Microwave Needle Thermoablation for Treatment of Localized Prostate Cancer

Study Overview
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Brief Summary
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Conventional treatment options for localized prostate cancer include prostatectomy, radiotherapy and active surveillance. However, prostatectomy and radiotherapy carry certain degree of morbidity, including the risks of urinary incontinence, erectile dysfunction and injury to the surrounding organs like rectum and bladder. Active surveillance carries the risk of disease progression and psychological distress to the patients. Focal therapy employs the concept of only destroying the target lesion without treating other benign areas, resulting in disease cure in majority of cases with less treatment morbidity. Microwave treatment to the prostate has been performed since more than 20 years ago for benign prostatic hyperplasia and is approved by FDA in United States. It exerts its effect through thermal destruction of prostate tissue. Targeted treatment of localized prostate cancer using microwave needle ablation guided by MRI and Ultrasound imaging has been performed recently and was shown to be safe and effective. Our study aims to assess the effectiveness of this focal therapy in treating localized prostate cancer.

Detailed Description
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Prostate cancer screening with Prostate specific antigen (PSA) has resulted in an increase in the diagnosis of localized prostate cancer. The traditional approach for treating low-risk and intermediate-risk prostate cancer includes definitive treatment with either radical prostatectomy or radiotherapy, both of which are associated with considerable morbidity mainly in the area of genitourinary and bowel complications. Active surveillance is one of the options for early low grade prostate cancers, but about half of these men would convert to radical treatment in 10 years' time. In the case of localized intermediate risk prostate cancer, active surveillance is not a good option as it is associated with inferior oncological outcomes in subsequent radical treatment Focal therapy for localized prostate cancer is the middle ground between active surveillance and radical treatment like prostatectomy or radiotherapy. Instead of monitoring a tumor to see when it is going to progress, focal therapy ablates the target lesion with the aim to reduce or avoid radical treatment. Although the efficacy of focal therapy appeared to be inferior to radical treatment with higher recurrence rates of 20-50%, repeated focal treatment is feasible and the complication profile of focal therapy was significantly better. A recent publication showed that in men with majority intermediate risk prostate cancer, 5 and 8-year freedom from radical treatment was 91% and 81%. This avoids the majority of patients with localized prostate cancer from receiving a radical treatment with potential complications. A recent consensus panel agreed that focal therapy should be defined as ablation of the dominant or index lesion only . Numerous energy modalities have been utilized for focal therapy of prostate cancers, including High-intensity focused ultrasound (HIFU), Cryotherapy, Photodynamic therapy (PDT), Focal laser ablation (FLA), irreversible electroporation (IRE), and focal brachytherapy. All of them are still being considered experimental according to the latest international guideline due to inferior oncological outcomes (high recurrence and retreatment rates) and lack of long term data. The targeting mechanisms during focal therapies are largely cognitive after the operator read the MRI, resulting in limited precision and possible over or under-treatment. Under-treatment would result in residual disease and treatment failure, while over-treatment might result in complications similar to that in radical treatment. The limitation of MRI in revealing all significant tumors in the prostate and the inability to treat MRI-invisible tumors using existing focal therapy platforms also contributed to treatment failure. However, there is still a significant amount of focal therapies being performed worldwide due to its lower overall morbidity than radical treatment, feasibility of repeated focal treatment, and feasibility to proceed to radical treatment in treatment-failure cases. Microwave treatment to prostate, Transurethral microwave therapy (TUMT), has been performed since more than 20 years ago for benign prostatic hyperplasia as an office procedure under local anaesthesia. It has not been used in prostate cancer treatment until recently a group in France conducted a single arm pilot study using organ-based tracking (OBT) MRI-Ultrasound fusion-guided microwave therapy using Koelis system for focal treatment of prostate cancer. (Clinical Trials number: NCT03023345) The treatment was done in 10 patients using microwave needles via transrectal route under general anaesthesia, with the primary outcome of complete necrosis of the index tumour on prostate MRI on day 7. The results were being reported in a conference paper, showing 80% (8/10) cases with complete necrosis of index tumor on day-7 MRI, and 20% (1/5) targeted biopsy of tumor showing residual low grade cancer at 6 months. No adverse event or complication occurred in all 10 cases. MRI-Ultrasound fusion-guided prostate needle biopsy has been performed transperineally in Prince of Wales Hospital under routine basis. In this study, we plan to investigate oncological outcome of fusion-guided microwave needle therapy using transperineal (TP) approach under general anaesthesia. Most focal therapy modalities treat lesion that can be seen on MRI and confirmed on biopsy. In cases where significant cancer was located only on systematic biopsy but not on MRI, half or whole gland treatment is usually needed. In the microwave needle ablation guided by organ-based tracking (OBT) MRI-Ultrasound fusion using Koelis system, the positive systematic cores that is not visible on MRI can be accurately localized at the time of biopsy using Koelis system and treated subsequently.

Official Title
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Microwave Needle Thermoablation for Treatment of Localized Prostate Cancer Under the Guidance of MRI-Ultrasound Fusion Organbased Tracking: A Phase 2 Trial.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Device: Biomedical TATO3® Microwave needle thermoablation device (Koelis, Grenoble, France)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged between 45 - 75 years Life expectancy > 10 years upon recruitment Localized low or intermediate risk prostate cancer diagnosed on MRI-Ultrasound fusion targeted biopsy Organ-confined prostate cancer on MRI PSA < 20 ng/mL At least 1 MRI visible lesion present and size ≤15mm, and Targeted biopsy showing Gleason score 6 (with cancer core length ≥6mm) or Gleason score 7 (3+4 or 4+3), With or without positive Systematic biopsy (out of 24 systematic cores) away from MRI visible target showing Gleason 6 cancer Exclusion Criteria: Patients unfit for MRI exam or MR gadolinium contrast Patients with previous treatment of prostate cancer Patients with maximal length of target lesion >15mm Patients with MRI-visible or invisible lesion within 10mm from rectum or 10mm from sphincter on MRI Patients with >3 areas (MRI-visible or invisible) of prostate cancer Patients with Gleason score 4+4 or any Gleason pattern 5 cancer Patients with bladder pathology including bladder stone and bladder cancer Patients with urethral stricture Patients with neurogenic bladder and/or sphincter abnormalities

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single-centre prospective phase 2 trial to investigate the efficacy of Microwave needle thermoablation of prostate cancer using the Biomedical TATO3® (Thermal Ablation Treatments for Oncology 3) ablation system in patients with localized prostate cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microwave needle thermoablation of prostate cancer<br>The treatment will be performed under general anaesthesia or monitored anaesthetic care using the Biomedical TATO3® Microwave needle thermoablation device (Koelis, Grenoble, France) under Organ-based Tracking® (OBT) mechanism of the Koelis Trinity® machine. Both Koelis Trinity and TATO3 are CE (European Conformity) marked in Europe. A transrectal sideview ultrasound probe is used for real-time imaging and OBT of the prostate. The TATO3® needle is inserted transperineally to the tumor under MRI-Ultrasound fusion OBT guidance with the treatment zone covering the whole tumor. The dominant MRI-visible lesion and up to 1-2 more MRI-visible or invisible lesion will be treated. | Device: Biomedical TATO3® Microwave needle thermoablation device (Koelis, Grenoble, France)<br>* In this study, we plan to investigate oncological outcome of fusion-guided microwave needle therapy using transperineal (TP) approach<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The oncological control of prostate cancer | Any cancer detected on biopsy of each ablated area | At 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-patient analysis of any cancer detected on biopsy of any ablated areas | Per-patient analysis of any cancer detected on biopsy of any ablated areas | At 6 months after treatment | 
| Cancer detection on biopsy of each ablated MRI visible lesion | Cancer detection on biopsy of each ablated MRI visible lesion | At 6 months after treatment | 
| Cancer detection on biopsy of each ablated MRI invisible lesion | Cancer detection on biopsy of each ablated MRI invisible lesion | At 6 months after treatment | 
| Gleason 4 or 5 cancer detected on biopsy of ablated area | Gleason 4 or 5 cancer detected on biopsy of ablated area | At 6 months after treatment | 
| Out-of-field recurrence: Any cancer outside treated area on systematic biopsy | Out-of-field recurrence: Any cancer outside treated area on systematic biopsy | At 6 months after treatment | 
| Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Complications of treatment using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 1 year | 
| Dimension of necrosis area on MRI | Dimension of necrosis area on MRI | At 1 week | 
| PSA change | PSA change after treatment | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| International Prostate Symptom Score (IPSS) score | Urinary symptoms measured by IPSS score, score ranging from 0-35 (the higher the worse) | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| Sexual side effects, up to 1 year, measured by International Index of Erectile Function 5-item version (IIEF-5) score | Sexual side effects, up to 1 year, measured by IIEF-5 score (ranging from 1-25), the lower the worse | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| Expanded Prostate cancer Index Composite (EPIC-26) questionnaire | Quality of life in patients with prostate cancer measured by EPIC-26, range 0-100, the higher score the better the quality of life | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| Common Terminology Criteria for Adverse Events (CTCAE) rectal toxicity | Rectal side effects measured by CTCAE rectal toxicity, Grade 1-5 for any rectal toxicity, the higher the score the more severe the toxicity | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| EQ-5D (EuroQol 5 dimensions) questionnaire | Quality of life measured by ED-5Q questionnaire, with 5 components [Mobility, Self Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression)], and a Visual analogue scale (EQ-VAS) score, the higher the score the better in quality of life | At baseline, 4 weeks, 3 months, 6 months and 12 months | 
| QLQ-C30 (Quality of life Core 30) questionnaire | Quality of life measured by QLQ-C30, score 0-100, the higher the score the better in quality of life | At baseline, 4 weeks, 3 months, 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Focal therapy, Microwave ablation