Localised Prostate CancerHIFU-PRONCT03350529
MRI Guided Transurethral HIFU for Various Prostate Diseases
A study testing MRI guided transurethral HIFU ablation of prostatic tissue in people with Localised Prostate Cancer and Locally Advanced Prostate Cancer, run by Turku University Hospital at 1 site in Finland.
Trial summary
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… Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Localised Prostate Cancer, Locally Advanced Prostate Cancer, Locally Recurrent Prostate Cancer
- What is being tested?
- MRI guided transurethral HIFU ablation of prostatic tissue
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteFinland
- Study dates
- 24 Jul 2017to 31 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
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
Group 1. 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)
Group 2. 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
Group 3. 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
Group 4. 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)
Shared exclusion criteria 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Feasibility and Safety of Transurethral HIFU in Various Prostate Diseases; Particularly Prostate Cancer
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.
Read the detailed description
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.
Recently the major development of magnetic resonance imaging (MRI) has been achieved improving PC diagnosis and local staging. Even though PC is often multifocal, evidence indicates that both clinical outcome and prognosis of PC is determined predominantly by index lesion. Because of the notable risk of morbidities involving radical treatments and significant evolution of MRI, focal therapies have attained wide interest. One of the most interesting focal mini-invasive treatment is high intensity focused ultrasound (HIFU). HIFU technique exploits thermal energy; by raising target temperature over 55°C target volume is destroyed due to acute coagulation necrosis. Modern devices delivering HIFU to the prostate are transurethral and emit directional high intensity ultrasound to the focused regions utilising superior MRI guidance compared to older generation ultrasound guidance. Magnetic resonance thermometry technique utilizes noninvasive measurement of tissue temperature allowing monitoring real time temperature changes during treatment. The MRI treatment system is equipped with active dynamic temperature feedback control designed to maintain a constant temperature inside the target volume and at the boundary of the target area. By this way conformal three-dimensional ablative volumes with great spatial accuracy and precision can be achieved simultaneously avoiding damages to the surrounding sensitive tissues. Therapy verification is confirmed instantaneously after treatment by acquiring contrast enhanced MRI (CE-MRI) that visualise the non-perfused-volume (NPV) describing the success of total ablation of the target prostate volume.
This prospective clinical single center feasibility and safety study will evaluate the role of MRI guided transurethral HIFU ablation for various PD and clinical settings. All enrolled patients have prostate pathology and different clinical situation with need of definitive interventions and they are divided to four arms/groups according to specific inclusion criterion. Group 1 localised PC prior to RP, group 2 symptomatic locally advanced PC in need of palliative surgical intervention, group 3 locally recurrent PC after EBRT and group 4 symptomatic BPH in need for intervention.
The hypothesis is that MRI guided transurethral HIFU is feasible and safe in various prostate diseases and clinical settings. If hypothesis is proven for certain or for all groups, the investigators will continue with that group or groups to phase 2 clinical multi-institutional studies.
- Conditions
- Localised Prostate Cancer, Locally Advanced Prostate Cancer, Locally Recurrent Prostate Cancer, Benign Prostatic Hyperplasia
- Being tested
- MRI guided transurethral HIFU ablation of prostatic tissue
- Keywords
- prostate cancer, benign prostatic hyperplasia, benign prostatic obstruction, high intensity focused ultrasound, real-time temperature feedback control, magnetic resonance imaging
- Medical subject headings
- Prostatic Hyperplasia, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI guided transurethral HIFU ablation of prostatic tissueDevice
Also called TULSA-PRO (Profound Medical Inc), Device: PAD-105
The technology is developed to ablate targeted benign and malignant prostate tissue through transurethrally inserted probe that transmit ultrasound energy under MRI guidance and control. The therapeutic endpoint of this method is thermal coagulation of prostate tissue.
| Study group | Role | What they receive |
|---|---|---|
| Localised PC prior to RP | Experimental | 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. Receives: Device: MRI guided transurethral HIFU ablation of prostatic tissue |
| Symptomatic locally advanced PC | Experimental | 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. Receives: Device: MRI guided transurethral HIFU ablation of prostatic tissue |
| Locally recurrent PC after EBRT | Experimental | 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. Receives: Device: MRI guided transurethral HIFU ablation of prostatic tissue |
| Symptomatic BPH | Experimental | 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). Receives: Device: MRI guided transurethral HIFU ablation of prostatic tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate targeting accuracy of HIFU ablation separately in each study arm/group.
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.
Measured: The date of HIFU treatment
Evaluate targeting accuracy volume of HIFU ablation separately in each study arm/group.
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.
Measured: The date of HIFU treatment
Radiologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
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.
Measured: 3-4 weeks from the treatment date
Histopathologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
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.
Measured: 3-4 weeks from the treatment date
Radiologically determined treatment accuracy of HIFU ablation in locally advanced PC arm/group.
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.
Measured: 12 months from the treatment date
Radiologically determined treatment accuracy of HIFU ablation in locally recurrent PC after EBRT arm/group.
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.
Measured: 12 months from the treatment date
Radiologically determined treatment accuracy of HIFU ablation in BPH arm/group.
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.
Measured: 12 months from the treatment date
Safety of MRI guided transurethral HIFU ablation in various prostate diseases
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.
Measured: 12 months from the treatment date
Secondary outcomes (2)
Preliminary efficacy of HIFU ablation to achieve sufficient tumour control in patients having local recurrent PC after EBRT
Histopathological evaluation of the treatment response is based on 2-6-core biopsy results obtained from HIFU treated region/volume at 12 months. The number of biopsies taken is depended on the size and extension of the primary lesion treated with HIFU. The cognitive transrectal ultrasound guided biopsy method will be used to confirm histologically anticipated treatment success; coagulative necrosis/fibrosis/scar tissue of the prostate tissue. The outcome of biopsies (negativity/positivity for prostate cancer) will be measured. The proportion of patients with negative prostate biopsy will be measured at 12 months follow-up visit.
Measured: 12 months from the treatment date
Image based follow up following HIFU ablation
Evaluation and characterisation of image based follow up with repetitive mpMRI (Arm/group 1: immediate, 1 and 3 week, Arms/Groups 2, 3 and 4: immediate, 1 week, 12 month) after HIFU treatment. Image based follow up will be focused on modifications and development of the rim of enhancement surrounding NPV and the evolution of NPV following HIFU treatment.
Measured: 12 months from the treatment date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start24 Jul 2017
- Primary completion31 May 2024
- Study completion31 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (48)Papers the sponsor has linked to this study.
- Other trials for Localised Prostate CancerStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This study is an early phase 1 non-randomized prospective single-institutional and four arm study to determine the applicability, feasibility and safety of MRI guided transurethral HIFU ablation of prostate separately in each pre-specified group/arm (10 patients per group). Due to the encouraging feasibility and safety results, an amendment was made to the original study protocol to increase the amount of salvage group patients and BPH group patients. With the approval of the ethics committee, the sample size of the salvage group and BPH group was increased to a total of 40 patients and 30 patients, respectively.
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- University of Turku
- Responsible party
- Sponsor
- Investigators
- Peter Boström, M.D.Ph.D, Principal investigator, Department of Urology, VSSHP, University of Turku
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03350529
- Sponsor's protocol ID
- TO3/001/17
- Acronym
- HIFU-PRO
- Status last verified
- Nov 2024
- First submitted
- 12 Oct 2017
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
1.www.cancerregistry.fi
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
PubMed 25220842Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am. 2006 Sep;44(5):689-710, viii. doi: 10.1016/j.rcl.2006.07.005.
PubMed 170302214. McDougal WS, Wein AJ, Kavoussi LR, et al: Campbell-Walsh Urology 10th Edition Review E-Book. A Saunders Title; 2011. p. 704
McNeal JE. Anatomy of the prostate and morphogenesis of BPH. Prog Clin Biol Res. 1984;145:27-53. No abstract available.
PubMed 6201879Cooperberg MR, Moul JW, Carroll PR. The changing face of prostate cancer. J Clin Oncol. 2005 Nov 10;23(32):8146-51. doi: 10.1200/JCO.2005.02.9751.
PubMed 16278465Bechis SK, Carroll PR, Cooperberg MR. Impact of age at diagnosis on prostate cancer treatment and survival. J Clin Oncol. 2011 Jan 10;29(2):235-41. doi: 10.1200/JCO.2010.30.2075. Epub 2010 Dec 6.
PubMed 21135285Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014 Jan;65(1):124-37. doi: 10.1016/j.eururo.2013.09.046. Epub 2013 Oct 6.
PubMed 24207135Potosky AL, Davis WW, Hoffman RM, Stanford JL, Stephenson RA, Penson DF, Harlan LC. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst. 2004 Sep 15;96(18):1358-67. doi: 10.1093/jnci/djh259.
PubMed 15367568van Tol-Geerdink JJ, Leer JW, van Oort IM, van Lin EJ, Weijerman PC, Vergunst H, Witjes JA, Stalmeier PF. Quality of life after prostate cancer treatments in patients comparable at baseline. Br J Cancer. 2013 May 14;108(9):1784-9. doi: 10.1038/bjc.2013.181. Epub 2013 Apr 23.
PubMed 23612450Klotz L. Expectant management with selective delayed intervention for favorable risk prostate cancer. Urol Oncol. 2002 Sep-Oct;7(5):175-9. doi: 10.1016/s1078-1439(02)00183-7.
PubMed 12644212Reeve BB, Stover AM, Jensen RE, Chen RC, Taylor KL, Clauser SB, Collins SP, Potosky AL. Impact of diagnosis and treatment of clinically localized prostate cancer on health-related quality of life for older Americans: a population-based study. Cancer. 2012 Nov 15;118(22):5679-87. doi: 10.1002/cncr.27578. Epub 2012 Apr 27.
PubMed 22544633Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, Bjartell A, van der Schoot DK, Cornel EB, Conti GN, Boeve ER, Staerman F, Vis-Maters JJ, Vergunst H, Jaspars JJ, Strolin P, van Muilekom E, Schroder FH, Bangma CH, Roobol MJ. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol. 2013 Apr;63(4):597-603. doi: 10.1016/j.eururo.2012.11.005. Epub 2012 Nov 12.
PubMed 23159452Nguyen PL, D'Amico AV, Lee AK, Suh WW. Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer. 2007 Oct 1;110(7):1417-28. doi: 10.1002/cncr.22941.
PubMed 17694553Kuban DA, Thames HD, Levy LB, Horwitz EM, Kupelian PA, Martinez AA, Michalski JM, Pisansky TM, Sandler HM, Shipley WU, Zelefsky MJ, Zietman AL. Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):915-28. doi: 10.1016/s0360-3016(03)00632-1.
PubMed 14575822
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility and Safety of Transurethral HIFU in Various Prostate Diseases; Particularly Prostate Cancer
- ClinicalTrials.gov ID
- NCT03350529
- Acronym / sponsor ID
- HIFU-PRO / TO3/001/17
- Conditions
- Localised Prostate Cancer, Locally Advanced Prostate Cancer, Locally Recurrent Prostate Cancer, Benign Prostatic Hyperplasia
- Keywords
- prostate cancer, benign prostatic hyperplasia, benign prostatic obstruction, high intensity focused ultrasound, real-time temperature feedback control, magnetic resonance imaging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- University of Turku
- Study start
- 24 Jul 2017 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 31 May 2024 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Recently the major development of magnetic resonance imaging (MRI) has been achieved improving PC diagnosis and local staging. Even though PC is often multifocal, evidence indicates that both clinical outcome and prognosis of PC is determined predominantly by index lesion. Because of the notable risk of morbidities involving radical treatments and significant evolution of MRI, focal therapies have attained wide interest. One of the most interesting focal mini-invasive treatment is high intensity focused ultrasound (HIFU). HIFU technique exploits thermal energy; by raising target temperature over 55°C target volume is destroyed due to acute coagulation necrosis. Modern devices delivering HIFU to the prostate are transurethral and emit directional high intensity ultrasound to the focused regions utilising superior MRI guidance compared to older generation ultrasound guidance. Magnetic resonance thermometry technique utilizes noninvasive measurement of tissue temperature allowing monitoring real time temperature changes during treatment. The MRI treatment system is equipped with active dynamic temperature feedback control designed to maintain a constant temperature inside the target volume and at the boundary of the target area. By this way conformal three-dimensional ablative volumes with great spatial accuracy and precision can be achieved simultaneously avoiding damages to the surrounding sensitive tissues. Therapy verification is confirmed instantaneously after treatment by acquiring contrast enhanced MRI (CE-MRI) that visualise the non-perfused-volume (NPV) describing the success of total ablation of the target prostate volume.
This prospective clinical single center feasibility and safety study will evaluate the role of MRI guided transurethral HIFU ablation for various PD and clinical settings. All enrolled patients have prostate pathology and different clinical situation with need of definitive interventions and they are divided to four arms/groups according to specific inclusion criterion. Group 1 localised PC prior to RP, group 2 symptomatic locally advanced PC in need of palliative surgical intervention, group 3 locally recurrent PC after EBRT and group 4 symptomatic BPH in need for intervention.
The hypothesis is that MRI guided transurethral HIFU is feasible and safe in various prostate diseases and clinical settings. If hypothesis is proven for certain or for all groups, the investigators will continue with that group or groups to phase 2 clinical multi-institutional studies.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This study is an early phase 1 non-randomized prospective single-institutional and four arm study to determine the applicability, feasibility and safety of MRI guided transurethral HIFU ablation of prostate separately in each pre-specified group/arm (10 patients per group). Due to the encouraging feasibility and safety results, an amendment was made to the original study protocol to increase the amount of salvage group patients and BPH group patients. With the approval of the ethics committee, the sample size of the salvage group and BPH group was increased to a total of 40 patients and 30 patients, respectively.
| Arm | Type | Receives |
|---|---|---|
| Localised PC prior to RP | Experimental | Device: MRI guided transurethral HIFU ablation of prostatic tissueMRI 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. |
| Symptomatic locally advanced PC | Experimental | Device: MRI guided transurethral HIFU ablation of prostatic tissueMRI 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. |
| Locally recurrent PC after EBRT | Experimental | Device: MRI guided transurethral HIFU ablation of prostatic tissueMRI 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. |
| Symptomatic BPH | Experimental | Device: MRI guided transurethral HIFU ablation of prostatic tissueMRI 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). |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI guided transurethral HIFU ablation of prostatic tissueAlso: TULSA-PRO (Profound Medical Inc), Device: PAD-105The technology is developed to ablate targeted benign and malignant prostate tissue through transurethrally inserted probe that transmit ultrasound energy under MRI guidance and control. The therapeutic endpoint of this method is thermal coagulation of prostate tissue. | Device | Localised PC prior to RP, Locally recurrent PC after EBRT, Symptomatic BPH, Symptomatic locally advanced PC |
Primary outcome
Evaluate targeting accuracy of HIFU ablation separately in each study arm/group.
Time frame: 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.
Evaluate targeting accuracy volume of HIFU ablation separately in each study arm/group.
Time frame: 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.
Radiologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
Time frame: 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.
Histopathologically determined treatment accuracy of HIFU ablation in localised PC arm/group.
Time frame: 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.
Radiologically determined treatment accuracy of HIFU ablation in locally advanced PC arm/group.
Time frame: 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 locally recurrent PC after EBRT arm/group.
Time frame: 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.
Radiologically determined treatment accuracy of HIFU ablation in BPH arm/group.
Time frame: 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.
Safety of MRI guided transurethral HIFU ablation in various prostate diseases
Time frame: 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.
2 secondary outcomes
Preliminary efficacy of HIFU ablation to achieve sufficient tumour control in patients having local recurrent PC after EBRT
Time frame: 12 months from the treatment date
Image based follow up following HIFU ablation
Time frame: 12 months from the treatment date
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Background1.www.cancerregistry.fi
- Background: PubMed 25220842Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
- Background: PubMed 17030221Wasserman NF. Benign prostatic hyperplasia: a review and ultrasound classification. Radiol Clin North Am. 2006 Sep;44(5):689-710, viii. doi: 10.1016/j.rcl.2006.07.005.
- Background4. McDougal WS, Wein AJ, Kavoussi LR, et al: Campbell-Walsh Urology 10th Edition Review E-Book. A Saunders Title; 2011. p. 704
- Background: PubMed 6201879McNeal JE. Anatomy of the prostate and morphogenesis of BPH. Prog Clin Biol Res. 1984;145:27-53. No abstract available.
- Background: PubMed 16278465Cooperberg MR, Moul JW, Carroll PR. The changing face of prostate cancer. J Clin Oncol. 2005 Nov 10;23(32):8146-51. doi: 10.1200/JCO.2005.02.9751.
- Background: PubMed 21135285Bechis SK, Carroll PR, Cooperberg MR. Impact of age at diagnosis on prostate cancer treatment and survival. J Clin Oncol. 2011 Jan 10;29(2):235-41. doi: 10.1200/JCO.2010.30.2075. Epub 2010 Dec 6.
- Background: PubMed 24207135Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014 Jan;65(1):124-37. doi: 10.1016/j.eururo.2013.09.046. Epub 2013 Oct 6.
- Background: PubMed 15367568Potosky AL, Davis WW, Hoffman RM, Stanford JL, Stephenson RA, Penson DF, Harlan LC. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst. 2004 Sep 15;96(18):1358-67. doi: 10.1093/jnci/djh259.
- Background: PubMed 23612450van Tol-Geerdink JJ, Leer JW, van Oort IM, van Lin EJ, Weijerman PC, Vergunst H, Witjes JA, Stalmeier PF. Quality of life after prostate cancer treatments in patients comparable at baseline. Br J Cancer. 2013 May 14;108(9):1784-9. doi: 10.1038/bjc.2013.181. Epub 2013 Apr 23.
- Background: PubMed 12644212Klotz L. Expectant management with selective delayed intervention for favorable risk prostate cancer. Urol Oncol. 2002 Sep-Oct;7(5):175-9. doi: 10.1016/s1078-1439(02)00183-7.
- Background: PubMed 22544633Reeve BB, Stover AM, Jensen RE, Chen RC, Taylor KL, Clauser SB, Collins SP, Potosky AL. Impact of diagnosis and treatment of clinically localized prostate cancer on health-related quality of life for older Americans: a population-based study. Cancer. 2012 Nov 15;118(22):5679-87. doi: 10.1002/cncr.27578. Epub 2012 Apr 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Boström, M.D.Ph.D principal investigator
Department of Urology, VSSHP, University of Turku
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI guided transurethral HIFU ablation of prostatic tissue in people with Localised Prostate Cancer and Locally Advanced Prostate Cancer, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate targeting accuracy of HIFU ablation separately in each study arm/group. (time frame: The date of HIFU treatment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03350529, which also lists 48 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.