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Rashid Rashid Sayyid: Hello everyone, and thank you for joining us in this UroToday recording. I'm Rashid Sayyid, a urologic oncology fellow at the University of Toronto, and along with Zach Klaassen, associate professor and program director at Wellstar MCG Health. We'll be discussing the recently updated AUA guidelines discussing the management of lower urinary tract symptoms attributed to BPH. And in this four-part series, we have been discussing the different segments, and in this series, we'll be delving into the evaluation of patients with BPH. These guidelines, as I previously mentioned, have been updated in 2023 and led by Dr. Jaspreet Sandhu, published in the Journal of Urology earlier this year.

And so in this segment, we'll be discussing the evaluation of BPH patients, specifically those elements pertaining to the initial and follow-up evaluation, the pre-op testing, and the treatment failure rates with the currently available modalities in practice. So starting with the initial and follow-up evaluation, statement number one mentions that in the initial evaluation of patients presenting with bothersome lower urinary tract symptoms possibly attributed to BPH, clinicians should obtain a medical history, conduct a physical exam, utilize the International Prostate Symptom Score (IPSS), and perform a urinalysis. This is a clinical principle. So specifically pertaining to history, important information about medical comorbidities... for example, sleep apnea and diabetes, because we know these can contribute to nocturia in the case of sleep apnea and frequency in the case of poorly controlled diabetes... we should gather information about prior procedures. Is this somebody who has already had treatment for BPH or not?

What is the sexual history? This is particularly relevant given that medication such as alpha blockers have important side effects on ejaculatory function, and we know that TURP has about a 10% risk of ED following that procedure. We also need to discuss the medications that they're on and overall have a discussion about their overall fitness and health. And when we do a urinalysis, essentially what we're trying to do is to rule out a reversible cause of the lower urinary tract symptoms. And so what we're evaluating is for the presence or absence of infection, glucosuria, proteinuria, and hematuria in this setting. What are some optional studies? The PVR post-void residual, so this is a useful test typically done with an ultrasound or a bladder scan that will detect the baseline ability of the bladder to empty and evaluates for retention. And it's important to highlight that there's no predefined value that defines an abnormal PVR, and it varies on a case-by-case basis.

Another optional study is the uroflowmetry whereby patients void into a sensored cylinder and they need to void at least 150 ccs for this to be a valid test. And patients are evaluated for the flow, meaning what is the maximum flow, the average flow, the duration it takes them, also the curve of the flow is important in this setting as well. And so, one of the important variables that are obtained from this test is the flow rate or the Qmax. And we know that a flow rate less than 10 mL per second has quite a significant value in predicting bladder obstruction with a specificity of 70% and a sensitivity of 47%. What's also notable is that treatment failure rates are higher in the absence of obstruction, meaning a Qmax greater than 10 mL per second, which probably suggests that there are other factors in play for these patients.

Another test that could be considered in this setting is a pressure flow study, often called a urodynamics test. But what's important to highlight is that cystoscopy is not indicated as either a mandatory or an optional study in the initial evaluation of patients with LUTS due to BPH. Statement number two states that patients should be counseled on options for intervention, which can include behavior, lifestyle modifications, medical therapy, and/or referral for discussion of procedural options, and this is as an expert opinion. And you may wonder why is a discussion of procedural options stated when these patients are treated by urologists. Well, in fact, these guidelines are also meant for primary care physicians who may be the gatekeepers of this disease and the physicians that these patients see initially and so it's important for them to be involved as well in this entire process. And so they are more than equipped to provide discussions about the behavioral and lifestyle modifications and medical therapy, and the tertiary care comes into play when procedural options are being discussed.

And so, what are some of these modifications? It's important to discuss limiting the intake of fluids prior to bedtime and travel, mild diuretics such as caffeine and alcohol which can make it worse, and bladder irritants such as spicy, acidic food. By limiting these, we can at least eliminate this as a cause of the lower urinary tract symptoms. We also need to discuss other interventions which include regulating bowel movements. Patients with constipation have an increased incidence of lower urinary tract symptoms. Discuss increasing physical activity, weight loss, Kegel exercises at the time of urinary urgency, so essentially learning how to squeeze the pelvic floor muscles at the time of urinary urgency, discuss timed voiding regimens... get ahead of it... and double-voiding techniques as well. Pelvic floor muscle training, including biofeedback, may be helpful for patients with urgency and storage symptoms.

Statement number three in the follow-up evaluation states that patients should be evaluated by their providers 4 to 12 weeks after initiating treatment, obviously provided that adverse events do not require earlier consultation to assess response to therapy. The reevaluation should include the IPSS, and further evaluation may include a post-void residual and uroflowmetry, and this is as a clinical principle. For patients who are started on faster-acting drugs such as alpha blockers, beta-3 agonists like mirabegron, the PDE5 inhibitors such as Cialis, and anticholinergics, these patients probably need earlier follow-up about four weeks given these are fast-acting drugs. Now with the longer-acting drugs such as the 5-ARIs, finasteride, or dutasteride, follow-up within three to six months is recommended given that these drugs take a longer time to exert an effect. And there's no specific threshold for which to look to confirm or reject treatment efficacy, and so we can expect with these medications to see an improvement in the maximum flow by 1 to 5 mL per second.

Patients often do not notice this improvement, and there's no pre-specified targets for IPSS or quality of life improvements, but what we're looking for in this setting is directional improvements. And so, a large magnitude of this IPSS change. So if we take the questionnaire, we'll see a big difference. Typically, this will correspond to a smaller magnitude change in the quality of life. And what's also important to note is that patients with higher baseline IPSS scores, meaning worse symptoms at baseline, require greater drops to achieve similar quality of life improvements compared to those with lower baseline IPSS scores. And this is nicely illustrated in the VA Cooperative 405 study published by Barry, et al., in the Journal of Urology 1995, where we can see in the columns, as we go from the left side to the right side, the baseline IPSS score increases from 12, 16, 20 to 30. And correspondingly to get a very satisfied or satisfied response from treated patients with BPH, we see that we require progressively larger decreases in the IPSS score to achieve the same quality of life benefits.

So again, patients who have worse baseline IPSS scores, worse symptoms at baseline, are going to be more demanding and challenging in practice, requiring a greater mean improvement to derive the same quality of life or perceived improvements. And so, practically speaking, in a clinical situation, the treating physician, along with the patient of course, is going to be faced with one of three scenarios. Either the patient reports that he feels an improvement and is satisfied, he can be neutral as well... and really this is reflected in an IPSS score that's stable... or he may notice a worsening or dissatisfaction. It's really important as well to kind of flesh out the details among these specific patients. So if we look at the left side, among patients who report improvement or satisfaction following treatment, we can notice that the IPSS would've improved at a commensurate level, in which case great, IPSS is improving and they're feeling better and continue the therapy. But we may also notice that either the IPSS has not improved or even gotten worse.

And so this is interesting, patients feel better but objectively they're doing worse. And this may highlight that there are certain symptoms or facets of the disease that bothered them the most, which improved, and that is specifically what drove their quality of life or perceived quality of life benefit. And so it's important again to understand the better we may tailor therapy in this setting. The second scenario where patients report no improvement, the IPSS hasn't really changed, again probably it's a good idea to re-discuss and reassess and offer alternative treatments in this setting. And interestingly, in patients who report worsening and dissatisfaction, we may notice that the IPSS has also deteriorated at a commensurate level, in which case clearly you need to reassess and consider alternative therapy. But conversely, the IPSS may improve or remain stable despite their subjective worsening, in which case again we need to focus on which aspects are bothering them and tailor therapy in a patient-centered approach.

And for statement number four, follow-up evaluation, patients with bothersome LUTS or BPH who elect initial medical management and do not have symptom improvement and/or experience intolerable side effects should undergo further evaluation and consideration of change in medical management or surgical intervention. And this is an expert opinion. And people may ask, "Well, what is an adequate period of initial trial?" And it appears based on expert opinion and clinical expertise that for alpha blockers or PDE5 inhibitors, four weeks is adequate to assess whether this drug is going to work or not. And for 5-ARIs, a longer time of 6 to 12 months for dutasteride or finasteride. And at this point, I'm going to turn it over to Zach to discuss the pre-op testing for these patients with BPH.

Zach Klaassen: Thanks so much, Rashid. So let's talk about pre-op testing for these BPH patients. So this takes us into statement number five, and this is a clinical principle that clinicians should consider assessment of prostate size and shape via transrectal or abdominal ultrasound, cystoscopy, or cross-sectional imaging such as MRI or CT scan, if these studies are available prior to intervention. And this is important because prostate size and morphology may play important roles in the decision-making process as to what technique we use in the surgical procedure. If there's intravesical protrusion, these patients have poor outcomes with watchful waiting and the majority of medical therapies. Minimally invasive approaches may be indicated for prostate sizes such as 30 to 80 grams, but for larger prostates or very large prostates, a TURP or enucleation procedure is likely the best modality to use. What's important to note is that imaging within the preceding 12 months is likely ideal given that prostate growth rate is roughly 1.6% per year. And the formula, which we all know and love, is prostate volume is calculated by height times length by width times PI over six.

With regards to further information on preoperative testing, statement six suggests that clinicians should perform a PVR assessment prior to intervention for LUTS and BPH. A PVR greater than 300 is somewhat considered dangerous and worth monitoring, such as the potential to lead to bladder stones, UTIs, upper urinary tract deterioration, and we should proceed to surgery or formal urodynamic testing for these patients. However, PVR is not a strong predictor of acute urinary retention. Statement seven suggests a clinician should consider uroflowmetry prior to intervention for LUTS or BPH. The minimum voided volume, as Rashid mentioned, is 150 ccs. Patients should be instructed to not use Valsalva maneuvers and this will evaluate the Qmax, the shape of the voiding curve, as well as the duration of voiding.

Statement eight suggests that based on expert opinion, clinicians should consider pressure flow studies prior to intervention for LUTS and BPH when diagnostic uncertainty exists. And so this is to use for definitive evaluation for low detrusor contractility, which is also called the weak bladder, versus bladder outlet obstruction and so we know that this combination of high voiding pressure plus low urinary flow is related to bladder outlet obstruction. And we know that most patients can be managed and treated surgically without pressure flow studies. There's a prior randomized controlled trial comparing routine care to urodynamic testing for LUTS found a similar rate for progression to surgery just over one third for both of these groups of patients in over 820 patients. However, urodynamics is advised in patients with urinary retention, patients with a large bladder diverticulum may have false positive study results so it's important to note this when you're doing your urodynamics testing.

Statement nine is a clinical principle that suggests that clinicians should inform patients of the possibility of treatment failure and the need for additional or secondary treatments when considering surgical and minimally invasive options for LUTS and BPH. And it's important to note that the FDA has no established standardized definition for treatment failure or re-treatment, and this also includes treatment failure for medical therapy as well. And so the remaining slides here, we'll discuss several of the key statistics for each of the treatment failure rates from the procedures that we commonly use in the clinic. So with regards to TURP and transurethral incision of the prostate, or TUIP, the need for a repeat procedure based on data from 10 randomized trials, roughly 800 patients, is a re-treatment rate of 7.2% for TURP. And this may go up to 15% after eight years of follow-up. Whereas for TUIP it's roughly 18.4% needing repeat procedure. In men with smaller prostates less than 30 grams, the long-term need for re-operation is similar between TURP and TUIP at roughly 7.5% within 48 months follow-up.

Looking at TUVP or vaporization of the prostate, there have been six published RCTs comparing TUVP to bipolar TURP, all of these with relatively short follow-up, less than one year. There was a similar need for re-operation with TUVP, a short follow-up and lack of medication reporting basically made it difficult to conclude the long-term efficacy of this procedure, as again mentioning that these are all less than one year of follow-up. Moving on to PVP, this is based on the greenlight laser. We know that older greenlight laser platforms relied on lower powered 80-watt platforms, and they're currently running at right around 180 watts. The GOLIATH study was an international multicenter randomized clinical trial comparing PVP at 180 watts to TURP for men with prostates less than 80 grams, and there was a similar need for re-operation between these two groups. In a recent three-arm randomized clinical trial of PVP versus TURP versus HoLEP in men with prostates 80 to 150 grams, at three years the re-treatment rate for PVP and TURP was 27%, whereas for HoLEP it was only 5%.

Looking at failure rates of prostatic urethral lift, the LIFT study was an international RCT of prostatic urethral lift versus sham in patients with 30 to 80 gram prostates, 140 patients. At five years, 14% required a re-operation for symptom recurrence. 9.3% had their implants removed due to encrustation or implant exposure into the bladder, and 10.7% were on an alpha blocker or 5-ARI. In the prospective BPH6 study, the two-year rate of re-operation in prostatic urethral lift was 13.6% versus 5.7% for TURP. Looking next at water vapor thermal therapy, there has been a double-blind randomized controlled trial looking at water vapor thermal therapy versus sham in 61 patients in the control group versus 135 in the intervention. At four years the re-treatment rate was 9.6%, which also included medical therapy re-initiation. Looking at laser enucleation, this is either HoLEP or ThuLEP enucleation, there were lower rates of re-operation compared to TURP. There was one study reported no re-operations for patients undergoing HoLEP in a pooled analysis of four studies demonstrating lower re-operation risk with a risk ratio of 0.42 for HoLEP, and a subsequent pooled analysis of three studies demonstrated that ThuLEP and TURP had similar re-operation rates with a risk ratio of 1.3.

Moving next to aquablation or robotic water jet ablation, there was a blinded randomized trial of aquablation versus TURP. The three-year surgical re-treatment rate was 4.3% for aquablation versus 1.5% for TURP. All of these re-operations actually recurred within 20 months of the initial surgery. And the three-year medication re-initiation rate was 9% for aquablation compared to 14% for TURP. So this is the AUA sort of workflow when we're looking at the basic management for these patients. So as we've gone through, if patients come in with bothersome LUTS, the recommended tests are to obtain a medical history, perform a physical exam, administer an IPSS score, perform a urinalysis, if available, we should perform a PVR and a uroflowmetry. And then basically, it takes us down a couple of pathways here. So to the far right, if there's no nocturia as a major complaint, we can obtain a frequency volume chart, medication trial, and assess whether symptoms are improving or tolerable. If there's lack of resolution with medication, we can consider other workup and etiology, such as sleep disorders, most commonly sleep apnea.

If we go over to the left side, this is standard treatment. So we always start with lifestyle modifications, and this includes, as Rashid mentioned, caffeine restriction, restricting fluids, contributing medications, assessing what they're taking, discuss lifestyle modifications. Basically, at that point, they can also assess whether these improvements are stable or improved after these modifications. If this is not improved symptoms, then we move on to the bottom left here, which is potential optional tests for evaluation. And this may include a frequency volume chart, another PVR uroflow, urodynamics, or cystoscopy. At that point in time, if it's deemed that they have mainly obstructive symptoms or evidence of bladder outflow obstruction, we should then discuss surgical management with these patients. If it's found that they have an overactive bladder component, then we move on to that set of treatment options. And so I think that's where we really delineate whether this is a bladder issue or potentially a prostate issue.

In conclusion, after initial evaluation, follow-up evaluation should be scheduled based on treatment initiated to assess for symptom resolution. Preoperative testing should include assessment of the prostate size and shape, their PVR, and uroflowmetry. Other evaluations such as urodynamic testing should be handled on a case-by-case basis and particularly relevant if the patient has urinary retention. And finally, treatment failure rates, often compared to TURP, vary widely across studies and treatment modalities. We thank you very much for your attention. We hope you enjoyed this UroToday guideline discussion of the AUA BPH guidelines, specifically looking at evaluation of these patients.