Cheryl Guttman Krader, BS, Pharm

A study investigating the impact of an online patient decision aid on management decisions for benign prostatic hyperplasia (BPH) among men scheduled for a urology consultation at the University of California, Los Angeles Medical Center, demonstrated feasibility of the pre-visit “virtual care” approach as a method for providing patient education, assessing patient goals, and preparing men for a shared decision-making visit with their physician.

The research also showed that the decision aid was well-received by patients as both satisfaction of men who used the tool and their willingness to recommend their physician were very high. In addition, the decision aid was found to reliably identify patients who had been referred to a urologist by their primary care provider without ever having tried medical therapy for BPH. Through responses to items designed to characterize patients’ values and goals for clinical risks and benefits, the decision aid also identified men for whom medication therapy would be an optimal next step, said Christopher S. Saigal, MD, MPH.

The project and its findings were reported in a recently published article.1 Saigal is Professor and Vice Chair of Urology, David Geffen School of Medicine at UCLA, and senior author of the paper. He told 

®, “We found in our study that approximately one-third of men were being avoidably referred by their primary care provider to a urologist for BPH management because the men had never tried alpha-blocker therapy. In communities with limited urologist access and given the projected urology work force shortage, the decision aid could offer an important benefit by identifying patients who could be seen by a practice’s nurse practitioner or physician assistant. This could free up time for the urologist to see more complex patients or those who might need surgery.”

He continued, “The larger message from this study is that I think the future of urology practice will involve leveraging software-based approaches, including decision aids, to improve our ability to manage our large practices in a variety of ways. Done well, such workflows can enhance patient-centered, guideline-concordant care while freeing the clinic encounter to be a place where the high touch ‘art of medicine’ can be practiced.”

English-speaking men ages 18 to 85 years who were scheduled for a new patient visit with a urologist because of BPH were invited to complete the decision aid prior to their appointment. A total of 155 patients with a mean age of approximately 66 years participated in the project.

After their clinic visit, men were asked via telephone survey whether their preferred treatment was with pills/oral medication, procedures (including anesthesia- and office-based), other, or if they were unsure. Only 10 men (6%) self-reported a preference for a BPH procedure, and that rate was significantly lower than in a “usual care” comparator group who did not complete the decision aid.

Analysis of the responses on the completed decision aids also identified 2 distinct groups of men based on their preferences for clinical outcomes such as “importance of symptom improvement” and “importance of avoiding retrograde ejaculation.” Relative to 1 group, the other group of men placed greater emphasis on avoiding sexual dysfunction, dizziness/weakness, and retrograde ejaculation and more importance on BPH symptom improvement.

“Most urologists realize that the constellation of BPH outcomes represent a series of ‘trade-offs’ for patients. We were able to cluster the trade-offs and identify a group that would seem more likely to have a ‘preference match’ for surgery ahead of time,” Saigal said.

“This latter group was small, including only 5 men, but 4 of the 5 men with this preference profile had identified a procedure as their preferred treatment whereas all men who chose medication fell into the other preference profile group. Thus, our study shows that segmentation of patients by preference profile is possible and represents a possible avenue to establish treatment appropriateness.”

Saigal and colleagues have done similar work investigating the impact of a decision aid in men with prostate cancer and are presenting the findings at the American Urological Association annual meeting in September.

1. Sadik JE, Lambrechts S, Kwan L, et al. Management patterns for benign prostatic hyperplasia: impact of a patient decision aid. 

https://doi.org/10.1097/UPJ.0000000000000234

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The research also showed that the decision aid was well-received by patients as both satisfaction of men who used the tool and their willingness to recommend their physician were very high.

Pre-visit BPH decision aid provides valuable insights and optimizes care

Robot-assisted simple prostatectomy (RASP) is associated with superior perioperative outcomes compared with open simple prostatectomy (OSP). The differences might justify the marginally higher hospitalization cost of RASP and even translate into overall total cost savings, concluded investigators who conducted a comparative analysis of the 2 procedures.

For the study, investigators used the National Inpatient Sample (NIS) to identify patients who underwent OSP or RASP for benign prostatic hyperplasia (BPH) between 2013 and 2016. It found that compared with the open procedure, RASP was associated with a shorter median hospital stay (2 days vs 4 days), lower overall complication rate (11.1% vs 29.2%), lower rate of blood transfusion (4.3% vs 16.4%), and a greater likelihood of discharge directly to home rather than to a nursing facility (88.9% vs 76.7%; 

The investigators also found that complications were associated with increased hospitalization cost and greater length of stay (LOS). Despite the shorter LOS and lower perioperative complication rate associated with RASP, total unadjusted hospitalization cost was significantly greater for RASP compared with OSP ($13,467 vs $10,855), likely related to up-front operative costs. Cost analysis performed with a multivariable regression model that adjusted for relevant patient and hospital characteristics found that the robotic approach to simple prostatectomy contributed an additional $6175 to the cost model, whereas the cost of each additional day of hospital stay contributed $1687, suggesting that a reduction in approximately 3 to 4 hospitalization days needed to offset costs associated with the robot system.

“For patients with BPH who have very large prostate glands, surgical intervention is often necessary to improve quality of life and relieve lower urinary tract symptoms when medical therapy fails, said lead author Raj Bhanvadia, MD, PGY3 urology resident at The University of Texas Southwestern Medical Center, in Dallas. “Among surgical options, there is an increased push towards minimally invasive surgery to minimize morbidity to the patient. However, the risks and benefits of utilization of new surgical technology must be carefully considered. Because cost is not the sole factor to consider in the decision about surgical approach, it is an important consideration in justifying additional expenditures associated with the initial investment and maintenance of the robotic system.”

“We believe that if a man cannot undergo or cannot find a center that offers transurethral surgery for large prostate glands, robotic simple prostatectomy is a viable alternative with clinical advantages compared [with] open surgery with a relatively marginal increase in cost,” Bhanvadia added.

The study included 2551 men in the OSP group and 704 men who had a RASP procedure. A comparison of the characteristics of the 2 cohort results showed that the patients undergoing RASP were significantly younger than the patients undergoing OSP (median age 68 vs 71) and significantly more likely to be obese (11.4% vs 7.2%), and significantly more likely to have no comorbidities (23.2% vs 13.5%). In addition to the differences between the 2 cohorts in rates of overall complications and transfusions, the outcomes analyses showed that RASP was associated with significantly lower rates of respiratory complications, ileus or bowel obstruction, sepsis, and genitourinary complications compared with OSP.

Although other studies have shown that RASP is effective and associated with safety advantages compared with OSP, the comparative analysis conducted by the Southwestern Medical School investigators is one of the first to examine surgical outcomes, length of stay, and cost differences between the 2 procedures in a large US-based population.

“Prior cost studies included a mixed group of approaches, including laparoscopic, had relatively small RASP cohorts, or were single centered and had so far produced mixed results. A major strength of our study relative to others in the literature is that it utilizes a large all-payer national population that includes Medicaid and Medicare patients, with a large number of both OSP and RASP patients included. Additionally, many population-based data sets that could analyze outcomes and costs lack data on all insurance types,” said Bhanvadia.

The investigators acknowledged that major limitations of the comparative analysis were that data were not available for comparing the 2 cohorts with respect to prostate gland size. However, the investigators were unable to break down fixed and variable costs, including operative time and the retrospective nature of the study.

But according to Bhanvadia, perhaps its most important limitation is that it does not compare RASP with holmium laser enucleation of the prostate (HoLEP). “Some studies report advantages of HoLEP compared with RASP, but we were not able to identify HoLEP cases in the NIS due to the limitations of existing Current Procedural Terminology coding,” he said. “Additional studies are needed to provide high-quality comparisons between experienced high-volume robotic centers and high-volume centers specializing in HoLEP.”

1. Bhanvadia R, Ashbrook C, Gahan J, et al. Perioperative outcomes and cost of robotic vs open simple prostatectomy in the modern robotic era: results from the National Inpatient Sample. 

Published online September 27, 2020. doi:10.1111/bju.15258

Compared with the open procedure, robot-assisted simple prostatectomy was associated with a shorter median hospital stay.

Benefits of robotic approach to simple prostatectomy may outweigh greater cost

Findings from a double-blind extension study of the vibegron EMPOWUR phase 3 trial demonstrated that once-daily vibegron maintained a favorable safety profile and had durable benefit for improving symptoms of overactive bladder (OAB) over the 52 weeks of the study, exceeding that of the comparator anticholinergic agent, tolterodine extended release.

The data were presented by David Staskin, MD, during the 2020 American Urological Association Virtual Experience.

“Long-term efficacy and safety were investigated as key outcome measures in the extension 

study, and the long-term safety profile demonstrated for vibegron is consistent with the findings in the 12-week placebo-controlled phase 3 study,” said Staskin, associate professor of urology at Tufts University School of Medicine in Boston, Massachusetts.

“The efficacy data from the extension study showed that the benefits of vibegron for reducing average number of daily micturitions, episodes of urge urinary incontinence [UUI], urgency, and total incontinence that were observed at the end of the 12-week pivotal trial were maintained with treatment for up to 52 weeks,” Staskin said. “Furthermore, in post hoc analyses of data from the extension study, vibegron had statistically significant superiority to tolterodine extended-release for reducing UUI and total incontinence episodes.”

Vibegron is a novel ß3-adrenergic receptor agonist. A once-daily dose of vibegron 75 mg was administered in the EMPOWUR phase 3 study (NCT03492281) and the extension study. Notably, vibegron does not inhibit the cytochrome P450 2D6 enzyme (CYP2D6), the hepatic enzyme that is involved in the metabolism of approximately 25% of all drugs. Approximately 43% of patients with OAB take a drug metabolized by CYP2D6.

“Avoiding the potential for drug interactions is especially important in this population, as many OAB patients have comorbidities and take multiple medications,” Staskin said.

Reductions in average daily micturitions seen

Significant reductions in average daily micturitions were seen at week 2 among those taking vibegron, and there was even greater benefit at week 52 in the extension trial, when the mean change from baseline was –2.4. A similar pattern was observed in the analysis of reduction in UUI episodes over time among patients treated with vibegron.

The analysis of change in daily urgency episodes from baseline to week 52 showed a reduction of 3.4 in the vibegron group and 3.2 for tolterodine. At 52 weeks compared with baseline, patients treated with vibegron had 2.5 fewer incontinence episodes daily; daily episodes were reduced by an average of 1.9 in the tolterodine group.

“Post hoc analyses evaluating the difference in week 52 change from baseline between vibegron and tolterodine using the mixed model for repeated measures specified in the statistical analysis plan showed vibegron was statistically superior to tolterodine for reducing both UUI and total incontinence episodes from baseline to week 52,” Staskin said.

Results of a UUI responder analysis of UUI episodes recorded in a 7-day diary showed that 61% of vibegron-treated patients achieved at least a 75% reduction at week 52 and 41% of patients had a 100% reduction: They were dry with no incontinence episodes over the study’s final 7 days.

The phase 3, 12-week, placebo- and active-controlled, double-blind EMPOWUR study randomized 1518 adults with wet or dry OAB to once-daily treatment with vibegron 75 mg, placebo, or tolterodine extended-release 4 mg. EMPOWUR met both coprimary end points, demonstrating statistically significant greater improvement in average number of daily micturitions and UUI episodes with vibegron compared with placebo.

“There was no preplanned statistical comparison between vibegron and tolterodine in EMPOWUR, but numerical differences favoring vibegron were noted in all evaluable efficacy measures,” Staskin said.

In the double-blind extension study, patients originally randomized to vibegron or tolterodine continued the same treatment, and patients in the placebo group were randomized to receive vibegron or tolterodine. The extension study had a target participation of 500 patients. It enrolled 506 patients, and 505 received at least 1 dose of study medication, including 273 who received vibegron and 232 who got tolterodine. The completion rate of patients in the extension trial was approximately 85% and similar across all treatment groups.

Baseline characteristics of participants in the extension trial were similar to those of the EMPOWUR study. They had a median age of 64 years, 78% were women, and 78% had wet OAB.

Adverse events (AEs) were reported by 62.6% of patients receiving vibegron and 54.3% of patients in the tolterodine group. Rates of AE-related discontinuation in the vibegron and tolterodine groups were 1.5% and 3.4%, respectively; rates of treatment-emergent serious AEs were 3.3% and 4.3%, respectively.

AEs reported by more than 5% of patients treated with vibegron included hypertension (8.8%), urinary tract infection (6.6%), and headache (5.5%). The rates of these AEs, including that of hypertension, were similar in the tolterodine group, Staskin reported.

“First demonstrated in the 12-week EMPOWUR study, data from the extension study now confirm efficacy and a very good safety and tolerability profile for vibegron over the 52 weeks of treatment,” Staskin said.

Disclosures: Urovant Sciences provided funding for the study. Staskin is an investigator and consultant for Urovant Sciences and a consultant to Astellas Pharma, Ferring Pharmaceuticals, and New Uro BV.

1. Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd P. Once-daily vibegron 75 mg for overactive bladder (OAB): double-blind 52-week results from an extension study of the international phase 3 trial (EMPOWUR). Paper presented at: 2020 American Urological Association Virtual Experience; June 27-28, 2020.

Beta 3-adrenergic receptor agonist’s benefits observed at 52 weeks, investigators report.

Overactive bladder treatment maintains favorable long-term safety profile

Positron emission tomography (PET) imaging with fluorine 18 (18F)–rhPSMA-7.3 is superior to morphological imaging with computerized tomography (CT) for lymph node (LN) staging in patients with primary intermediate- and high-risk prostate cancer, according to the findings of a retrospective study presented at the 2020 American Urological Association Virtual Experience.

The data from an initial clinical evaluation of the diagnostic efficacy of the investigational radiohybrid 18F-labeled PSMA-7.3 ligand was reported by Tobias Maurer, MD, a urology specialist at the Martini-Klinik prostate cancer center at the University of Hamburg-Eppendorf in Germany.

“68Ga-PSMA PET imaging has become a common method for primary staging of prostate cancer in Europe,” Maurer said. “Although our evaluation of 18F-rhPSMA-7.3 PET imaging is a retrospective analysis, the findings demonstrating its performance are consistent with evidence from studies reporting increased LN detection rates using 68GA-PSMA PET imaging compared with CT.”

Radiohybrid PSMA ligands are a new class of diagnostic/therapeutic PSMA-targeting agents that can be efficiently labeled with 18F. Compared with Ga-labeled PSMA tracers, the 18F-radiohybrid PSMA ligand has several advantages, according to Maurer.

“18F labeled PSMA ligands have a longer half-life, larger batch production, and lower positron range that results in a higher PET image resolution,” he explained. “In addition, radiohybrids have negligible urinary excretion that allows evaluation of the small pelvis without urinary background.”

The first rhPSMA agent evaluated in the clinic, 18F-rhPSMA-7, comprises 4 isomers, and 18F-rhPSMA-7.3 was chosen for clinical development based on findings from preclinical studies. The clinical study investigating the efficacy of 18F-rhPSMA-7.3 PET imaging included 56 consecutive patients with intermediate- or high-risk prostate cancer as defined by the D’Amico risk classification system. All the men underwent the PET imaging and conventional cross-section morphological imaging prior to undergoing radical prostatectomy with a template-based extended LN dissection.

The median injected activity of the tracer was 349 MBq. The median uptake time was 72 minutes, which indicates that the procedure could be nicely integrated in the clinical workflow, Maurer told 

The median number of LNs removed per patient was 21. On pathology, 18 patients (32%) had metastases, of whom 15 had pelvic LN metastases and 3 had bone metastases. The number of pelvic LN metastases present per patient ranged up to 19, and the metastases were located in 33 of 319 templates (10.3%).

The presence of LN metastases on imaging was done by an experienced reader independently for the PET and morphological data sets. The diagnostic accuracy of the 2 imaging techniques was determined by comparing their results to histological findings in template-based, patient-based, and side-based (right/left) analyses.

In all 3 analyses, 18F-rhPSMA-7.3 PET imaging demonstrated statistically significant superiority to conventional CT imaging for detecting LN metastases. The values for area under the receiver operating characteristic curve for 18F-rhPSMA-7.3 PET imaging and CT were 0.842 and 0.697, respectively, for the patient-based analysis (

 < .05); 0.843 and 0.631, respectively, for the right/left-based analysis (

 < .001); and 0.801 and 0.639, respectively, for the template-based analysis (

Disclosure: Blue Earth Diagnostics Ltd provided funding for the study.

1. Maurer T, Langbein T, Kroenke M, et al. Diagnostic efficacy of 18F-rhPSMA-7.3 imaging for N-staging patients with high-risk prostate cancer. Paper presented at: 2020 American Urological Association Virtual Experience. Abstract MP62-17

Agent shows statistically significant superiority to conventional computed tomography.

Cheryl Guttman Krader, BS, Pharm

Articles

Pre-visit BPH decision aid provides valuable insights and optimizes care

Benefits of robotic approach to simple prostatectomy may outweigh greater cost

Overactive bladder treatment maintains favorable long-term safety profile

PET imaging agent found superior to CT for lymph node staging in prostate cancer