To evaluate efficacy and safety of the FotonaSmooth® device in the treatment of stress urinary incontinence (SUI) using both objective and patient-reported outcomes.

Eligible patients with diagnosed urodynamic stress incontinence (USI) were enrolled in the trial from eight specialist centres: three from UK, two from Switzerland, and one from Ireland, Greece and Slovenia, respectively. The study followed the Declaration of Helsinki for research and was approved by appropriate Ethics Committees. Patients who met inclusion criteria and signed informed consent were randomly allocated into active and sham group with 2:1 ratio. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered sealed envelopes. The sample size driver of this study is the primary efficacy hypothesis. Sample size was estimated using a success estimate of 60% for the active arm (taken from published literature describing treatments with similar mechanism of action) and 30% for the sham arm. This yielded a sample size of 69 active and 35 sham patients for 81% power (together 104 patients). To compensate for the expected 15% drop-out rate, a total of 120 patients were expected to be recruited in this trial. The active group received an active laser therapy using the Er:YAG laser (IncontiLase® protocol, Fotona, Slovenia), while the sham group received treatment with a sham hand piece in which the laser light was physically blocked from reaching the tissue. This was a single blind clinical trial with the participants being blinded to allocation. Participants received two treatments one month apart performed by trained medical personnel. Data was collected at baseline and 6 months (and 12 months in the active group) and included 1h pad weight test and questionnaires for assessment of SUI severity, sexual function and quality of life which included; leakage frequency as recorded by 3-day bladder diary, cough stress test in standing and lithotomy position, International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form (ICIQ-UI SF), The Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire short form (PISQ-12), the King’s Health Questionnaire (KHQ) and Patient Global Impression of Improvement (PGI-I). Primary outcome measure was standardized 1h pad weight test at 6-month follow up, where a treatment success was defined as a change in pad weight at 6 months follow-up that represented a > 50% reduction in the used pad weight recorded at baseline (as per FDA guidelines). Patients were monitored for discomfort and adverse effects during the treatment and follow-up periods.

110 patients with SUI were recruited between October 2015 and October 2019, 73 were in the active group and 37 in the sham group. Summary of the results is presented in Table 1. A treatment success (> 50 % reduction in pad weight) was observed in 36 % of patients from sham group (n=12), and in 58 % of patient in active group (n=33). Analysis of the primary outcome (Figure 1, Table 1) concluded that the odds of treatment success was approximately three times greater in the active arm vs the sham arm (OR 3.11, 95% CI 1.15-9.06, p-value = 0.03). The results were similar after adjustment for key prognostic factors, or exclusion of severe cases (baseline pad weight > 50g). Similarly, the geometric mean of pad weights at 6 months in the active arm was 78% less than that of the the sham arm (ratio of geometric means estimated with a log-linear model with adjustment for baseline pad weight = 0.22, 95% CI 0.09 to 0.53, p < 0.001). Data on primary outcome was not available for 20 patients (pad test was not performed in 6 patients, 2 patients were lost to follow-up, 2 patients missed their follow up appointment and 4 patients discontinued treatment. 1 patient was incorrectly randomized). Results of KHQ, PISQ-12 and PGI-I showed that the odds of improved patient outcomes are significantly greater in active arm relative to sham study arm (Table 1). Despite the median value of average number of leakages being notably reduced in active arm as compared to sham (1.16 in active vs. 0.5 in sham) (Table 1), the Incidence Rate Ratio (IRR) for the number of leaks was 0.70 (95% CI 0.45–1.11, p = 0.125), which suggests a benefit, though the observed data were not inconsistent with a null hypothesis of no effect. Nevertheless, only 12.5% of patients (n=2) recorded treatment success (measured as a > 50 % reduction in leakage episodes) in sham group, as opposed to 57 % in active group (n=21). Similarly the analysis of ICIQ scores showed that the odds of a higher value on the ICIQ was lower in the active vs the sham arm (OR = 0.50, 95% CI 0.22 to 1.10, p = 0.084). 
21 patients reported adverse events that were classified as possibly or probably related to device or intervention. 16 of these were patients in the active and 5 in the sham arm. Patients reported discomfort in vaginal and vulvar area, vaginal discharge, suspected UTI or vulvitis, itching, edema, discomfort during treatment and a single incidence of small abrasion at introitus. The reported adverse effects were all anticipated and were mostly graded as mild and required no management or were managed with cranberry capsules, NSAIDs, local anti-inflammatory cream or estrogen cream. In one patient a UTI was suspected and treated with antibiotics. The adverse effects were transient and most frequently resolved in up to 8 days’ time.

This study demonstrates that the non-ablative Er:YAG laser therapy improves SUI symptoms significantly better than sham treatment as measured by the standardized 1h pad weight test and several patient reported outcomes.

Transvaginal laser therapy has been gaining a worldwide popularity in recent years also in the field of gynaecology and urogynaecology. Despite prospective clinical trials reporting results on treatment of various gynaecological indications, robust placebo controlled clinical trial performed to assess their efficacy and safety have been scarce [1]. It is important to recognise the wide differences in energy based devices and laser in particular. This is the first multicentre placebo controlled single blinded trial to date performed to examine effect of laser therapy for SUI and we show that non-ablative Er:YAG laser therapy is beneficial for SUI, however its success depends on initial severity of incontinence symptoms with minimal adverse effects observed and reported elsewhere [2]. We can conclude that non-ablative Er:YAG laser therapy should be offered as a non-surgical treatment option for patients suffering from SUI.

C. Phillips, T. Hillard, S. Salvatore, P. Toozs-Hobson, and L. Cardozo, “Lasers in gynaecology,” European Journal of Obstetrics and Gynecology and Reproductive Biology, vol. 251. Elsevier Ireland Ltd, pp. 146–155, 01-Aug-2020.
M. Gambacciani et al., “Safety of vaginal erbium laser: A review of 113,000 patients treated in the past 8 years,” Climacteric, vol. 23, no. sup1, pp. S28–S32, Oct. 2020.