatever drug it is, you did your best to give him the best treatment for his situation, for his symptoms, for his flow rate, for his residual urine, for his PSA, and if it doesn't work, take a closer look. And oftentimes, that involves imaging at that time, not initially. And so that oftentimes changes the picture completely. Sometimes you see a much bigger prostate than you saw, sometimes you see an intravesical development that doesn't really work well for an alpha blocker or a PDE5 inhibitor, and that changes the playing field and changes the direction quite a bit. And the new guidelines talk about that secondary assessment and how you basically change your algorithm.

[Dr. Aditya Bagrodia]
And on the flip side, so you've got your patient that comes in, 45 years old, you put them on Flomax. "Dr. Roehrborn, this has been an absolute game changer." And you say, "Okay, that's fantastic. We sign up for the next 40 years." How do you advise patients that are actually doing well in terms of quality of life?

[Dr. Claus Roehrborn]
You'd have to advise them, first and foremost, honestly, you have to tell them that, "If you stop the drug, you may do well for a month or two, but the symptoms will come back. There's no question." This has also been studied. There's actually placebo controlled withdrawal studies, okay? Very clever design, and they showed the symptoms come back. So, if you stop an alpha blocker, they come back relatively quickly. If you stop a PDE5 inhibitor, anticholinergic, they come back very quickly. If you stop a 5-ARI, you lost any ground you gained because the prostate grows back. There's two studies that have shown that if you stop a 5-ARI, within a year, the prostate is back to its original size, the symptoms are back, and the PSA is back to where it was before. So, this is a long term commitment for the patient.

Now, there also have been studies done with alpha blockers sort of an on/off, and the patient triggers it themselves. So, when the patient feels he's more symptomatic, let's say in the cold season or whatnot else, with Flomax and silodosin, they can go on and off, they don't have to titrate, that's possible. That has been studied, and people can do it. But by and large, it's a long term commitment, and you have to be honest about that. And if they have side effects and they don't like it, that's probably not going to work, because as you know, the compliance goes way down. If people don't like it because they have side effects, compliance goes down to 50%, 25% in a hurry, and then you might as well not treat it at all.

[Dr. Aditya Bagrodia]
Well, Claus, I think this has been an absolute wealth of information on the evaluation, medical management, and it sets the stage very nicely for a subsequent podcast on BackTable Urology to discuss surgical management. You kind of talked about this earlier on, there's so many different options coming through the pipelines, and really figuring out the best option for the best patient with the best prostate characteristics, it's nuanced and it requires expertise. So, we absolutely thank you again for your information today and look forward to your insights on surgical management.

[Dr. Claus Roehrborn]
Well, thank you very much. It was a pleasure and I look forward to another episode of The Urology BackTable.

Podcast Contributors

Dr. Claus Roehrborn

Dr. Claus Roehrborn is a urologist with UT Southwestern in Dallas, Texas.

Dr. Aditya Bagrodia

Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.

Cite This Podcast

BackTable, LLC (Producer). (2021, April 22). Ep. 5 – Contemporary Medical Management of BPH [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.