Cheryl Guttman Krader, BS, Pharm

Results from 1 year of follow-up of patients enrolled in a pivotal clinical trial show that sacral neuromodulation (SNM) with a miniaturized, implanted rechargeable device (Axonics System) provides highly safe and durably effective treatment for urinary urgency incontinence (UUI), said Howard B. Goldman, MD, at the 2020 American Urological Association Virtual Experience1.

Goldman, a professor of urology at Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio, presented the research on behalf of the study investigators. He reported that reduction in UUI episodes observed at the study’s primary end point at 6 months were sustained through 1 year, and the safety profile of SNM with the rechargeable device was consistent with SNM experience reported in the literature.

“Patients also benefited with clinically significant improvements in quality of life, had a high level of satisfaction, and found the charging task user friendly,” Goldman said.

The rechargeable SNM system received FDA approval for treating UUI, urinary urge frequency, and urinary retention in November 2019. The pivotal trial supporting the decision had a single-arm design and enrolled 129 patients at 19 centers in the United States and western Europe. Subjects were eligible for inclusion if they had 4 or more UUI episodes in a 3-day diary, including 1 or more episode per day. Individuals with more than a minimal level of stress incontinence, anatomic urinary tract obstruction, or an underlying neurological condition were excluded.

The trial’s participants ranged in age from 21 to 86 years (mean 59) and were almost entirely women (98%). Mean UUI episodes per day at baseline was 5.6.

The primary end point for the study assessed the rate of therapy responders at 6 months. Ninety percent of women, defined as participants achieving a 50% or greater reduction in UUI episodes per 3 days, achieved the end point. The therapy responder rate was 89% at 1 year.

“The reduction in UUI episodes was quite significant in the study cohort,” Goldman said.

“At 6 months it had decreased to 1.3 episodes per day and it was 1.4 at 1 year. Furthermore, more than three-fourths of patients had at least a 75% reduction in daily UUI episodes at 1 year, and the remaining participants achieved at least a 50% reduction.”

Quality of life was evaluated using a validated questionnaire (International Consultation on Incontinence Questionnaire Overactive Bladder Quality of Life Module). At 1 year, changes from baseline in the total score and in scores for individual domains (concern, coping, sleep, and social) ranged from 22 to 34.

Quality of life improvements statistically significant

“All of the improvements were statistically significant and far exceeded the minimum 10-point change that is considered clinically significant,” Goldman said.

At 1 year, 93% of patients said they were satisfied with the therapy, and 92% said they would undergo the therapy again with the same expected results. Questions pertaining to the charging of the device showed that it was considered easy by 89% of participants, and 96% rated the frequency and duration of charging as acceptable. Ninety-five percent of participants reported recharging the device no more than once a week, and 86% reported that the total charge time was 60 minutes or less.

There were few adverse events (AEs) in the series and no serious device-related AEs. The most common AE was uncomfortable change in sensation or magnitude of stimulation (5%).

No patient underwent surgical intervention for pain, but 3 patients underwent a revision and the device was explanted in 1 patient due to infection.

“Interestingly, 6 patients had magnetic resonance imaging during the year after implantation, which was full body in 4 participants, without any evidence of adverse events,” Goldman said.

The rechargeable SNM device is also approved for the treatment of fecal incontinence, and changes in fecal incontinence were evaluated prospectively in the pivotal trial. Data collected in the subgroup of patients who had fecal incontinence at baseline showed they experienced a statistically significant improvement at 6 months and even greater benefit at 1 year.

“Overall, 91% of patients who had bowel symptoms at study entry were satisfied with how that problem was helped as well,” Goldman said.

Disclosures: Dr Goldman is a study investigator and a consultant to Axonics Modulation Technologies. Axonics Modulation Technologies provided funding for the study.

1. Long Term Clinical Results on Treatment of Urinary Urgency Incontinence with the Axonics Rechargeable Sacral Neuromodulation System. Presented at: 2020 AUA Virtual Experience. Abstract PD27-12.

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The reduction in urinary urgency incontinence episodes observed was “quite significant,” an investigator said.

Rechargeable neuromodulation system safe and efficacious through 1 year

Transcriptome profiling of tumor specimens collected from patients with biochemically recurrent prostate cancer participating in a phase 3 clinical trial further validates the performance of a commercially available genomic classifier (Decipher) for predicting the risk of distant metastasis.

In addition, the findings indicate that the genomic classifier has value for guiding the selection of patients undergoing salvage radiotherapy for recurrence who are most likely to benefit from treatment intensification with anti-androgen therapy, said Felix Y. Feng, MD.

The study authors analyzed data from NRG/RTOG 9601, a randomized, placebo-controlled phase 3 trial investigating the addition of bicalutamide to salvage radiotherapy. Feng, a professor of radiation oncology, urology, and medicine, director of the Benioff Initiative for Prostate Cancer Research, and vice chair for translational research, department of radiation oncology at the University of California, San Francisco, presented the research at the 2020 Genitourinary Cancers Symposium.

, “Our study is the first to investigate the performance of a clinical-grade genomic classifier in the context of a prospective, randomized post-prostatectomy trial, and the findings provide the strongest validation to date of its prognostic value.”

However, another main aim of the current analysis was to see whether the commercially available 22-gene biomarker panel could help guide decisions on implementing hormone therapy.

“Although NRG/RTOG 9601 showed a statistically significant survival benefit for men treated with bicalutamide compared to placebo-treated controls, only a minority of patients who received anti-androgen therapy benefited from this treatment,” Feng explained. “Therefore, the study’s result should not be interpreted to mean that hormone therapy be given to all men with PSA recurrences after prostatectomy.

“Our present analysis indicates that the genomic classifier can be a useful adjunct for clinical decision-making. In that regard, our study makes an important contribution to patient care as the management of prostate cancer moves toward treatment personalization.”

NRG/RTOG 9601 randomized 760 men receiving salvage radiotherapy to treatment with placebo or bicalutamide for 2 years. Patients were eligible for the study if they had pT3 or pT2 disease with a positive margin, no nodal involvement, and a prostate-specific antigen (PSA) of 0.2 to 4.0 ng/mL.

The study investigating the genomic classifier used formalin-fixed, paraffin-embedded prostatectomy specimens. Tissue from 352 of the study’s participants, representing equal numbers of men from the placebo and bicalutamide groups, were included in the analysis and demonstrated to be representative of the overall population.

The performance of the genomic classifier as an outcomes predictor was analyzed considering its generated score (0-1) as a continuous variable. In multivariable analyses adjusting for age, race, Gleason score, T-stage, margin status, entry PSA, and treatment arm, the genomic classifier was a statistically significant, independent predictor of distant metastases, prostate cancer-specific mortality, and overall survival (OS).

Hormone therapy benefit smaller in low-risk group

To analyze its potential benefit for identifying patients likely to benefit from hormone therapy, men were first divided into two groups based on their genomic classifier risk stratification: low risk (n = 183) vs intermediate or high risk (n = 169). The results showed that the benefit from hormone therapy was consistently smaller in the low-risk group vs the intermediate- or high-risk group, whether considering 12-year risk of distant metastases, 12-year risk of prostate cancer-specific mortality, or 12-year OS.

Findings from additional analyses that included only men who received early salvage radiotherapy when the PSA was less than 0.7 ng/mL (n = 175) showed that in this particular subgroup, men categorized as low risk according to the genomic classifier appeared to derive no benefit from hormone therapy when considering any of the three outcomes.

“Although the results were not statistically significant, the data showed that the 12-year overall survival was numerically worse for men in the low-risk group if they received hormone therapy than if they were treated with placebo. This suggests that, if we give hormone therapy to all patients with PSA recurrences after surgery, we may be overtreating those with low Decipher scores and low PSAs at the time of initiation of radiation therapy,” Feng said.

Disclosures: Dr. Feng has consulted for Astellas, Bayer, Blue Earth Diagnostics, Celgene, Clovis Oncology, Janssen, Roivant Sciences, and Sanofi. For full disclosures, see

The classifier can be a useful adjunct for clinical decision-making, an investigator says.

Research confirms prognostic performance of genomic classifier

	Analyses of data from 5 years of prospective follow-up in the pivotal trial supporting regulatory approval of the prostatic urethral lift ([PUL] UroLift System, NeoTract) show that the minimally invasive procedure remains safe and provides rapid and durable benefits for men with symptomatic BPH.

	That finding was reported by Claus G. Roehrborn, MD, at the European Association of Urology annual congress in London.

Dr. Roehrborn“This is the largest and longest study of PUL, and it is a very high-quality trial that has FDA oversight and independent reviewers assessing the efficacy and safety data. In addition, it had a 5-year retention rate of 74%, which is considerably higher than many prior pivotal studies of minimally invasive surgical therapies for BPH,” said Dr. Roehrborn, professor and chair of urology at the University of Texas Southwestern Medical Center, Dallas.

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	“The study results show that PUL delivers a truly minimally invasive patient experience that avoids serious side effects of traditional surgery and is the only procedure for BPH that does not cause sustained sexual dysfunction. Furthermore, the data show that symptom relief and quality of life improvement occur rapidly after PUL, and men can expect that the significant benefits they experience at 1 month will persist for 5 years.

	“Given the safety and benefits of PUL and considering the large number of patients for whom pharmaceutical therapy is either insufficient or intolerable due to side effects, cost, or inconvenience, I believe that PUL should be considered an early treatment option for symptomatic BPH.”

	LIFT, the pivotal trial of PUL, was a multinational study that randomized 206 men 2:1 to undergo PUL or a sham procedure. Eligible men were aged ≥50 years with an International Prostate Symptom Score (IPSS) ≥13, peak flow rate (Qmax) ≤12 mL/s, and prostate volume 30 cc to 80 cc. Of the 140 men randomized to PUL, 137 were evaluated at 1 month and 104 were available at 5 years.

Next: Retreatment rate 13.6% in PUL group

	Compared with baseline, mean IPSS and mean IPSS quality of life scores in the PUL arm improved by 44% and 42%, respectively, at 1 month 

<.001 for both) and by 36% and 50%, respectively, at 5 years 

<.001). Qmax was improved by 3.5 mL/s at 5 years (+44% vs. baseline).

	Further underscoring the durability of improvement provided by PUL were data on the surgical retreatment rate, which was only 13.6% (2% to 3% per year) in the PUL group.

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	“Looking at the data in other ways, 86% of men did not require another procedure for BPH, and the retreatment rate also compares very favorably with other procedures for BPH,” said Dr. Roehrborn. “For thermally based procedures, the 5-year retreatment rate ranges from 20% to 50%, and the annual retreatment rate for TURP is 1% to 2%.”

	Dr. Roehrborn also highlighted the minimally invasive nature of the PUL procedure. In LIFT, 99% of the PUL procedures were done under local anesthesia, 68% of men avoided postprocedural catheterization, and men returned to normal activities at an average of 8.6 days. In a follow-on study of men crossed over from the sham arm to PUL, all procedures were done under local anesthesia, 80% of men avoided catheterization, and the average time to return to normal activities was 5.1 days.

	“PUL is truly a minimally invasive procedure that can be offered in the office setting, and those features also make it a unique and important treatment option,” Dr. Roehrborn said.

	Dr. Roehrborn is an investigator for NeoTract, NxThera, and Procept.

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Analyses of data from 5 years of prospective follow-up in the pivotal trial supporting regulatory approval of the prostatic urethral lift ([PUL] UroLift System, NeoTract) show that the minimally invasive procedure remains safe and provides rapid and durable benefits for men with symptomatic BPH.

Urethral lift: 5-year data point to procedure’s durability

Patients undergoing ureteroscopy while remaining on anticoagulant therapy may be at increased risk for bleeding complications, including significant bleeding events and unplanned returns to the operating room, according to a retrospective study from Mayo Clinic, Rochester, MN.

Use new data to inform unique patient group

The authors were prompted to analyze the safety of continuing anticoagulation when performing ureteroscopy because anecdotally, their experience seemed to conflict with the published recommendation from the AUA/International Consultation on Urological Diseases (AUA/ICUD) stating that “Ureteroscopy can be performed with continuing oral anticoagulation and antiplatelet therapy” 

 They presented their findings at the 2016 World Congress of Endourology in Cape Town, South Africa.

“The AUA/IUCD statement is based on a systematic review of the literature that identified only three small retrospective series that reported no increase in bleeding-related complications in patients on anticoagulation or antiplatelet therapy undergoing utereroscopy. We thought the evidence, however, was insufficient to support such a conclusive statement,” said presenting author JÃ³hann P. Ingimarsson, MD.

“Further studies are needed to validate our findings, and we are not advocating against stopping anticoagulation in all patients undergoing ureteroscopy. Rather, the decision should be individualized taking into account the risks associated with procedural-related bleeding versus a thromboembolic event. However, we believe our study provides information that should be used for preoperative planning and patient counseling while also underscoring the need for practice recommendations to be evidence-based.”

Dr. Ingimarsson was involved in the study when he was a minimally invasive urologic surgery fellow at Mayo Clinic. He is currently attending surgeon, Maine Medical Center, South Portland.

To investigate the risk of bleeding complications when patients undergoing ureteroscopy continued on anticoagulation, the authors undertook a chart review covering the period from June 2009 to February 2016. They identified 4,799 ureteroscopic procedures, of which 528 involved patients on anticoagulation within 90 days prior to the procedure. After excluding patients on concomitant antiplatelet therapy, whose anticoagulant therapy could not be verified, and those who had another surgery concomitant with ureteroscopy, 272 patients remained in the study population.

Overall, the patients had a mean age of 70 years. The surgical technique included both semirigid and flexible ureteroscopy procedures and routine stent placement.

Bleeding-related complication rates were analyzed with the 272 patients divided into three groups according to whether the anticoagulation was continued (n=26), bridged with enoxaparin (n=53), or held (n=193). The patients who continued on anticoagulation were further stratified by whether they were on warfarin (n=17) or a non-vitamin K antagonist (n=9).

Overall, 5.9% of patients had a significant bleeding-related event, which included emergency department visits for hematuria, re-admission for hematuria management, or return to the operating room for ongoing bleeding. Compared with the rate in the group that held anticoagulation, the rate of a significant bleeding-related event was about fivefold higher in the group that continued anticoagulation and about threefold higher in the bridged group (15% and 9% vs. 3%; 

Among the patients who continued anticoagulation, rates of all bleeding-related complication endpoints were higher in the subgroup on non-vitamin K antagonists compared with those on warfarin, although none of the differences achieved statistical significance.

“Our study may have been underpowered to detect statistically significant differences for these comparisons, but the higher rate of bleeding-related complications among patients on non-vitamin K antagonists is noteworthy considering these agents are being increasingly prescribed for anticoagulation compared with warfarin,” Dr. Ingimarsson said.

There were some significant differences between the three study groups in their baseline and operative characteristics. Patients on bridged anticoagulation had the highest mean Charlson Comorbidity Index and mean ASA score, and no patients who continued anticoagulation had ureteral dilation performed. In addition, some baseline and operative characteristics were associated with a significantly higher rate of various bleeding outcomes. Due to the small number of events overall, however, it was not possible to conduct a multivariate analysis to control for potential confounders and determine whether continuing anticoagulation or any of the other factors independently predicted bleeding risk.

“However, the group that continued on anticoagulation was very similar compared with the held anticoagulation group other than for the fact that ureteral dilation was not performed in any patients continuing on anticoagulation. We expect surgeons chose not to perform ureteral dilation in the patients continuing on anticoagulation as a matter of caution, and that probably limited the bleeding complication rate,” Dr. Ingimarsson told 

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Patients undergoing ureteroscopy while remaining on anticoagulant therapy may be at increased risk for bleeding complications, including significant bleeding events and unplanned returns to the operating room, according to a retrospective study

Author | Cheryl Guttman Krader, BS, Pharm

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Rechargeable neuromodulation system safe and efficacious through 1 year

Research confirms prognostic performance of genomic classifier

Urethral lift: 5-year data point to procedure’s durability

Anticoagulant use in URS patients ups bleeding risk