A prospective, randomized, single-blinded study evaluating the effect of frozen-section directed excision on positive surgical margins in high-grade vulvar dysplasia.

Abstract

TPS5644 Background: Vulvar cancer accounts for 2-5% of gynecologic malignancies. As with many skin cancers, vulvar cancer is preceded by a dysplastic state. Currently, wide local excision (WLE) is the surgical treatment modality used to excise visually dysplastic tissue, with a 0.5 cm border. However, this methodology does not incorporate the risk of microinvasion and positive margins on the tissue sample. The significance in having positive margins is a 3-fold higher risk of recurrence when positive margins are present. Our study seeks to compare this current standard of care with a frozen section directed excision, which is similar to Mohs Surgery, a long-established surgical technique mainly used in dermatology. This technique allows for repeated pathologic evaluation to ensure negative margins are present before cessation of the surgery. The goal of this study is to show the superiority of Frozen-Section Directed Excision (FSDE) in conducting vulvectomies in reducing positive margin rates, thus potentially reducing recurrence rates. Methods: This is a prospective randomized, single-blinded study. The target population is adults ≥ 18 years of age with histological or cytological confirmation of VIN 2, VIN 3, VIN 2/3 or High-grade Dysplasia NOS with a planned excisional procedure, with high suspicion by the enrolling investigator that gross surgical margins of ≥ 3 mm can be achieved without laser or other destructive procedures. One group of subjects is assigned to the FSDE surgery arm and will undergo this procedure. The other group of subjects will be assigned to the WLE (standard of care) arm and will undergo that procedure. The randomization will be 1:1. This trial is designed as a group sequential study with two primary analysis timepoints. The interim analysis will occur after the surgical margin status is known for the first 56 evaluable subjects and the second after all (112 targeted) evaluable subjects. Information regarding the surgery procedure, the amount of time the surgery procedure takes, and total amount of pain medication required during surgery and while in the surgery recovery area will be collected. The study team will also look at recurrence rates in six months, if any other therapies are required, and subject satisfaction related to the surgery, recovery, and sexual function by using questionnaires before and after the procedure. Based on previously published cases and a review of cases of vulvar excision at our institution, it is anticipated that the rate of positive margins will exceed 50% with standard surgery. It is expected that FSDE will reduce the positive margin rate by at least 50%. Assuming 56% of standard surgeries result in positive margins and a two-tailed alpha of 0.05, 56 subjects per arm or a total of 112 evaluable subjects will provide 80% power to detect this difference. Clinical trial information: NCT05934851 .