Key takeaways from Sunday’s paradigm-shifting, practice-changing clinical trials in urology
These studies are expected to change the day-to-day practice of urology.
The new P2 program, paradigm-shifting, practice-changing clinical trials in urology, continued on Sunday with a head-to-head comparison of ureteroscopy (URS) and shockwave lithotripsy (SWL) for children with kidney stones. Results support important changes in AUA guidelines.
Current pediatric guidelines are based on weak evidence, said Gregory Tasian, MD, MSc, MSCE, Cheers for CHOP chair in clinical epidemiology of pediatric urological disease at Children’s Hospital of Philadelphia. And none consider outcomes reported by or prioritized by patients.
“Over 80% of children with kidney stones have ureteroscopy,” Dr. Tasian said, during the Sunday morning Plenary session. “And we didn’t know which is the best surgery for children with kidney stones.”
The Pediatric KIDney Stone (PKIDS) Care Improvement Network launched a prospective cohort study to compare the two approaches between April 2020 and October 2023 across 29 centers in the United States and Canada. A total of 1,070 patients received URS and 197 had SWL.
The primary outcome was stone clearance. Secondary outcomes focused on physical, social and emotional health by patient-reported outcomes measurement information system (PROMIS) and urinary measures.
There was no overall difference in stone clearance, Dr. Tasian reported, although SWL clearance rates declined with increasing stone size from 10 mm to 15 mm.
But patient-reported outcomes of physical, emotional and social health were significantly better with SWL. Patients reported worse urinary symptoms, more pain, and more pain interference for URS compared to SWL. Patients with SWL returned sooner than those with ureteroscopy.
“The PKIDS trial supports revision of the AUA guidelines,” Dr. Tasian said. “There should be a new size threshold of 15mm for kidney stones, guidelines should recommend shockwave lithotripsy, and we should consider greater stone clearance and worse patient experience with ureteroscopy for kidney stones 10mm to 15mm.”
COCKTAIL inconclusive
David A. Velasquez
“The most common cause of ED is urethro-genital,” said David A. Velasquez, andrology research fellow at the University of Miami Desai Sethi Urology Institute and fourth-year medical student at The University of Chicago Pritzker School of Medicine, “but most ED treatments do not target the physiology.”
COCKTAIL enrolled 56 men 30 to 80 years old with mild to moderate ED to either SWT + PRP or sham shockwave + saline injections. Primary endpoints were safety and serious adverse events of treatment. Secondary endpoints included efficacy, change in international index of erectile function (IIEF) score at three and six months from baseline and percentage of participants who achieved minimally clinically important differences in IIEF.
“We didn’t see any adverse events,” Velasquez reported, “and we didn’t see any statistically significant differences in mean IIEF scores between the two groups, suggesting a significant placebo effect. We need further investigations with larger cohorts to explore the potential efficacy of combined PRP/SWT on the underlying causes of ED.”
Office-based removal of small stones safe, effective
Two clinical trials with two new technologies, ultrasonic propulsion and burst wave lithotripsy (BWL), should move urologists to consider treating small stones in the office.
“We tend to observe small stones and discuss treatment only if they get larger,” said Mathew Sorensen, MD, MS, FACS, associate professor of urology at the University of Washington and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound Veterans Administration. “Our current management is to try to avoid surgery. But we are not trying to avoid ED visits or painful events for our patients.”
A randomized controlled trial of 84 patients with residual fragments after ureteroscopy or shockwave lithotripsy compared propulsion to control, with observation for five years. Outcomes included surgery; symptomatic, unscheduled ED visits; stone growth; fragment passage within 21 days; and adverse events within 90 days. Outcomes were assessed by CT at 90 days and annually for up to five years.
The propulsion group had 70% lower risk of relapse at five years and 52% longer time to relapse, Dr. Sorenson said, and no medications were needed during any of the procedures.
BWL is focused ultrasonic lithotripsy to fracture stones using real-time ultrasonic guidance to treat small stones in the kidney and ureter that might currently be observed. Patients can be treated in the office without anesthesia.
“We can shift our goal to preventing ED visits, painful symptomatic events and offer earlier intervention for symptomatic ureteral stones,” Dr. Sorenson said.
Preliminary results for BWL in small stones showed 30% of patients stone-free at 90 days, a mean reduction in stone volume of 86% and median reduction of 100% with mild, self-limiting adverse events.
Results for renal and ureteral stones headed to surgery showed 86% of patients required no sedation with 58% stone-free, 72% stone-free or <4 mm fragments and 92% fragmentation.
“We showed that removing small stones and residual fragments reduces relapse, and that practice may change to treat stones in the office or in the ED,” Dr. Sorenson said. “Our paradigm may shift to treat small renal stones we currently observe.”
COURAGE backs selective β3-adrenergic receptor agonist for BPH
New data support the use of Vibegron, a selective β3-adrenergic receptor agonist, for BPH. The drug is currently approved by the Food and Drug Administration to treat overactive bladder (OAB), a common complication of BPH.
The COURAGE trial randomized 1,080 men with BPH and persistent OAB symptoms to daily Vibegron (538) or placebo (542). The co-primary endpoints were change from baseline (CFB) in mean daily micturition and urgency episodes at a week. Secondary CFB were mean nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score (IPSS) storage score, and volume voided per micturition.
“All of our variables improved,” reported David Staskin, MD, Tufts University School of Medicine. “Vibegron was associated with significant reductions in daily micturition and urgency episodes as well as our secondary endpoints. Symptoms really did improve compared to placebo as early as week two.”
IMPACT supports PUL over medication for LUTS/BPH
The 2023 amendment to the AUA guidelines for BPH included prostatic urethral life (PUL) as a treatment to consider but did not recommend the procedure. The interim data from the IMPACT head-to-head comparison of PUL versus tamsulosin show PUL is superior to medication with largely mild to moderate adverse events in men with lower urinary symptoms (LUTS)/BPH.
“IMPACT is the largest head-to-head RCTD comparing efficacy, safety and patient experience after a minimally invasive surgery for LUTS/BPH and medical therapy,” said Claus Roehrborn, MD, UT Southwestern Medical Center. “PUL has better symptom relief and quality of life improvements, higher patient satisfaction and goal attainment and more improvements in daily activities.”
The trial randomized 235 men with LUTS/BPH to PUL (105) or tamsulosin (129) with follow-up at three, six and 12 months. The primary endpoint was change in BPH symptoms at three months by IPSS score. Secondary endpoints included quality of life measures, satisfaction with treatment, achievement of treatment goal and adverse events.
PUL patients IPSS total score improvement of 10 at three months versus 3.1 for medication. Quality of life scores improved by 2.2 for PUL patients versus 0.5 for medication. PUL also showed higher scores for satisfaction of treatment and achievement of treatment goals.
More than half of PUL patients (55.6%) had at least one adverse event. Most were mild/moderate and resolved within two weeks. Medication AEs were fewer (17.8%) and persisted longer.
Dr. Roehrborn said subsequent reports will include outcomes to one year and crossover rates.
Hydrodistention
Interstitial cystitis/bladder pain syndrome (IC/BPS) accounts for 8% of all outpatient urology visits in the U.S. and is often treated using cystoscopy with hydrodistention. Treatment practices vary widely in terms of hydrodistention pressure, duration and number of distentions.
“We were surprised to find there were no randomized controlled trials of hydrodistention, and AUA guidelines are broad,” said Alex Zhu, fourth-year resident at the University of Michigan. “The key question is, what is the optimal technique for hydrodistention?”
A prospective trial randomized 104 patients with IC/BPS to hydrodistention at 30 or 80 cm, lasting one or two minutes, and performed once or twice. The primary endpoint was the difference in IC Symptom Index score at four weeks. Secondary endpoints included IC Symptom Index at one and 12 weeks, overall urinary symptoms, percent moderately/markedly improved and adverse events.
There were no differences between the two groups for hydrodistention pressure or duration, Zhu reported, but patients with two distentions had lower IC Symptom Index scores versus one distention. Patients with two distentions also reported greater reduction in overall urinary symptoms and the two-distention group had a greater percentage of responders.
There were no episodes of sepsis, urinary retention or bladder rupture and no significant difference in urinary tract infections or readmissions by hydrodistention technique.
“We know that hydrodistention leads to clinically meaningful improvement in 40% of patients at one month,” Zhu said. “A higher number of distentions may lead to a more durable response. Urologists should consider performing hydrodistention at low pressure, 30 cm and short duration, one minute, which reduces risks of bladder injury operative times and anesthetic exposure.”
