Cheryl Guttman Krader, BS, Pharm

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

The Michigan Urological Surgery Improvement Collaborative (MUSIC) sought to provide insight on stent use following ureteroscopy and its impact on unplanned health care use.

The recent analysis included ureteroscopic procedures for urinary stone disease from the MUSIC Reducing Operative Complications from Kidney Stones (ROCKS) clinical registry. It found that stent placement after ureteroscopy was common, varied substantially across urologists as well as practices, was associated with certain demographic and clinical characteristics, and increased the likelihood of a postoperative emergency department (ED) visit.

Spencer C. Hiller, MD, Endourology Fellow at the University of Michigan in Ann Arbor, presented the findings on behalf of his MUSIC colleagues. Hiller said, “It is common practice to place a ureteral stent after ureteroscopy for urinary stone disease.

“Several studies have demonstrated that stents are associated with patient discomfort, but the impact of stent placement on unplanned health care utilization is less clear,” added Hiller, working with Casey Dauw, MD, and colleagues.

The study, presented at the 2020 American Urological Association Virtual Experience1 included all patients who underwent primary ureteroscopy for urolithiasis from June 2016 to May 2019 in the MUSIC ROCKS clinical registry. After excluding urologists and practices with fewer than 10 ureteroscopies during the study period and patients having a second- look ureteroscopy, bilateral procedure, or with stones measuring greater than 2 cm, investigators identified 9662 procedures performed by 137 urologists representing 24 separate practices across the state of Michigan. Both academic and private practices, including group and solo practices, were represented.

Overall, a stent was placed following ureteroscopy in 73% of procedures, but the utilization rate ranged from 11% to 100% among providers and from 34% to 100% among practices. Investigators saw profound variation in stent use irrespective of case volume, even among urologists within individual group practices.

Bivariate and multivariate analyses were carried out to identify demographic and clinical characteristics associated with stent placement. Findings of the logistic regression analysis showed that the likelihood of stent placement decreased by 75% when a ureteral stent was present prior to ureteroscopy and by 31% in cases with a renal stone location. The likelihood of stent use increased by 5.43-fold in cases with ureteral access sheath use.

Increasing age was also a risk factor for stent placement. Relative to cases with a stone measuring 5 mm or less, stones larger than 5 mm to 10 mm were associated with a 1.89-fold increased risk of stent placement, and 4.68-fold in cases with stones larger than 10 mm.

In a bivariate analysis, the use of a stent after ureteroscopy was associated with a statistically significant increase in the rate of both ED visits and hospitalizations. The ED visit rate was 8.5% in cases where a stent was placed versus 7.1% where a stent was not used (

 = .018), and the hospitalization rate was 3.8% for cases with a stent versus 2.9% for cases without a stent (

In a multivariable logistic regression analysis, controlling for patient and stone factors along with surgeon and practice variation, stent placement was associated with a statistically significant, 25% increased likelihood of an ED visit. However, there was no longer a statistically significant association between stent placement risk of hospitalization.

Hiller concluded, “Because of our finding that patients with a stent are more likely to have an ED visit, we recommend that efforts should be made to identify patients suitable for stent omission in order to decrease these unplanned health encounters.”

1. Hiller S, Swarna K, Slayton J et al. Ureteral Stent Placement Following Ureteroscopy Increases Emergency Department Visits in a Statewide Quality Improvement Initiative. Presented at: 2020 AUA Virtual Experience. Abstract PD01-09.

Articles

Study results show wide variation in stent placement following ureteroscopy.

Patients undergoing post-URS stent placement more likely to visit ED

Analyses of data from prospective follow-up of more than 3800 men show that photoselective vaporization of the prostate (PVP) with a proprietary laser system (GreenLight XPS) is a safe and durably effective procedure for treating lower urinary tract symptoms related to benign prostatic hyperplasia (BPH), said Kevin Zorn, MD.

At the 2020 American Urological Association Virtual Experience, Zorn presented findings on behalf of coinvestigators in the global GreenLight Group, which is comprised of 8 expert surgeons practicing at 7 international referral centers1. He reported that the procedure was completed using just a single fiber in 92.5% of men; resulted in a prostate-specific antigen (PSA) reduction of 53.5% at 24 months, which was comparable to that achieved with other treatments for BPH; and was associated with few major complications. Furthermore, during follow-up of up to 5 years, only 1.5% of men underwent repeat surgical intervention for BPH recurrence.

“There has been accumulating evidence in the literature demonstrating the long-term durability of GreenLight PVP. To our knowledge, our multi-institution, multi-user study is the largest collective experience with this treatment modality,” said Zorn, a professor of urology at theUniversity of Montreal (CHUM) in Quebec, Canada.

The men included in the study were treated with the XPS 180W system between 2011 and 2019. They had a median age of 70 years and a median prostate volume of 65 mL as measured by transrectal ultrasound. Median lobe presence was observed in 36.5% of men, 35% had a Foley catheter preoperatively for urinary retention, and 34% were on anticoagulant therapy other than aspirin.

Median operative time was 62 minutes and median energy used totaled 250 kJ, corresponding to an energy density of 3.9 kJ/mL prostate volume.

“The operative characteristics in this population were typical of what we would expect with this procedure. Operating time tends to average 1 min per mL of prostate volume, and energy use typically ranges from 3 to 4 kJ per mL,” Zorn said.

The perioperative transfusion rate was only 0.8% and the median hospital stay was 2 days.

“It is important to recognize that several of the participating centers were in Europe, where surgeons are obliged to keep patients in the hospital for at least 2 or 3 days because of criteria for reimbursement,” Zorn said.

Median duration of Foley catheterization was 1 day or less in approximately two-thirds of men, and 5.9% of men required recatheterization, which is consistent with other large BPH series, according to Zorn.

Incidental prostate cancer was observed in final surgical pathology in less than 2% of men. Thirteen percent of men were readmitted to the hospital within 30 days, and most of them were on anticoagulant therapy.

Postoperative adverse events (AEs) occurring within 30 days after the procedure were categorized using the Clavien-Dindo classification system. Most were minor (grades 1-2), with the most common being lower urinary tract symptoms (22.3%), incontinence (10.4%), hematuria (9.9%), and retention (7.4%). The most common major AEs (grades 3-5) were retrograde ejaculation (4.4%) and postoperative transfusion (1.3%). All other major AEs occurred at a rate of 0.8% or lower.

“The lower urinary tract symptoms were mainly managed with anticholinergics; retention occurred mostly in men who were in retention preoperatively, and most cases of hematuria were managed with hydration without need for hospitalization or a return to the OR,” Zorn stated.

Functional outcomes analyses showed that median PSA was decreased by about 50% throughout follow-up to 5 years. Median International Prostate Symptom Score was 22 at baseline and remained at 4 or 5 between 6 months and 5 years. Median peak flow rate decreased from 6.3 mL/s at baseline to 17 mL/s at last follow-up, and median postvoid residual volume decreased from 122 mL at baseline to 23.5 mL at 5 years.

Discussing limitations of the global retrospective study, Zorn mentioned that because of its global nature and retrospective design, it is difficult to account for variations between surgeons in preoperative medical therapy and skill. In addition, many of the patients returned to their referring urologist after their procedure, so follow-up data needed to be obtained via phone contact.

Disclosures: Dr Zorn is a paid consultant and proctor surgical trainer for Greenlight PVP and Rezum by BSCI (Boston Scientific), an investigator and paid consultant for Procept BioRobotics for Aquablation, and investigator for Zenflow and Urotronic BPH treatments.

1. Law K, Tholomier C, Couture F et al. Global GreenLight Group: Largest International GreenLight Experience for Benign Prostatic Hyperplasia. Presented at: AUA 2020 Virtual Experience. Abstract PD61-07.

Only 1.5% of patients undergo repeat surgical intervention for BPH recurrence.

Photoselective vaporization of the prostate found safe, durably effective

New data from phase 3 clinical trials provide further evidence supporting the safety and effectiveness of the first-to-market oral testosterone undecanoate treatment for hypogonadism (Jatenzo), reported Stanton Honig, MD.

Honig presented results for secondary end points from 2 randomized studies comparing the lipoprotein-coated testosterone undecanoate formulation with topical testosterone treatments showing that both the oral and gel products were associated with statistically significant improvements in psychosocial well-being and bone and body composition parameters. Safety analyses showed the oral testosterone undecanoate was associated with a modest increase in blood pressure, which was slightly higher in men with hypertension at study entry than in men with normal blood pressure and that neither the oral nor gel testosterones had any significant effect on liver function test results.

“This novel formulation of testosterone undecanoate is a first-in-class oral testosterone replacement that does not have liver issues,” said Honig, professor of clinical urology and director, Men’s Health, Yale University School of Medicine, New Haven, Connecticut.

“Taken twice daily, it provides hypogonadal men with total testosterone concentrations in the mid-eugonadal range. Its safety profile is generally consistent with injectable and topical testosterone preparations, although the product labeling for oral testosterone undecanoate includes a black box warning about the potential for increased blood pressure. The data collected in the oral testosterone undecanoate studies underscore the need to check blood pressure at some point in men who are started on this therapy, especially those who are hypertensive at baseline.”

The 2 trials comprised a 4-month study and a 12-month investigation. Eligibility criteria were similar in the 2 trials. Men ages 18 to 65 years (to 75 years in the 12-month study) were included if they had hypogonadism (serum testosterone <300 ng/dL on 2 morning samples approximately 7 days apart), had signs and symptoms consistent with hypogonadism, and were either naive to or underwent washout from testosterone therapy.

The 4-month study randomized 222 men 3:1 to oral testosterone undecanoate 237 mg twice daily or once-daily topical testosterone solution. A total of 325 men were randomized 1:1 to oral testosterone undecanoate 200 mg twice daily or topical testosterone gel in the 12-month trial. Dose adjustments were allowed based on serum testosterone levels.

The 4 treatment groups were similar with respect to demographics and clinical characteristics in terms of baseline age, body mass index, comorbidities (prediabetes, diabetes, and hypertension), and mean baseline testosterone levels. Time-weighted average testosterone concentration increased to reach mid-eugonadal levels in all 4 treatment groups, with values ranging from 425 ng/dL to 524 ng/dL across all 4 study groups.

Data on psychosocial well-being were collected in both trials using the Psychosexual Daily Questionnaire. Results showed statistically significant improvements from baseline to study completion in mood, sexual desire, weekly sexual activity, and sexual energy with and without a partner with both the oral and topical treatments, Honig reported.

General well-being was evaluated in the 12-month study using the 36-Item Short Form Health Survey questionnaire. In the individual domains, statistically significant improvements were achieved in both the oral testosterone undecanoate and testosterone gel group and occurred in physical functioning, physical and emotional role limitation, social functioning, and bodily pain.

Changes in body composition parameters were also investigated in the 12-month study. The results for the oral testosterone undecanoate group showed spine bone mineral density, hip bone mineral density, lean body mass, and fat mass all improved significantly from baseline at 6 months with further improvements achieved at month 12.

Both the oral testosterone undecanoate and topical testosterone treatments were associated with minimal increases in serum prostate-specific antigen. Overall, the oral and topical treatments were associated with an increase of hematocrit in approximately 5% to 6% of patients.

“Importantly, there were no clinical events associated with the hematocrit increases in the oral testosterone undecanoate or the testosterone gel group, nor did any patient discontinue treatment because of elevated hematocrit,” Honig said.

Changes in blood pressure were followed using ambulatory monitoring. Among men treated with oral testosterone undecanoate, mean changes in 24-hour systolic and diastolic blood pressure were approximately 5 mm Hg and 2.5 mm Hg, respectively. Comparisons between men with and without hypertension at baseline showed that the average change was slightly higher in the hypertensive group.

Honig said, “It is unclear whether the blood pressure rise is just for oral testosterone undecanoate or a general class effect, as it has been seen with subcutaneous testosterone preparations as well. Most importantly, both oral testosterone undecanoate and topical gel groups showed no significant changes in liver enzyme measurements over a 12-month period.”

Honig is a consultant to Clarus Therapeutics and Endo.

Neither oral nor gel testosterones show significant effect on liver function test results.

QOL and body composition benefits seen with novel oral T treatment

A novel lymphatically delivered oral testosterone undecanoate (Tlando) is a fixed-dose, well-tolerated, and effective treatment for hypogonadism with liver health benefits that clearly differentiate it from the potentially hepatotoxic oral methyltestosterone, reported Irwin Goldstein, MD, at the American Urological Association 2020 Virtual Experience.

“This innovative product has exciting, paradigm-shifting potential for treating men with low testosterone,” said Goldstein, director of Sexual Medicine at Alvarado Hospital in San Diego, California, and clinical professor of surgery at the University of California San Diego.

“It offers the opportunity to provide safe, effective, and well-tolerated testosterone replacement through the oral route that is the generally preferred method for medication administration. In addition, available data indicate that it not only avoids the adverse hepatic effects that have historically limited use of oral testosterone, but it improves markers of nonalcoholic fatty liver disease [NAFLD] that is a serious and prevalent condition. Low testosterone (ie, hypogonadism) is common in males with NAFLD.”

Methyltestosterone is prone to cause liver toxicity with oral ingestion because it is directly transported to the liver through the portal vein, Goldstein said. In contrast, the lymphatically delivered oral testosterone undecanoate is a nonmethylated prodrug of endogenous testosterone, found in Tlando, that avoids first-pass metabolism in the liver and enters the systemic circulation via the lymphatics.

The safety and efficacy of Tlando for treating men with low testosterone was investigated in the 1-year SOAR trial that included 210 men who received the investigational product and a control group of 105 patients treated with topical testosterone gel.

Results from SOAR showed that the oral testosterone undecanoate was associated with a significantly greater increase in free testosterone levels compared with the topical product, and it improved key mental and sexual domains, reported Goldstein, who was an investigator in SOAR and an earlier dosing study.

Safety data in the study included measurement of liver enzymes and showed that reductions were consistently achieved in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and ɣ-glutamyl transferase among men who had elevated levels of those markers of liver injury at baseline. Rates of normalization for those 4 enzymes ranged from 31% for ɣ-glutamyl transferase to 67% for alkaline phosphatase.

Additional data on the liver effects of the novel testosterone undecanoate product were obtained in a smaller separate trial of men with hypogonadism. Using the objective Magnetic Resonance Imaging Proton Density Fat Fraction technique to measure liver fat percentage, it found that after 4 months, men with NAFLD at baseline achieved an approximately 40% reduction in liver fat. In addition, more than 75% of men who entered the study with NAFLD were considered “responders” to the oral testosterone undecanoate based on achieving a 30% or greater reduction in the percentage of liver fat.

In addition, the percentage of patients categorized as NAFLD-free rose during the study and nearly doubled by its conclusion, increasing from 34% at baseline to reach 63% at 16 weeks.

“Interestingly, the higher the baseline body mass index, the greater the reduction in liver fat achieved with Tlando treatment, and it appears that the improvement in liver fat does not appear to be explained by any decrease in body weight,” Goldstein said.

 Lipocine Inc provided funding for the study. Goldstein is on the consultant/advisory board of Lipocine Inc, does research for AbbVie Inc and Marius Pharmaceuticals LLC, is on the Clarus Therapeutics, Inc speakers’ bureau, and receives writing support from Endo International.

The treatment improves markers of nonalcoholic fatty liver disease, an investigator reports.

Author | Cheryl Guttman Krader, BS, Pharm

Articles

Patients undergoing post-URS stent placement more likely to visit ED

Photoselective vaporization of the prostate found safe, durably effective

QOL and body composition benefits seen with novel oral T treatment

Novel oral testosterone therapy shows liver health benefits