Feasibility and Safety of Transurethral HIFU in Various Prostate Diseases; Particularly Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Radiologically determined treatment accuracy of HIFU ablation in BPH arm/group.
研究概览
简要总结
This study assesses feasibility and safety, the primary outcomes, of MRI guided transurethral high intensity focused ultrasound (HIFU) ablation for prostate diseases (PD). We will enrol 10 patients to each group with criteria as follows: localised prostate cancer (PC); locally advanced PC; locally recurrent PC after external beam radiation therapy (EBRT); benign prostatic hyperplasia (BPH). Secondary outcomes are both oncologic and functional outcomes and imaging based follow up after HIFU therapy will be also assessed.
详细描述
Prostate cancer (PC) is the most common cancer among men in Finland with the highest incidence of all cancers. Benign prostate hyperplasia (BPH) also has high prevalence, increasing with age. BPH may cause harmful lower urinary tract symptoms (LUTS) and it is demonstrated that by the age of 60, over 50 % of men have clinically significant prostate BPH and up to 40 % of men over age 60 suffer from LUTS.
Currently curative intended therapies for PC, radiation therapy (RT) and radical prostatectomy (RP), offer desirable oncologic local control but have major impact on genitourinary function and quality of life (QoL). Some patients are unfit for surgical procedures or cannot tolerate RT due to concomitant medical conditions or prior therapies. At present lower risk PC is increasingly managed with active surveillance. However, diagnosis of PC and active surveillance itself may both lead to notable psychological and emotional burden impairing QoL. Further, significant amount of cases in some point end up in radical treatment resulted from either risk profile upgrade or patients preference. For these patients optimal treatment might be a focal therapy with sufficient oncologic control and minor impact on QoL.
There is controversy related to optimal treatment in local recurrence after RT. 45% of patients will have local recurrence after RT within 8 years after treatment. Androgen deprivation therapy (ADT) decelerate disease only temporarily and salvage RP includes major risks and is technically demanding, but can provide long-term cure in selected patients.
On the aspect of palliation, there is an eminent need for less invasive supplementary therapies since patients presenting with metastatic or locally advanced PC, generally have low performance status.
Management of benign prostatic obstruction has also faced challenges with conventional treatment modalities, since ageing and profuse co-morbidities among patients have increased. Transurethral resection of prostate (TURP) is still the standard treatment in severe LUTS caused by BPH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Shared inclusion criteria for all groups:
- •Language spoken: Finnish, English or Swedish
- •Mental status: Patients must be able to understand the meaning of the study
- •Informed consent: The patient must sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff.
- •Potential prostate biopsies obtained > 6 weeks before HIFU/TULSA-PRO treatment (or at the discretion of PI)
- •Eligible for MRI
- •Eligible for spinal or general anesthesia (ASA 3 or less)
- •Succession of urethral catheterization/Patency of prostatic urethra confirmed if needed with pre-HIFU cystoscopy
- •Group-specific inclusion criteria
- •Localized PC prior to RP
- •All localized PC patients planned for robot assisted laparoscopic prostatectomy (RALP) with normal standards of care are eligible for this study (EAU guidelines)
- •MRI-visible biopsy proven PC (biopsies obtained < 6 months before treatment)
- •Locally symptomatic locally advanced and/or metastatic prostate cancer in need of palliative surgical intervention
- •gross recurrent hematuria
- •bladder outlet obstruction with intractable symptoms
- •urinary retention
- •Locally recurrent PC after EBRT as a salvage approach
- •Phoenix criteria of biochemical relapse (PSA nadir + 2 ng/ml)
- •MRI-visible, biopsy proven local recurrence
- •No evidence of distant metastasis in PSMA-PET/CT
- •Symptomatic BPH with need for intervention
- •Patients planned for surgical procedure (e.g. TURP, laservaporization or open adenomectomy) with normal standards of care are eligible for this study
- •Bilobular hyperplasia (enlarged transition zone lobes) without dominant enlargement of periurethral zone "median lobe" assessed in cystoscopy and TRUS
- •No suspicion of cancer on baseline MRI (PI-RADS v2 lesion < 3)
排除标准
- •for all groups:
- •Prostate calcifications >1cm in largest diameter located in the anticipated treatment sector on baseline TRUS or MRI
- •Prostate cysts >1cm in largest diameter located in the anticipated treatment sector on baseline TRUS or MRI
- •History of chronic inflammatory conditions (e.g. inflammatory bowel disease) affecting rectum (also includes rectal fistula and anal/rectal stenosis)
- •Contraindications for MRI (cardiac pacemaker, intracranial clips etc.)
- •Uncontrolled serious infection
- •Claustrophobia
- •Hip replacement surgery or other metal in the pelvic area
- •Severe kidney failure (glomerular filtration rate (GFR) <30ml/min/1.73m2) exclude usage of gadolinium in contrast-enhanced imaging unless justifiable based on the clinical judgment of the responsible radiologist and/or urologist.
- •Known allergy to gadolinium
- •Known allergy or contraindication to GI anti-spasmodic drug (e.g. glucagon, buscopan)
- •Inability to insert urinary catheter (i.e. urethral stricture disease)
- •Patients with artificial urinary sphincter, urethral sling or any penile implant
- •Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist
研究组 & 干预措施
Localised PC prior to RP
MRI guided transurethral HIFU ablation is targeted to MRI visible, biopsy proven, index lesion(s) within prostate and if possible with 5mm angular extension (imaging based healthy tissue marginal) to both sides from the tumour boundary in transverse plane and 5 mm in coronal plane. The ablative effect is aimed to reach prostate capsule by heating the control boundary (3 mm from capsule) to temperature 57 °C. The focal approach is intended to be radical as for index lesion.
干预措施: MRI guided transurethral HIFU ablation of prostatic tissue (Device)
Symptomatic locally advanced PC
MRI guided transurethral HIFU ablation is targeted to main prostatic malignant tumour squeezing and/or invading the prostatic urethra and/or bladder neck. The approach is intended to be palliative.
干预措施: MRI guided transurethral HIFU ablation of prostatic tissue (Device)
Locally recurrent PC after EBRT
MRI guided transurethral HIFU ablation is targeted to MRI visible, biopsy proven, local recurrent index lesion(s) within and/or surrounding prostate and if possible with 5 mm angular extension to either side from the tumour boundary in transverse plane and 5 mm in coronal plane. The approach is intended to be focal and salvage.
The whole-gland HIFU ablation approach will be considered in case of extensive organ confined recurrent prostate cancer (positive biopsies for malignancy from extensive/multiple area in prostate and/or extensive/multiple lesion(s) at baseline MRI) to cover whole prostate.
干预措施: MRI guided transurethral HIFU ablation of prostatic tissue (Device)
Symptomatic BPH
MRI guided transurethral HIFU ablation is targeted to adenomas of the prostate. The HIFU sector encompasses bilateral (anterolateral) transitional zones between bladder neck and verumontanum (colliculus seminalis).
干预措施: MRI guided transurethral HIFU ablation of prostatic tissue (Device)
结局指标
主要结局
Radiologically determined treatment accuracy of HIFU ablation in BPH arm/group.
时间窗: 12 months from the treatment date
Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy. The ratio in percentage between target prostate volume (ml) and NPV (ml) will be measured.
Radiologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
时间窗: 3-4 weeks from the treatment date
Quantitative analysis of radiologically verified treatment accuracy; determined by comparing targeting volumes on MRI during treatment planning to immediate, 1 and 3 week NPV in CE-MRI following HIFU therapy. The ratio in percentage (%) between target prostate volume (ml) and NPV (ml) will be measured.
Radiologically determined treatment accuracy of HIFU ablation in locally recurrent PC after EBRT arm/group.
时间窗: 12 months from the treatment date
Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy. The ratio in percentage between target prostate volume (ml) and non-perfused volume (ml) will be measured.
Evaluate targeting accuracy volume of HIFU ablation separately in each study arm/group.
时间窗: The date of HIFU treatment
Quantitative analysis of targeting accuracy volume illustrates over- and under-treatment representing the amount of tissue ≥ target temperature 57°C outside the target volume and \< target temperature 57°C inside the target volume, respectively. Over- and under-treatment volumes are expressed as a % of the target volume. The measure is a composite outcome measure reported as single value for each arm/group.
Safety of MRI guided transurethral HIFU ablation in various prostate diseases
时间窗: 12 months from the treatment date
Safety is determined in each group and all group together by evaluation of the frequency and severity of device/treatment related adverse events associated with the use of TULSA-PRO system to ablate prostate tissue. The severity of the adverse events are graded according to the Clavien-Dindo Classification of surgical complications. The measure is a composite outcome measure reported as single value for each arm/group.
Evaluate targeting accuracy of HIFU ablation separately in each study arm/group.
时间窗: The date of HIFU treatment
Quantitative analysis of targeting accuracy is defined as spatial difference between target prostate region in treatment planning phase and the target temperature isotherm (57°C) at the end of HIFU treatment on MRI thermometry. The measure used is dice similarity coefficient (DSC - unitless from 0 to 1) which is a statistical validation metric to measure the degree of spatial overlap between two regions. The measure is a composite outcome measure reported as single value for each arm/group.
Radiologically determined treatment accuracy of HIFU ablation in locally advanced PC arm/group.
时间窗: 12 months from the treatment date
Quantitative analysis of treatment accuracy; determined by comparing targeting volume on MRI during treatment planning to immediate, 1 week and 12 months NPV in CE-MRI following HIFU therapy. The ratio in percentage between target prostate volume (ml) and NPV (ml) will be measured.
Histopathologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
时间窗: 3-4 weeks from the treatment date
Qualitative analysis of treatment accuracy; determined by comparing both targeting volume on MRI during treatment planning and immediate, 1 and 3 weeks NPV following HIFU therapy separately to histopathologically verified coagulation necrosis volume from the removed prostate at 3 week after HIFU therapy. The ratio in percentage between target prostate volume (ml) and NPV (ml) to coagulative necrosis volume (ml) will be measured.
次要结局
- Preliminary efficacy of HIFU ablation to achieve sufficient tumour control in patients having local recurrent PC after EBRT(12 months from the treatment date)
- Image based follow up following HIFU ablation(12 months from the treatment date)