Back to resultsNeoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer (NeoADT-TULSA)
Primary Purpose
Localized Prostate Carcinoma, Castration-Naive Prostate Cancer, Intermediate Risk Prostate Cancer
Status
Not yet recruiting
Phase
Phase 1
Locations
Finland
Study Type
Interventional
Intervention
Degarelix
MRI-guided transurethral ultrasound ablation (TULSA)
Sponsored by
About this trial
This is an interventional treatment trial for Localized Prostate Carcinoma focused on measuring MRI-guided transurethral ultrasound ablation, Androgen deprivation therapy, Neoadjuvant androgen deprivation therapy, TULSA, Prostate cancer, Thermal ablation, Therapeutic ultrasound, Ablation therapy
Eligibility Criteria
Inclusion Criteria: Male age ≥ 40 years and candidate for radical prostate cancer treatment Estimated life expectancy > 8 years At least one MRI-visible and biopsy-concordant tumor defined as Prostate Imaging-Reporting and Data System v2 (PI-RADS v2.1) ≥ 3 Biopsy-confirmed, intermediate-risk localized prostate cancer: Clinical or radiological tumor stage ≤ T2c, N0, M0 ISUP GG 2 or 3 Biopsy obtained ≥ 6 weeks and ≤ 12 months before treatment PSA ≤ 20 ng/ml No prior definitive treatment of prostate cancer Eligible for MRI Eligible for general anesthesia (American Society of Anesthesiologists Class III or less) Patients taking 5-alpha reductase inhibitors (5-ARIs) are eligible if use is discontinued three months before and throughout the study period. Informed consent: The patient must speak Finnish, English, or Swedish and must be able to understand the meaning of the study. The patient must be willing and able to sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff. Exclusion Criteria: Prior prostate cancer treatment with chemotherapy or hormonal therapy, including chemical or surgical castration, antiandrogen therapy, or androgen-receptor signaling inhibitors. Relative or absolute contraindication to Degarelix Severe, active cardiovascular comorbidity including unstable angina pectoris, congestive heart failure, deep vein thrombosis, pulmonary embolism, or myocardial infarction within the last six months. Inability to undergo MRI due to claustrophobia or contraindications (cardiac pacemaker, intracranial clips, etc.) Severe kidney failure as determined by estimated glomerular filtration rate (eGFR) less than 30 ml/min per 1.73 m2 Prostate calcifications obstructing the planned ultrasound beam path in the line of sight of the MRI visible tumor Prostate cysts at the prostate capsule within the planned ultrasound beam path in the line of sight of the MRI visible tumor Evidence of extraprostatic disease based on imaging (MRI, bone scintigraphy, single-photon emission tomography, computed tomography, prostate-specific membrane antigen-positron emission tomography [PSMA-PET]) or histopathology History of chronic inflammatory conditions (e.g., inflammatory bowel disease) affecting the rectum (also includes rectal fistula and anal/rectal stenosis) Hip replacement surgery or other metal in the pelvic area Known allergy or contraindication to gadolinium or gastro-intestinal anti-spasmodic drug glucagon Concomitant treatment with medications contraindicated to Glucagen used as antispasmolytic agent during TULSA treatment (e.g., Feochromocytoma) Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist Another primary malignancy unless disease-free survival is > 8 years
Sites / Locations
- Turku University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation
Arm Description
After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.
Outcomes
Primary Outcome Measures
Change in prostate volume after neoadjuvant ADT
The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Change in prostate tumor volume after neoadjuvant ADT
The prostate tumor volume change will be determined by comparing the prostate tumor volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
The frequency and severity of adverse events
The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined by using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.
Secondary Outcome Measures
Change in prostate tumor-capsule contact length after neoadjuvant ADT
The prostate tumor-capsule contact length change will be determined by comparing the prostate tumor-capsule contact length measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Change in prostate vascular perfusion after neoadjuvant ADT
The change in prostate vascular perfusion will be determined by comparing average blood flow values in the prostate measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Change in prostate tumor vascular perfusion after neoadjuvant ADT
The change in prostate tumor vascular perfusion will be determined by comparing average blood flow values in the prostate tumor measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Change in periprostatic, prostate and tumor tissue structures after neoadjuvant ADT
The change in periprostatic, prostate and tumor tissue structures will be determined by comparing the radiomics features extracted from T2-weighted, T2 relaxation time mapping, and diffusion-weighted images at four, eight, and 12 weeks of ADT to that at baseline.
Thermal coverage after whole-prostate gland TULSA
Thermal coverage of the target volume achieved by whole-prostate gland TULSA will be determined by comparing physician-defined target boundaries to MRI measurements of temperature distributions, thermal dose distributions, and acute treatment-induced perfusion defect immediately post-treatment.
Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT
The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite-26 (EPIC-26) questionnaire at 12 weeks of ADT to that at baseline. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.
Change in lower urinary tract symptoms after neoadjuvant ADT
The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at 12 weeks of ADT to that at baseline. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.
Change in erectile function after neoadjuvant ADT
The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at 12 weeks of ADT to that at baseline. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.
Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT and whole-prostate gland TULSA
The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite (EPIC-26) questionnaire at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.
Change in lower urinary tract symptoms after neoadjuvant ADT and whole-prostate gland TULSA
The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.
Change in erectile function after neoadjuvant ADT and whole-prostate gland TULSA
The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.
The frequency and severity of adverse events during extended follow-up
The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.
Salvage therapy-free survival
Salvage therapy-free survival will be defined as freedom from radical salvage treatments for prostate cancer including radical prostatectomy, radiotherapy, or ablation, and reported as the proportion of subjects who have not reached those events.
Systemic therapy-free survival
Systemic therapy-free survival will be defined as freedom from additional systemic therapy including but not limited to additional ADT or chemotherapy for the treatment of prostate cancer, and reported as the proportion of subjects who have not reached those events.
Failure-free survival
Failure-free survival will be defined as freedom from salvage treatment, systemic treatment, metastases, or death from prostate cancer, and reported as the proportion of subjects who have not reached those events.
Metastasis-free, prostate cancer-specific, and overall survival
Metastasis-free, prostate cancer-specific and overall survivals will be assessed one, three, and five years after TULSA and reported as the proportion of subjects who have not reached those endpoints.
Biochemical failure-free survival
PSA at each timepoint, as well as PSA nadir, will be reported. The proportion of subjects with biochemical failure, defined as a PSA value more than 2.0 ng/ml above nadir, will be reported.
Freedom from biopsy-proven clinically-significant prostate cancer
Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The proportion of subjects with a clinically-significant disease, defined as Gleason grade ≥ 3 + 4 and ISUP (International Society of Urological Pathology) grade group ≥ 2 prostate cancer, on biopsy, will be reported.
Freedom from any biopsy-proven prostate cancer
Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The number, location, grade, and percent of cancer involvement within each core will be collected. The proportion of subjects with any prostate cancer on biopsy, will be reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05917860
Brief Title
Neoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer
Acronym
NeoADT-TULSA
Official Title
Effect of Neoadjuvant Degarelix on MRI-guided Transurethral Ultrasound Ablation (TULSA) in Patients With Intermediate-risk Prostate Cancer: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
December 31, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Turku University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Clinical studies have shown that magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate is safe and effective. In the TULSA procedure, prostate tissue is killed by heating with ultrasound. This clinical trial explores if adding drug therapy with Degarelix before TULSA has the potential to improve further the effectiveness of TULSA in the treatment of localized prostate cancer, especially for patients with more aggressive diseases.
Detailed Description
Androgen deprivation therapy (ADT) has been shown to reduce prostate and tumor size. In this study, magnetic resonance imaging (MRI) is used to investigate the effect of Degarelix ADT on the properties of prostate tissue that can affect the heating of the tissues in the TULSA procedure. The main goal is to find out if ADT can change the tissue structure in a way that improves the ability of the TULSA procedure to heat tissues and better kill the diseased tissue, reducing the chance of the disease reoccurring. ADT and the TULSA procedure can help patients with more aggressive diseases avoid the adverse effects associated with surgery or radiation therapy. Specific objectives are:
To measure the change in prostate and tumor size, tissue structural changes, and the blood flow within the prostate after ADT.
To measure the distribution of heating over the prostate after TULSA treatment.
To evaluate complications and genitourinary function and quality of life with patient-reported outcome measures.
To evaluate local cancer control and longer-term oncological outcomes after combination therapy of neoadjuvant ADT and TULSA treatment.
About 15 subjects will participate. Each will receive Degarelix for three months, followed by whole-prostate gland TULSA treatment, and be followed for five years. Throughout the study, subjects will receive MRI scans and complete questionnaires regarding functional status and quality of life to understand the side effects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Localized Prostate Carcinoma, Castration-Naive Prostate Cancer, Intermediate Risk Prostate Cancer, Prostate Cancer
Keywords
MRI-guided transurethral ultrasound ablation, Androgen deprivation therapy, Neoadjuvant androgen deprivation therapy, TULSA, Prostate cancer, Thermal ablation, Therapeutic ultrasound, Ablation therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Procedure: Magnetic resonance imaging-guided transurethral ultrasound ablation of the prostate (TULSA)
Drug: Degarelix
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation
Arm Type
Experimental
Arm Description
After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.
Intervention Type
Drug
Intervention Name(s)
Degarelix
Other Intervention Name(s)
Firmagon
Intervention Description
Degarelix is injected subcutaneously into the fatty tissue of the abdomen. A typical protocol consists of a starting dose of 240 mg with a maintenance dose of 80 mg administered every 28 days. In this study, one starting dose and two maintenance doses of Degarelix will be administered between baseline and TULSA treatment in accordance with the terms of Degarelix marketing authorizations.
Intervention Type
Device
Intervention Name(s)
MRI-guided transurethral ultrasound ablation (TULSA)
Other Intervention Name(s)
TULSA-PRO
Intervention Description
MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) will be used to deliver whole-prostate gland treatment in accordance with the terms of TULSA marketing authorizations. The treating physicians will contour the entire prostate gland for a whole gland ablation.
Primary Outcome Measure Information:
Title
Change in prostate volume after neoadjuvant ADT
Description
The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
Change in prostate tumor volume after neoadjuvant ADT
Description
The prostate tumor volume change will be determined by comparing the prostate tumor volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
The frequency and severity of adverse events
Description
The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined by using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.
Time Frame
Every follow-up visit until the first year of follow-up.
Secondary Outcome Measure Information:
Title
Change in prostate tumor-capsule contact length after neoadjuvant ADT
Description
The prostate tumor-capsule contact length change will be determined by comparing the prostate tumor-capsule contact length measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
Change in prostate vascular perfusion after neoadjuvant ADT
Description
The change in prostate vascular perfusion will be determined by comparing average blood flow values in the prostate measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
Change in prostate tumor vascular perfusion after neoadjuvant ADT
Description
The change in prostate tumor vascular perfusion will be determined by comparing average blood flow values in the prostate tumor measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
Change in periprostatic, prostate and tumor tissue structures after neoadjuvant ADT
Description
The change in periprostatic, prostate and tumor tissue structures will be determined by comparing the radiomics features extracted from T2-weighted, T2 relaxation time mapping, and diffusion-weighted images at four, eight, and 12 weeks of ADT to that at baseline.
Time Frame
Baseline and four, eight, and 12 weeks of ADT.
Title
Thermal coverage after whole-prostate gland TULSA
Description
Thermal coverage of the target volume achieved by whole-prostate gland TULSA will be determined by comparing physician-defined target boundaries to MRI measurements of temperature distributions, thermal dose distributions, and acute treatment-induced perfusion defect immediately post-treatment.
Time Frame
Immediately after the TULSA procedure.
Title
Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT
Description
The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite-26 (EPIC-26) questionnaire at 12 weeks of ADT to that at baseline. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.
Time Frame
Baseline and 12 weeks of ADT.
Title
Change in lower urinary tract symptoms after neoadjuvant ADT
Description
The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at 12 weeks of ADT to that at baseline. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.
Time Frame
Baseline and 12 weeks of ADT.
Title
Change in erectile function after neoadjuvant ADT
Description
The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at 12 weeks of ADT to that at baseline. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.
Time Frame
Baseline and 12 weeks of ADT.
Title
Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT and whole-prostate gland TULSA
Description
The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite (EPIC-26) questionnaire at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.
Time Frame
Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
Title
Change in lower urinary tract symptoms after neoadjuvant ADT and whole-prostate gland TULSA
Description
The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.
Time Frame
Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
Title
Change in erectile function after neoadjuvant ADT and whole-prostate gland TULSA
Description
The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.
Time Frame
Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
Title
The frequency and severity of adverse events during extended follow-up
Description
The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.
Time Frame
Every follow-up visit until the five years of follow-up.
Title
Salvage therapy-free survival
Description
Salvage therapy-free survival will be defined as freedom from radical salvage treatments for prostate cancer including radical prostatectomy, radiotherapy, or ablation, and reported as the proportion of subjects who have not reached those events.
Time Frame
Every post-TULSA follow-up visit until the five years of follow-up.
Title
Systemic therapy-free survival
Description
Systemic therapy-free survival will be defined as freedom from additional systemic therapy including but not limited to additional ADT or chemotherapy for the treatment of prostate cancer, and reported as the proportion of subjects who have not reached those events.
Time Frame
Every post-TULSA follow-up visit until the five years of follow-up.
Title
Failure-free survival
Description
Failure-free survival will be defined as freedom from salvage treatment, systemic treatment, metastases, or death from prostate cancer, and reported as the proportion of subjects who have not reached those events.
Time Frame
Every post-TULSA follow-up visit until the five years of follow-up.
Title
Metastasis-free, prostate cancer-specific, and overall survival
Description
Metastasis-free, prostate cancer-specific and overall survivals will be assessed one, three, and five years after TULSA and reported as the proportion of subjects who have not reached those endpoints.
Time Frame
One, three and five years after the TULSA procedure.
Title
Biochemical failure-free survival
Description
PSA at each timepoint, as well as PSA nadir, will be reported. The proportion of subjects with biochemical failure, defined as a PSA value more than 2.0 ng/ml above nadir, will be reported.
Time Frame
One, three, and five years after the TULSA procedure.
Title
Freedom from biopsy-proven clinically-significant prostate cancer
Description
Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The proportion of subjects with a clinically-significant disease, defined as Gleason grade ≥ 3 + 4 and ISUP (International Society of Urological Pathology) grade group ≥ 2 prostate cancer, on biopsy, will be reported.
Time Frame
Twelve months after the TULSA procedure
Title
Freedom from any biopsy-proven prostate cancer
Description
Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The number, location, grade, and percent of cancer involvement within each core will be collected. The proportion of subjects with any prostate cancer on biopsy, will be reported.
Time Frame
Twelve months after the TULSA procedure
Other Pre-specified Outcome Measures:
Title
Change in prostate volume after whole-prostate gland TULSA
Description
The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at three, and 12 months after TULSA to that at TULSA procedure.
Time Frame
Three and twelve months after TULSA procedure
Title
Change in maximum urinary flow rate after neoadjuvant ADT and whole-gland TULSA
Description
The change in maximum urinary flow rate (Qmax) (ml/s) will be determined by comparing Qmax values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.
Time Frame
Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
Title
Change in average urinary flow rate after neoadjuvant ADT and whole-gland TULSA
Description
The change in average urinary flow rate (ml/s) will be determined by comparing average flow rate values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.
Time Frame
Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
Title
Change in post-void residual volume after neoadjuvant ADT and whole-gland TULSA
Description
The change in post-void residual volume (PVR) (ml) will be determined by comparing PVR values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.
Time Frame
Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
Title
Change in voided volume after neoadjuvant ADT and whole-gland TULSA
Description
The change in voided volume (ml) will be determined by comparing voided volume values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.
Time Frame
Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
Title
Freedom from any suspicious lesion on MRI
Description
3T prostate multiparametric MRI three and twelve months after TULSA treatment will be assessed for residual or recurrent disease according to the Prostate Imaging for Recurrence Reporting (PI-RR) system guidelines. The proportion of subjects with a suspicious lesion on MRI, defined as lesion ≥ PI-RR 3, will be reported.
Time Frame
Three and twelve months after the TULSA procedure
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male age ≥ 40 years and candidate for radical prostate cancer treatment
Estimated life expectancy > 8 years
At least one MRI-visible and biopsy-concordant tumor defined as Prostate Imaging-Reporting and Data System v2 (PI-RADS v2.1) ≥ 3
Biopsy-confirmed, intermediate-risk localized prostate cancer:
Clinical or radiological tumor stage ≤ T2c, N0, M0
ISUP GG 2 or 3
Biopsy obtained ≥ 6 weeks and ≤ 12 months before treatment
PSA ≤ 20 ng/ml
No prior definitive treatment of prostate cancer
Eligible for MRI
Eligible for general anesthesia (American Society of Anesthesiologists Class III or less)
Patients taking 5-alpha reductase inhibitors (5-ARIs) are eligible if use is discontinued three months before and throughout the study period.
Informed consent: The patient must speak Finnish, English, or Swedish and must be able to understand the meaning of the study. The patient must be willing and able to sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff.
Exclusion Criteria:
Prior prostate cancer treatment with chemotherapy or hormonal therapy, including chemical or surgical castration, antiandrogen therapy, or androgen-receptor signaling inhibitors.
Relative or absolute contraindication to Degarelix
Severe, active cardiovascular comorbidity including unstable angina pectoris, congestive heart failure, deep vein thrombosis, pulmonary embolism, or myocardial infarction within the last six months.
Inability to undergo MRI due to claustrophobia or contraindications (cardiac pacemaker, intracranial clips, etc.)
Severe kidney failure as determined by estimated glomerular filtration rate (eGFR) less than 30 ml/min per 1.73 m2
Prostate calcifications obstructing the planned ultrasound beam path in the line of sight of the MRI visible tumor
Prostate cysts at the prostate capsule within the planned ultrasound beam path in the line of sight of the MRI visible tumor
Evidence of extraprostatic disease based on imaging (MRI, bone scintigraphy, single-photon emission tomography, computed tomography, prostate-specific membrane antigen-positron emission tomography [PSMA-PET]) or histopathology
History of chronic inflammatory conditions (e.g., inflammatory bowel disease) affecting the rectum (also includes rectal fistula and anal/rectal stenosis)
Hip replacement surgery or other metal in the pelvic area
Known allergy or contraindication to gadolinium or gastro-intestinal anti-spasmodic drug glucagon
Concomitant treatment with medications contraindicated to Glucagen used as antispasmolytic agent during TULSA treatment (e.g., Feochromocytoma)
Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist
Another primary malignancy unless disease-free survival is > 8 years
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mikael HJ Anttinen, MD, PhD
Phone
+358-2-3133650
Email
mikael.anttinen@tyks.fi
First Name & Middle Initial & Last Name or Official Title & Degree
Kaisa Reunanen
Email
kaisa.reunanen@tyks.fi
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikael HJ Anttinen, MD, PhD
Organizational Affiliation
Department of Urology, University of Turku and Turku University Hospital, Turku, Finland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Turku University Hospital
City
Turku
State/Province
Southwest Finland
ZIP/Postal Code
20521
Country
Finland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mikael HJ Anttinen, MD, PhD
Phone
+358-2-3133650
Email
mikael.anttinen@tyks.fi
First Name & Middle Initial & Last Name & Degree
Kaisa Reunanen
Email
kaisa.reunanen@tyks.fi
12. IPD Sharing Statement
Citations:
PubMed Identifier
36465377
Citation
Anttinen M, Blanco Sequeiros R, Bostrom PJ, Taimen P. Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques. Front Oncol. 2022 Nov 17;12:1043688. doi: 10.3389/fonc.2022.1043688. eCollection 2022.
Results Reference
background
PubMed Identifier
27595377
Citation
Valerio M, Cerantola Y, Eggener SE, Lepor H, Polascik TJ, Villers A, Emberton M. New and Established Technology in Focal Ablation of the Prostate: A Systematic Review. Eur Urol. 2017 Jan;71(1):17-34. doi: 10.1016/j.eururo.2016.08.044. Epub 2016 Aug 29.
Results Reference
background
PubMed Identifier
33021440
Citation
Klotz L, Pavlovich CP, Chin J, Hatiboglu G, Koch M, Penson D, Raman S, Oto A, Futterer J, Serrallach M, Relle J, Lotan Y, Heidenreich A, Bonekamp D, Haider M, Tirkes T, Arora S, Macura KJ, Costa DN, Persigehl T, Pantuck AJ, Bomers J, Burtnyk M, Staruch R, Eggener S. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer. J Urol. 2021 Mar;205(3):769-779. doi: 10.1097/JU.0000000000001362. Epub 2020 Oct 6.
Results Reference
background
Citation
EAU Guidelines 2023, presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-16-5.
Results Reference
background
PubMed Identifier
21440505
Citation
Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011 May;12(5):451-9. doi: 10.1016/S1470-2045(11)70063-8.
Results Reference
background
PubMed Identifier
25884478
Citation
Hu J, Xu H, Zhu W, Wu F, Wang J, Ding Q, Jiang H. Neo-adjuvant hormone therapy for non-metastatic prostate cancer: a systematic review and meta-analysis of 5,194 patients. World J Surg Oncol. 2015 Feb 22;13:73. doi: 10.1186/s12957-015-0503-z.
Results Reference
background
PubMed Identifier
23769268
Citation
Nishiyama T. Serum testosterone levels after medical or surgical androgen deprivation: a comprehensive review of the literature. Urol Oncol. 2014 Jan;32(1):38.e17-28. doi: 10.1016/j.urolonc.2013.03.007. Epub 2013 Jun 13.
Results Reference
background
PubMed Identifier
34084124
Citation
Christie DRH, Mitina N, Sharpley CF. A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy. Curr Urol. 2021 Mar;15(1):63-67. doi: 10.1097/CU9.0000000000000008. Epub 2021 Mar 29.
Results Reference
background
PubMed Identifier
12913699
Citation
Klotz LH, Goldenberg SL, Jewett MA, Fradet Y, Nam R, Barkin J, Chin J, Chatterjee S; Canadian Uro-Oncology Group. Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol. 2003 Sep;170(3):791-4. doi: 10.1097/01.ju.0000081404.98273.fd.
Results Reference
background
PubMed Identifier
17054269
Citation
Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD006019. doi: 10.1002/14651858.CD006019.pub2.
Results Reference
background
PubMed Identifier
18355899
Citation
Sumitomo M, Hayashi M, Watanabe T, Tsugawa M, Noma H, Yamaguchi A, Nagakura K, Hayakawa M, Uchida T. Efficacy of short-term androgen deprivation with high-intensity focused ultrasound in the treatment of prostate cancer in Japan. Urology. 2008 Dec;72(6):1335-40. doi: 10.1016/j.urology.2007.12.041. Epub 2008 Mar 20.
Results Reference
background
Citation
Aoyagi, Teiichiro, and Isao Kuroda. Enhancement of HIFU Effect by Simultaneous Short Course Degarelix for Early Stage Prostate Cancer: A Pilot Study. Open Journal of Urology 6.03 (2016): 49-54.
Results Reference
background
PubMed Identifier
24661333
Citation
Crawford ED, Shore ND, Moul JW, Tombal B, Schroder FH, Miller K, Boccon-Gibod L, Malmberg A, Olesen TK, Persson BE, Klotz L. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology. 2014 May;83(5):1122-8. doi: 10.1016/j.urology.2014.01.013. Epub 2014 Mar 22.
Results Reference
background
PubMed Identifier
34337481
Citation
Anttinen M, Makela P, Viitala A, Nurminen P, Suomi V, Sainio T, Saunavaara J, Taimen P, Sequeiros RB, Bostrom PJ. Salvage Magnetic Resonance Imaging-guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer: 12-Month Functional and Oncological Results. Eur Urol Open Sci. 2020 Nov 25;22:79-87. doi: 10.1016/j.euros.2020.10.007. eCollection 2020 Dec.
Results Reference
background
PubMed Identifier
32897169
Citation
Anttinen M, Makela P, Nurminen P, Yli-Pietila E, Suomi V, Sainio T, Saunavaara J, Taimen P, Blanco Sequeiros R, Bostrom PJ. Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer. Scand J Urol. 2020 Dec;54(6):481-486. doi: 10.1080/21681805.2020.1814857. Epub 2020 Sep 8.
Results Reference
background
PubMed Identifier
35029127
Citation
Dora C, Clarke GM, Frey G, Sella D. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer: A Systematic Review. J Endourol. 2022 Jun;36(6):841-854. doi: 10.1089/end.2021.0866. Epub 2022 Mar 7.
Results Reference
background
PubMed Identifier
33026934
Citation
Pooli A, Johnson DC, Shirk J, Markovic D, Sadun TY, Sisk AE Jr, Mohammadian Bajgiran A, Afshari Mirak S, Felker ER, Hughes AK, Raman SS, Reiter RE. Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings. J Urol. 2021 Feb;205(2):444-451. doi: 10.1097/JU.0000000000001389. Epub 2020 Oct 7.
Results Reference
background
PubMed Identifier
33898790
Citation
Bjoreland U, Nyholm T, Jonsson J, Skorpil M, Blomqvist L, Strandberg S, Riklund K, Beckman L, Thellenberg-Karlsson C. Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy. Phys Imaging Radiat Oncol. 2021 Feb 24;17:117-123. doi: 10.1016/j.phro.2021.01.004. eCollection 2021 Jan.
Results Reference
background
PubMed Identifier
27943566
Citation
Washino S, Hirai M, Saito K, Kobayashi Y, Arai Y, Miyagawa T. Impact of Androgen Deprivation Therapy on Volume Reduction and Lower Urinary Tract Symptoms in Patients with Prostate Cancer. Low Urin Tract Symptoms. 2018 Jan;10(1):57-63. doi: 10.1111/luts.12142. Epub 2016 Dec 12.
Results Reference
background
PubMed Identifier
25820537
Citation
Hotker AM, Mazaheri Y, Zheng J, Moskowitz CS, Berkowitz J, Lantos JE, Pei X, Zelefsky MJ, Hricak H, Akin O. Prostate Cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI. Eur Radiol. 2015 Sep;25(9):2665-72. doi: 10.1007/s00330-015-3688-1. Epub 2015 Mar 29.
Results Reference
background
PubMed Identifier
31508924
Citation
Marra G, Dell'oglio P, Baghdadi M, Cathelineau X, Sanchez-Salas R; EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control (ENHANCE) Study. Multimodal treatment in focal therapy for localized prostate cancer using concomitant short-term androgen deprivation therapy: the ENHANCE prospective pilot study. Minerva Urol Nefrol. 2019 Oct;71(5):544-548. doi: 10.23736/S0393-2249.19.03599-9. Epub 2019 Sep 6.
Results Reference
background
Links:
URL
http://hifu.utu.fi
Description
Turku HIFU research centre
Learn more about this trial
Neoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer
We'll reach out to this number within 24 hrs