A Multicenter Single-Arm Objective Performance Criteria Trial to Determine the Efficacy and Safety of High-Frequency Irreversible Electroporation as Primary Treatment for Localized Prostate Cancer: A Study Protocol.

Bi-Ming He,Wei-Gang Yan,Zhi-En Zhou,Yi Zhou,Zhen-Kai Shi,Wei Xue,Xu Gao,Bai-Jun Dong,Yan-Qing Wang,Shuai-Dong Wang,Lei Yin,Chuan-Liang Xu,Hai Zhou,Lin-Hui Wang,Shan-Cheng Ren,Hai-Feng Wang,Heng-Zhi Lin

doi:10.3389/fonc.2021.760003

Abstract

IntroductionThe classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects.Methods and AnalysisThis is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation.Ethics and DisseminationThis study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals.ConclusionsThis multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer.Strengths and Limitations of This StudyA comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term.Clinical Trial Registration ClinicalTrials.gov, NCT03838432

Highlights

The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury
This trial will discontinue due to the following: [1] more than 20% of the total number of cases deviated from the protocol; [2] the number of dropout cases exceeds 20% of the total number of designed cases; [3] the severity and frequency of serious adverse events that occurred tended to exceed those reported in local treatment literature; and [4] the severity and frequency of instrument defects and faults exceed the acceptable risk
Student’s t test or Wilcoxon signed-rank test will be used for the comparison of quantitative data between groups; chi-square test or Fisher’s exact test will be used for categorical data; and Wilcoxon signed rank test or Cochran– Mantel–Haenszel (CMH) test will be used for ranked data

Summary

Introduction

The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. The traditional pathway for the therapy of low to intermediate-risk prostate cancer, radical prostatectomy, or radiation therapy aims to eliminate the whole gland rather than the localized cancer tissue. The treatment is efficacy, it may damage the neurovascular bundles, bladder neck, and rectum, which will lead to complications of erectile dysfunction, urinary incontinence, and bowel injury. These complications and side effects seriously reduce the quality of life. It will bring psychosocial and financial burdens for patients who were under active surveillance for a long period of time

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