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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.

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.

Degarelix

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.

MRI-guided transurethral ultrasound ablation (TULSA)

Mikael HJ Anttinen, MD, PhD

Kaisa Reunanen

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.

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:

1. To measure the change in prostate and tumor size, tissue structural changes, and the blood flow within the prostate after ADT.
2. To measure the distribution of heating over the prostate after TULSA treatment.
3. To evaluate complications and genitourinary function and quality of life with patient-reported outcome measures.
4. 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.

Procedure: Magnetic resonance imaging-guided transurethral ultrasound ablation of the prostate (TULSA)

Drug: Degarelix

Neoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer

Effect of Neoadjuvant Degarelix on MRI-guided Transurethral Ultrasound Ablation (TULSA) in Patients With Intermediate-risk Prostate Cancer: A Pilot Study

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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 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 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 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 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 survivals will be assessed one, three, and five years after TULSA and reported as the proportion of subjects who have not reached those endpoints.

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.

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.

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.

Spots Global Cancer Trial Database for neoadjuvant androgen deprivation therapy