French multicentre randomised phase III trial evaluating the efficacy and safety of vaginal radiofrequency in the management of vulvovaginal atrophy and dryness in patients treated for breast cancer (RF-Vaginale): trial protocol.

introductionSymptoms associated with vulvovaginal atrophy affect up to 73% of patients with breast cancer, whether menopausal or non-menopausal, because certain breast cancer treatments are responsible for oestrogen deprivation on the genital tract. These symptoms are currently underdiagnosed and undertreated but can significantly impair the quality of life and can be a cause of premature discontinuation of adjuvant hormone therapy. Treatment of vulvovaginal atrophy in patients managed for breast cancer should be the first-line treatment with non-hormonal local moisturising therapy. However, this treatment is often insufficient. Systemic menopause hormone treatment is not indicated and local oestrogen treatment is not a first-line treatment in this neoplastic context. Therapeutic alternatives, such as vaginal radiofrequency (RF) treatment, could be considered. Vaginal RF increases collagen synthesis by stimulating fibroblasts. However, the vaginal RF has not been sufficiently evaluated in the literature. We hypothesised that vaginal RF can improve a patient's experience of vaginal dryness after breast cancer treatment when first-line local moisturising treatment is insufficient. METHODS AND ANALYSIS: The RF-Vaginale trial will be a multicentre randomised phase III trial in two parallel groups until the 6-month assessment comparing a reference treatment with local moisturising (hyaluronic acid-based treatment, three times a week) versus the experimental treatment combining reference treatment+vaginal RF treatment. The vaginal RF treatment will consist of three sessions spaced 4-6 weeks apart (MATMATECH, GynWave 360). The primary outcome will be vaginal dryness, assessed at 6 months using a patient-rated 0-10 numerical scale. The secondary outcomes will be dyspareunia and Vaginal Health Index Score (VHIS). Dyspareunia will be assessed by the patient using a patient-rated 0-10 numerical scale, in patients reporting a sexual life with a male partner engaged in vaginal intercourse. The VHIS will be assessed by a physician blinded to the treatment group. All outcomes will also be evaluated at 3 and 12 months.This trial will be proposed to a population receiving an adjuvant treatment for breast cancer with an aromatase inhibitor ±luteinising hormone-releasing hormone (LHRH) agonist.The primary analysis will focus on the evaluation of the mean difference in vaginal dryness score at 6 months between arms, adjusted for baseline value, patient age (<50 vs 50-54 vs 55-64 vs ≥65) and type of hormone therapy (anti-aromatase with vs without LHRH agonist), estimated using an analysis of covariance model. Assuming a SD of 4.5 for the score at 6 months, 71 patients need to be analysed to ensure an 80% power if the difference between the groups is 3, the test being performed at the two-sided alpha threshold of 0.05. Assuming a 5% rate of non-evaluable patients at 6 months, we plan to recruit a total of 75 patients. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee (CPP Sud Est I, 12 November 2024), complied with the Declaration of Helsinki and French laws and regulations, and followed the International Conference on Harmonisation E6 Guideline for Good Clinical Practice (reference number EMA/CHMP/ICH/135/1995). The trial results, even if inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06900374.