Clinical trial NCT04113811: Microwave Needle Thermoablation for Treatment of Localized Prostate Cancer
Official title: Microwave Needle Thermoablation for Treatment of Localized Prostate Cancer Under the Guidance of MRI-Ultrasound Fusion Organbased Tracking: A Phase 2 Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostate cancer
Focal therapy
Microwave ablation
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2019-10-03
Enrollment: 30
Sex: MALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The oncological control of prostate cancer
timeFrame: At 6 months after treatment
Secondary outcomes:
measure: Per-patient analysis of any cancer detected on biopsy of any ablated areas
timeFrame: At 6 months after treatment
measure: Cancer detection on biopsy of each ablated MRI visible lesion
timeFrame: At 6 months after treatment
measure: Cancer detection on biopsy of each ablated MRI invisible lesion
timeFrame: At 6 months after treatment
measure: Gleason 4 or 5 cancer detected on biopsy of ablated area
timeFrame: At 6 months after treatment
measure: Out-of-field recurrence: Any cancer outside treated area on systematic biopsy
timeFrame: At 6 months after treatment
measure: Common Terminology Criteria for Adverse Events (CTCAE) v5.0
timeFrame: 1 year
measure: Dimension of necrosis area on MRI
timeFrame: At 1 week
measure: PSA change
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: International Prostate Symptom Score (IPSS) score
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: Sexual side effects, up to 1 year, measured by International Index of Erectile Function 5-item version (IIEF-5) score
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: Expanded Prostate cancer Index Composite (EPIC-26) questionnaire
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: Common Terminology Criteria for Adverse Events (CTCAE) rectal toxicity
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: EQ-5D (EuroQol 5 dimensions) questionnaire
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
measure: QLQ-C30 (Quality of life Core 30) questionnaire
timeFrame: At baseline, 4 weeks, 3 months, 6 months and 12 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital, Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Peter KF Chiu, MBChB,FRCSEd
role: PRINCIPAL_INVESTIGATOR
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