When to Proceed with Caution: Balancing Promise with Prudence in the Treatment of Urinary Incontinence

Abstract

The importance of identifying, evaluating, and disseminating safe and effective new therapies for stress urinary incontinence (SUI) cannot be overstated, and I commend Allan et al. for their study evaluating one such therapy.¹ They present interim (6 month) results of a 12-month feasibility study in which women with SUI were randomly allocated to receive one or two doses of cryogen-cooled monopolar radiofrequency (CMRF) intravaginally to evaluate treatment efficacy and safety. Similar proportions of women receiving one and two treatments experienced both subjective and objective improvements in SUI at 6 months post-treatment, and the only reported adverse event was a urinary tract infection. The authors conclude that CMRF vaginal treatment has a sustained benefit at 6 months and “merits a larger scale, randomized, blinded, and sham-controlled study to investigate this treatment for SUI.”¹

Anyone who provides care for women with SUI will undoubtedly agree wholeheartedly with this conclusion. The impact of SUI on women's quality of life and ability to remain physically active can be profound, and we acknowledge the limitations of existing surgical and nonsurgical treatments. We also understand the importance of a control group when evaluating the impact of a new therapy on incontinence symptoms, given that incontinence episode frequency decreases on average 33%, and as much as 57%, in women receiving placebo rather than active treatment.² Indeed, women with lower symptom severity, such as the women included in this trial, who had mild to moderate symptoms based on pad weights, have an increased placebo response in clinical trials for SUI.² We must thus interpret results of this feasibility trial with caution, given the lack of a control group and the knowledge that this patient population would be more likely to see an improvement in symptoms even with placebo.

Since this article was accepted for publication, Viveve, Inc. has announced results of the LIBERATE-International trial, a multicenter randomized double-blinded sham-controlled trial to evaluate the safety and efficacy of CMRF on SUI in women.³ Unfortunately, treated women and women who received a sham control in this large trial achieved similar reductions in 1-hour pad weights 6 months after treatment: median decrease from 12.8 g at baseline to 4.8 g in the treatment group and from 12.9 to 4.9 g in the sham control group.³ Although the feasibility results reported by Allan et al. appeared promising, we must acknowledge that the efficacy of CMRF therapy on SUI was no better than the efficacy of a sham control.

We must also learn from our history as a field. In our desire to offer women more durable and effective solutions for pelvic organ prolapse, we enthusiastically incorporated synthetic mesh augmentation at the time of surgical repair. With more robust studies of this technology, however, we realized that its benefits may not always outweigh its risks, leading the Food and Drug Administration (FDA) to classify vaginal mesh for anterior prolapse repair as class III, or “high risk,” in 2016.

The FDA issued a Safety Communication on July 30, 2018, the purpose of which was “to alert patients and health care providers that the use of energy-based devices … to treat symptoms related to menopause, urinary incontinence, or sexual function may be associated with serious adverse events. The safety and effectiveness of energy-based devices for treatment of these conditions has not been established.”⁴ The Safety Communication goes on to enumerate the potential serious adverse events that may result from application of energy-based therapies to the vagina, including “vaginal burns, scarring, pain during sexual intercourse, and recurring/chronic pain.” Although the fact that there were no serious adverse events in Allan et al.'s study is reassuring, we must also consider that early studies of vaginal mesh were similarly reassuring, and it is only with larger adequately powered studies that we can accurately assess risks of new therapies.

Coming full circle, the importance of identifying, evaluating, and disseminating safe and effective new therapies for SUI cannot be overstated. Allan et al.'s study provides helpful feasibility data that may inform future larger more rigorous trials of other CMRF therapy protocols for the treatment of SUI. Until those trials demonstrate benefits outweighing risks, we are obligated to proceed with caution.

References

Allan

, Bell

, Husarek

. Early feasibility study to evaluate the Viveve System for female stress urinary incontinence: Interim 6-month report. J Womens Health, 2020; 29:383–389.

Yalcin

, Bump

. The effect of previous treatment experience and incontinence severity on the placebo response of stress urinary incontinence. Am J Obstetr Gynecol, 2004; 191:194–197.

Press Release: Viveve Announces Top-line Results of LIBERATE-International Trial for SUI, Q2 Transition to New U.S. Commercial Model, and Pursuit of Financial and Strategic Alternatives. Englewood, CO, Accesswire, July 22, 2019. Available at: https://www.accesswire.com/552848/Viveve-Announces-Top-line-Results-of-LIBERATE-International-Trial-for-SUI-Q2-Transition-to-New-US-Commercial-Model-and-Pursuit-of-Financial-and-Strategic-Alternatives Accessed November 2, 2019 .

Food and Drug Administration. FDA warns against use of energy-based devices to perform vaginal “rejuvenation” or vaginal cosmetic procedures: FDA safety communication. 2018. Available at: https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-energy-based-devices-perform-vaginal-rejuvenation-or-vaginal-cosmetic Accessed November 2, 2019 .