Safety and Feasibility of Endoscopic-Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: An Exploratory Randomised Clinical Trial.

BACKGROUND: Locally advanced rectal cancer (LARC) has high recurrence rates despite aggressive multimodal treatment with neoadjuvant chemoradiotherapy (CRT) followed by surgery. Electrochemotherapy (ECT), combining electroporation with chemotherapy, has shown safety and feasibility in other malignancies, but its role as an additive neoadjuvant treatment in rectal cancer remains unexplored. METHODS: In this parallel-group, randomised safety and feasibility trial, patients with histologically verified LARC who completed neoadjuvant CRT were randomised 1:1 to a single ECT treatment with bleomycin before surgery (n = 8) or standard therapy (n = 8). The primary outcome was safety (amended from the protocol-specified efficacy endpoint after early study termination). Follow-up was scheduled before surgery and at 6 and 12 weeks post-surgery, including adverse events, clinical examination, and patient-reported quality of life, bowel, urinary, and sexual function. RESULTS: ECT was successfully delivered in all treated patients. Median procedure time was 23.5 min. Adverse events occurred in all ECT patients, predominantly rectal pain (86%), with one patient hospitalised for pain management. No procedure-related complications were observed. Two ECT patients had R1 resections due to intraoperative perforations. Tumour response was heterogeneous: two patients achieved complete response (TRG1), three achieved partial response (TRG2-3), and one achieved no response; corresponding numbers in the control group were 2, 4, and 2. One ECT patient achieved clinical complete response and entered a watch-and-wait programme. Patient-reported pain worsened transiently after ECT but returned to baseline by 12 weeks post-surgery. CONCLUSIONS: ECT is a technically feasible adjunct to neoadjuvant CRT for LARC. However, its efficacy and safety, particularly regarding surgical complications, remain unclear. Larger trials are needed to determine the role of ECT in multimodal neoadjuvant treatment.