Original article
Prostate cancer treatment by the latest focal HIFU device with MRI/TRUS-fusion control biopsies: A prospective evaluation

https://doi.org/10.1016/j.urolonc.2018.05.022Get rights and content

Highlights

  • Evaluate the use of the latest technology in focal therapy of prostate cancer.

  • Targeted and systematic re-biopsy was provided for oncologic outcome.

  • Re-biopsy detected tumor persistence despite negative multiparametric magnetic resonance imaging.

  • Patient-reported outcome reveals slight decrease in potency.

  • Patient selection and knowledge of pitfalls are critical for successful ablation.

Abstract

Objectives

Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided focal high intensity focused ultrasound (HIFU) therapy of the prostate has recently been developed as a selective HIFU-therapy technique to enable targeted ablation of prostate cancer. Here we report a series of patients treated with focal HIFU therapy, discuss its potential pitfalls, and address controversies concerning the indications.

Materials and Methods

This single-center prospective study reports outcomes of patients treated from September 2014 to March 2016. Follow-up was a minimum of 12 months. MRI/TRUS-fusion-guided HIFU was performed under general anesthesia using the Focal One® device (EDAP, France). A control biopsy at 12 months was taken using the MRI/TRUS-fusion biopsy platform Artemis™ (Eigen, California) combining targeted and systematic cores. Prostate-specific antigen (PSA) changes from baseline, patient-reported outcome measures, and complications using the Clavien–Dindo classification system are also reported.

Results

Twenty-four patients (PSA < 10 ng/ml, n = 17 Gleason 3+3, n = 7 Gleason 3+4) with either unifocal or bifocal prostate imaging reporting and data system (PI-RADS) 3–5 lesions (n = 19) or without a PI-RADS lesion (n = 5) were treated. Nineteen patients underwent focal HIFU, five patients zonal HIFU. Of the 20 patients that had biopsies at 12 months, 8 patients had a positive biopsy within the ablation zone (overall cancer free rate: 60%). Using different definitions of clinically significant cancer, the cancer-free rate for the ablation zone varies between 75% and 95%. Four of the eight patients (all persistent Gleason 3+4 or upgrading to 4+3) underwent a radical whole gland salvage therapy. Patient-reported outcome measures showed no significant decrease in urinary continence (expanded prostate cancer index composite -26 urinary incontinence: P = 0.080), but there was a reduction in potency (International index of erectile function in preoperatively potent patients: median decrease of 2 points to a median of 19 points at 12 months; 95% confidence interval: 15.79–22.21; P = 0.044). Only one complication > grade II occurred.

Conclusions

Targeted MRI/TRUS fusion-guided focal HIFU allows local tumor ablation, but is not free from limitations. The procedure has good functional outcomes and a quick recovery. Multicenter trials with more patients are required to determine the procedure´s role in the prostate cancer therapy algorithm.

Introduction

Prostate cancer (CaP) in men represents the main cancer cause of years lost due to disabilities in most European countries [1]. Theoretically, focal therapy of CaP enables both cancer control and low treatment related side effects, leading to a reduction of years lost due to disabilities.

The concept of magnetic resonance imaging (MRI)-guided focal therapy is based on MRI-visible suspicious prostatic lesions. The optimized image acquisition of the prostate using multiparametric magnetic resonance imaging (mpMRI) has led to the development of magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) image fusion platforms to allow targeted prostate biopsies of suspicious lesions [2]. They both allow selection of patients as candidates for focal therapy. Different focal therapy techniques have been tested in clinical trials for tumor ablation, including high intensity focused ultrasound (HIFU), irreversible electroporation, cryotherapy, laser ablation, and brachytherapy. Until recently, most published HIFU series used cognitive fusion to target the lesion [3], [4]. Not only for fusion biopsies but also in focal therapy, image fusion has recently been introduced to support targeting the lesion [5], [6]. The latest HIFU devices utilize elastic fusion of MRI, spatial biopsy core information of the fusion biopsy platform, and TRUS imaging for focal treatment planning. This accurate navigation enhances the precision of targeting lesions by HIFU. First results with short-term follow-up showed a low morbidity with good preservation of continence and potency [5], [7].

This article reports the functional and oncologic results of a series of treated patients. The descriptions of workflow and potential pitfalls of this therapeutic option are intended to guide through the procedure for shared-decision making and interpretation of outcomes of prospective clinical trials. In the growing landscape of focal therapy platforms, detailed descriptions further facilitate comparisons between platforms and techniques.

Section snippets

Patients

Patients underwent focal or zonal HIFU of CaP using the HIFU platform Focal One® (EDAP, France) at Mannheim University Medical Center. All patients were treated within prospective clinical trials approved by the respective Ethics Committees and registered at germanctr.de. (DRKS00007105, DRKS00009021) All patients gave written informed consent. Eligibility criteria were prostate-specific antigen (PSA) < 10 ng/ml and Gleason score ≤3+4 for all patients, and either ≤2 cancer positive prostate

Study population

Twenty-four patients were treated from September 2014 to March 2016 with a minimum of 12-months of follow-up. No patient was lost to follow-up. Demographics are presented in Table 1. A detailed description of all patients is given in Table S1. Preoperatively, 10 patients did not undergo a re-biopsy on a fusion platform when the mpMRI lesion location was either in accordance with the systematic transrectal biopsy (n = 5) or no lesion was observed on mpMRI (n = 4). One patient did not undergo an

Discussion

With an increasing number of platforms proposed for focal ablation of CaP and the marketing of focal ablation by industry players, more patients seek focal therapies to circumvent the potential functional drawbacks of whole-gland treatment. The National Cancer Institute estimates that focal therapies may encompass up to 25% of all CaP treatments in the coming years [10]. It is therefore of utmost importance to perform detailed analysis of the different treatment modalities and platforms, such

Conclusions

Using a precise follow-up with targeted and systematic biopsies in all patients, 40% of the patients had a positive in-field biopsy at short-term follow-up. These results show that, despite a strict pre-HIFU selection with MRI imaging and targeted and/or systematic biopsies, MRI/TRUS-guided HIFU represents an investigational therapy with technical pitfalls. They further underline the need for biopsy follow-up of patients after focal treatment even in case of negative mpMRI findings. Therefore,

Acknowledgment

We thank Prof. Joachim Thüroff for critical review of the manuscript. We would also like to acknowledge our study nurse Simone Zendler for supporting the course of the study. The work is supported by the H.W. & J. Hector Foundation Weinheim, Germany.

Conflict of interest

D. Baumunk reports personal fees from EDAP, France, during the conduct of the study. All other authors declare no conflict of interest.

References (22)

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    The authors report a failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival of 88%, 98%, 100%, and 99%, respectively, with a 2% incontinence rate. Although erectile function was not assessed in this study, other series report 78–98% rate of erectile function preservation [14–16]. A meta-analysis of data from four studies showed that patients undergoing HIFU were at increased risk of biochemical failure when compared to Extended Beam Radiation Therapy (EBRT) at one-year follow-up which was statistically significant but this difference was no longer statistically significant at five years [17].

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1

Present address: Outpatient Urology Practice, Eugen-Adolff-Str. 1, 71522 Backnang, Germany.

2

These authors contributed equally to this work.

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