Simple SummaryA prospective institutional study was conducted at the Institute of Oncology in Ljubljana. The main objective of the study is to determine the safety and feasibility of electrochemotherapy in the treatment of vulvar cancer recurrence. From July 2020 to January 2023, 10 patients with vulvar cancer recurrence were enrolled in our study. Patients were treated with an intravenous application of bleomycin, and 8 min later, electric pulses were applied locally to the tumor to increase the cytotoxicity of bleomycin. The treatment could be performed in all patients, demonstrating its feasibility, and no adverse effects were documented, proving that the treatment is safe. In conclusion, this is the first prospective study of electrochemotherapy in the treatment of local vulvar cancer recurrence conducted for nonpalliative purposes, demonstrating its safety and feasibility.AbstractElectrochemotherapy is a local ablative therapy used for the treatment of various superficial and deep-seated tumors. Electrochemotherapy involves the application of electric pulses locally to tumors to destabilize cell membranes and facilitate the entry of cytotoxic drugs, thereby enhancing their cytotoxicity locally. The aim of our study is to investigate the safety and feasibility of electrochemotherapy in patients with vulvar cancer recurrence used for nonpalliative purposes. Ten patients with single local vulvar cancer recurrence were treated with intravenous bleomycin, followed by a local application of electric pulses (electrochemotherapy) to the tumor. Adverse events were determined using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The feasibility of treating vulvar cancer with electrochemotherapy was determined by an appropriate selection of electrodes based on the size and location of the tumor with safety margins included. Electrochemotherapy was feasible in all patients. No electrochemotherapy-related or other serious adverse events occurred. Our data suggest that electrochemotherapy is a feasible and safe technique for the treatment of vulvar cancer recurrence for nonpalliative purposes. Based on our results, electrochemotherapy might be a viable therapeutic tool for patients who would otherwise undergo surgery involving a mutilation of the external genitalia.