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

Cheryl Guttman Krader, BS, Pharm

Results from 2 years of follow-up in a prospective clinical trial demonstrate that sacral neuromodulation (SNM) using a rechargeable device (Axonics) provides durably safe, effective treatment for urinary urgency incontinence (UUI), according to the latest report from investigators in the ARTISAN-SNM trial (NCT03327948).

“The 2-year results are very impressive and underline what SNM can offer to patients with UUI. The clinical outcomes, along with the high rate of patient satisfaction, are testament to the effort the manufacturer invested into developing this technology,” said Andrea M. Pezzella, MD. “The rechargeable device has really raised the bar in the SNM treatment space. I am confident that the results of the study will raise awareness and encourage more physicians to adopt this therapy for long-term management of patients with UUI.”

Pezzella is medical director of Southern Urogynecology in West Columbia, South Carolina, and lead author of the published paper summarizing the 2-year outcomes of the ARTISAN-SNM trial. Patients were enrolled if they had 4 or more UUI episodes in a 3-day diary, including 1 or more episodes per day. A total of 129 patients (98% female) aged 21 to 86 years underwent device implantation in a single, nonstaged procedure.

Among 121 patients who completed the 2-year follow-up visit, 93% were judged to be “therapeutic responders” based on achieving a 50% or greater reduction in UUI episodes in a 3-day period. Eighty-two percent of the responders achieved at least a 75% reduction from baseline in UUI episodes, and 37% were dry (100% reduction). Mean number of UUI episodes per day fell from 5.6 at baseline to 1.0 at 2 years. There were no correlations between patient responses and either frequency of daily UUI episodes or time since diagnosis. “Particularly striking is that the responder rate was 88% in the rigorous as-treated analysis that included all study participants and classified anyone who had undergone explantation or exited the study for any reason as treatment failures,” Pezzella told 

Health-related quality of life was evaluated using the validated International Consultation on Incontinence Modular Questionnaire Overactive Bladder Quality of Life questionnaire and showed an improvement from baseline that was both highly statistically significant and clinically meaningful. Statistically significant improvements were also achieved in all subscale scores.

Responses on patient satisfaction questionnaires showed that at 2 years, 94% of participants were satisfied with the therapy and 93% said they would undergo the therapy again with the same expected results. Questions on device recharging showed 91% of participants considered it easy and 94% rated the frequency and duration as acceptable. Almost all participants (98%) reported recharging the device no more than once a week, and the duration of recharging was less than 1 hour for 88% of participants. These measures were stable throughout the 2-year follow-up.

“The patient satisfaction data should dispel any concern that patients would consider the need for recharging the device difficult, inconvenient, or bothersome, and an age-based analysis showed no differences comparing participants who were older than 65 years with their younger counterparts,” Pezzella said. “Recharging electronic devices is a fact of modern living, and with its short and infrequent charging sessions, the rechargeable SNM unit is very user-friendly.”

There were no serious procedure- or device-related adverse events (AEs). The most common device-related AE was uncomfortable change in sensation or magnitude of stimulation (9%), which was resolved through remote adjustments to the system. “The take-home message is that the rechargeable SNM has a very favorable safety profile, and the high rate of success has been, at least for me, a game changer in SNM that proves to be an invaluable treatment option for our patients,” Pezzella said.

Formal follow-up of patients enrolled in the ARTISAN-SNM trial has been completed. The manufacturer has established a postmarketing patient registry and will use the data collected to evaluate the real-world safety and efficacy of the rechargeable SNM system.

1. Pezzella A, McCrery R, Lane F, et al. Two‐year outcomes of the ARTISAN‐SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system. 

2021;40(2):714-721. doi:10.1002/nau.24615

Articles

“The 2-year results are very impressive and underline what SNM can offer to patients with UUI," said Andrea M. Pezzella, MD.

 Efficacy, safety of rechargeable SNM device for OAB sustained at 2 years

Treatment for high-risk non–muscle-invasive bladder cancer (NMIBC) with hyperthermic intravesical chemotherapy (HIVEC) using high-dose mitomycin-C (MMC) is safe, well tolerated, and appears efficacious after short-term follow-up, according to a report from Duke University urologists.

 In a paper presenting the first North American clinical experience with this modality, the investigators summarized outcomes from a cohort of 14 patients who received MMC HIVEC because of the BCG shortage. The median number of instillations received was 6, and the median follow-up for the series was 11 months.

The MMC HIVEC was well tolerated by 11 (79%) patients. Seven patients (50%) developed adverse events (AEs), but all were grade 1 or 2. During the available follow-up, 2 patients (14%) experienced a cancer recurrence, but both had discontinued MMC HIVEC after only 2 treatments.

Scott P. Campbell, MD, third-year urology resident at Duke University Medical Center, Durham, North Carolina, told 

, “Given the limited supply of BCG and the lack of reliable treatments in the post-BCG setting, our biggest priority is to continue to identify therapies for bladder cancer that are safe and effective alternatives to BCG. Our study demonstrates the feasibility of HIVEC MMC and suggests it is a reasonable substitute for BCG during global shortages. We hope that clinical trials stem from this series to help the urologic oncology community better understand how to optimize HIVEC, including testing alternative agents to MMC.”

The 14 patients included in the MMC HIVEC series comprised 4 with intermediate-risk disease and 10 with high-risk NIMBC. Twelve patients had recurrent tumors of which 11 had been previously treated with intravesical BCG (median, 6 treatments). Three patients were BCG-naïve.

The MMC HIVEC was administered at a concentration of 2 mg/mL (120 mg diluted in 60 mL sterile water) using a convective hyperthermia system (Combat BRS) with an induction course of 6 weekly instillations followed by up to 12 additional monthly treatments in the setting of a negative postinduction cystoscopy. Dwell time was 60 minutes heated and 30 to 60 minutes unheated following catheter removal.

MMC was chosen because it had been used in nearly all clinical trials investigating hyperthermia as an adjunct to intravesical chemotherapy, said first author Dominic C. Grimberg, MD, urology resident at Duke University Medical Center. “MMC has the best track record as an alternative to BCG, and although in prior studies of hyperthermic chemotherapy, MMC was administered at a concentration less than or equal to 1 mg/mL, we used the higher dose that is the accepted standard concentration in the United States based on a phase 3 trial,” he said.2

Grimberg added, “There are multiple hyperthermia systems, but the convective system we chose is small, reliable, low maintenance, widely available, affordable, and easy to use. Therefore, it could be rapidly implemented into clinical practice in our cancer center.”

AEs occurred during the instillation in 3 patients (bladder spasms in all and hematuria in 1) and led 2 patients to discontinue treatment. Four patients developed a pruritic rash thought to be MMC allergy as a delayed AE, and another developed leukopenia that resolved after the treatment was stopped. The investigators postulated that the higher-than-expected rate of systemic AEs reflected increased drug delivery using hyperthermia. Patient follow-up is continuing, and the investigators plan to report on longer-term outcomes over the next several months.

Brant A. Inman, MD, MS, Cary N. Robertson, MD, Associate Professor of Urologic Oncology at Duke University School of Medicine, is senior author of the paper. He told 

, “Many patients have already been seen at a 12-month visit, and preliminarily the data show that durable oncologic control is possible when patients are able to receive full induction courses of high-dose HIVEC MMC.”

1. Grimberg DC, Dudinec J, Shah A, Inman BA. Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non–muscle invasive bladder cancer during BCG shortage. 

Published online January 20, 2021. doi:10.1016/j.urolonc.2020.12.025

2. Au JL, Badalament RA, Wientjes MG, et al; International Mitomycin C Consortium. Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial. 

. 2001;93(8):597-604. doi:10.1093/jnci/93.8.597

"Our study demonstrates the feasibility of HIVEC MMC and suggests it is a reasonable substitute for BCG during global shortages," says urologist Scott P. Campbell, MD.

Intravesical hyperthermia with high-dose mitomycin-C shows promise as BCG alternative for NMIBC

The FDA has approved the third-generation version of Axonics Modulation Technologies rechargeable implantable neurostimulator (INS) for the treatment of patients with urinary and bladder dysfunction.

The INS device was launched commercially in the United States in November 2019. A second-generation version approved in April 2020 prolonged the device’s recharge interval. The third-generation model upgrades the software embedded in the device and enhances the functionality of the remote control, which is used by patients to monitor their stimulation level and the need to recharge the stimulator.

“This is another significant upgrade we have made to the Axonics System, underscoring our commitment to continuous innovation that enhances the patient experience. While our long-lived INS device is as close to a 'set it and forget it' therapy, the new features will benefit physician practices in which patients have to travel long distances should they require therapy adjustments. We are confident that continuing to ensure excellent patient experiences will drive significant market expansion in the years ahead and result in SNM therapy becoming the preferred solution for urinary and bowel dysfunction,” Raymond W. Cohen, CEO of Axonics, stated in a press release.

Efficacy data for the Axonics rechargeable sacral neuromodulation (SNM) system were presented during the 2020 American Urological Association Virtual Experience.

 The results were 1-year follow-up data from the pivotal trial that led to the initial approval of the device. The findings showed that SNM with the Axonics INS provided highly safe and durably effective treatment for urinary urgency incontinence (UUI).

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. It was also noted that patients had clinically significant improvements in quality of life (QoL) and a high level of satisfaction with the device.

The single-arm trial 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.

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. All of the QoL improvements were statistically significant and far exceeded the minimum 10-point change that is considered clinically significant.

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%).

1. Axonics® Receives FDA Approval for Third-Generation Implantable Neurostimulator. Published online February 16, 2021. Accessed February 22, 2021. https://bit.ly/3uhPIyJ.

2. 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.

The rechargeable implantable neurostimulator is approved for the treatment of patients with urinary and bladder dysfunction.

FDA approves updated version of SNM device for OAB

Analyses of data collected in a prospectively maintained database support the recommendation for urologists to consider “MIP,” the minimally invasive version of mini-percutaneous nephrolithotomy (mini-PCNL), for stone removal in patients with medium-sized stones (10-20 mm), say investigators from the University of California, San Diego.

Investigators reported their initial experience with MIP in a paper published online in the 

 The study included data for 46 patients who underwent the procedure during a period from 2017 to 2019 and had reviewable CT imaging postoperatively. Initial stone size averaged 21.32 mm, measured between 1.9 and 20 mm in 29 patients (63%), and ranged up to 84 mm.

Based on postoperative CT imaging reviewable for 46 patients, 20 patients (43%) were stone-free, defined as having no identifiable fragments seen. Another 5 patients (11%) had residual fragments 0 to 2 mm, 3 patients (7%) had residual fragments 2 to 4 mm, and 18 patients (39%) had residual fragments larger than 4 mm. The stone-free rate for patients with initial stone burdens of less than or equal to 0 mm and greater than 10 to less than or equal to 20 mm was 57% and 52%, respectively, and dropped to 25% for patients with larger stones.

“The MIP procedure, which is performed using a proprietary nephroscope that uses irrigation to remove stones [Karl Storz MIP-M access sheath], has been widely used in Europe but only recently introduced in North America,” said Roger L. Sur, MD, professor of urology, University of California San Diego. “This is the first single-institution analysis of MIP cases in North America. Based on the use of a strict definition to define stone-free status, which is the main strength of our study, the outcomes achieved with MIP are comparable to the results of both retrograde intrarenal surgery and standard PCNL. Now, further studies assessing its outcomes are needed to determine the exact role of MIP in renal stone disease,” he added.

Sur and coauthor Seth Bechis, MD, performed all of the MIP procedures. The study population included equal numbers of men and women. The patients had a mean age of 60 years.

Other outcomes analyses showed that the mean operating room time was 118 minutes. The majority of patients (n=28, 61%) were discharged on the day of surgery (within 1-2 hours after the procedure), and 16 patients (35%) went home the next day. Eight patients (17%) were readmitted. Three-fourths of the complications were classified as Clavien I or II, and none were higher than Clavien III. Only 1 patient (2%) had an unplanned return to the operating room.

Sur noted that there has been an ongoing debate about the utility of mini-PCNL with respect to whether or not any differences associated with the procedure are clinically significant.

“For example, reported outcomes with mini-PCNL suggest that it decreases blood loss compared to standard PCNL, but the question of whether the difference is meaningful to patients remains unanswered,” he said. “Our observational study does not provide a direct comparison to another modality with control for key variables that can influence outcomes. Furthermore, because most patients were discharged on the day of surgery, it lacks assessment of commonly reported postoperative hematologic changes.”

These limitations are being addressed in a study undertaken by the Endourology Disease Group for Excellence Consortium. The study is a randomized controlled trial with 6 participating centers that is comparing MIP with standard PCNL and is designed to determine if the minimally invasive procedure is superior to PCNL for minimizing operative blood loss.

and Seth Bechis, MD, are consultants for Karl Storz.

1. Holst DD, Bechis SK, Zupkas P, et al. Minimally invasive percutaneous nephrolithotomy: initial North American experience. 

Published online November 16, 2020. doi:10.1089/end.2020.0574

Analyses of data collected in a prospectively maintained database support the recommendation for urologists to consider the minimally invasive version of mini-percutaneous nephrolithotomy for stone removal in patients with medium-sized stones (10-20 mm).

Cheryl Guttman Krader, BS, Pharm

Articles

Efficacy, safety of rechargeable SNM device for OAB sustained at 2 years

Intravesical hyperthermia with high-dose mitomycin-C shows promise as BCG alternative for NMIBC

FDA approves updated version of SNM device for OAB

Observational study results put minimally invasive PCNL in a favorable light