Potency pReservation In Prostate cAncer Patients Treated With UltraSound-guided Low-dose Rate Brachytherapy

Study Overview
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Brief Summary
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The purpose of this study is to develop and evaluate a Magnetic Resonance (MR) fusion 3D Ultrasound (US) guided Low dose rate (LDR) brachytherapy technique that significantly spares prostatic neurovascular bundles (a bundle of nerves and vessels that run beside the prostate) and penile bulb (base of the penis), while still trying to effectively treat the prostate cancer.

Detailed Description
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Low dose rate (LDR) brachytherapy is an excellent treatment strategy for patients with prostate confined cancers, achieving high curative rates. However, LDR brachytherapy has been linked with long-term erectile dysfunction (ED), with a broad range of reported incidence in the literature. The pathophysiology associated with ED is complex and variable among different prostate cancer treatment strategies. In the post radical prostatectomy (RP) setting, ED is usually an immediate phenomenon and associated with neuropraxia caused by trauma and inflammation (Nandipati 2006). On the contrary, external beam radiotherapy (EBRT) related ED frequently occurs between 6-24 months and is believed to be vasculogenic in nature and caused by veno-vascular luminal occlusion (Mulhall et al. 2005) that culminates into fibrosis of the corporal tissue. In the post brachytherapy setting, seems plausible that a combination of both nerve and vascular damage are involved in the ED pathogenesis as erectile scores seem to reduce in the first months post implant (likely due to trauma) followed by a subsequent recovery and then, a gradual decline (Mabjeesh 2005). Despite a more complex pathophysiology, rates of ED post LDR brachytherapy seem to be lower than post EBRT or RP treatment (Crook 2010, Putora 2015). This may be associated with a significantly lower degree of trauma to the surrounding healthy tissue compared with trauma caused by RP and a more conformal dose around the prostate when contrasted with EBRT. In this regard, brachytherapy delivers a lesser dose to important structures previously correlated with an erectile function such as the internal pudendal artery (IPA), penile bulb, corpus cavernosum and possibly the neurovascular bundle. Currently, some strategies have been developed in an attempt to minimize ED post radiotherapy. In the POTEN-C clinical trial (NCT03525262), 120 patients are being randomized to stereotactic ablative radiotherapy with or without neurovascular sparing (neurovascular bundle, IPA and penile bulb/corpus carvenosum) with ED as the primary endpoint. Although the concept is intriguing, LDR brachytherapy has superior dose conformality and hence, a better chance to reduce radiation dose to the surrounding structures involved in the erectile function while still effectively treating the prostate cancer.

Official Title
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Potency pReservation In Prostate cAncer Patients Treated With UltraSound-guided Low-dose Rate Brachytherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Low dose rate (LDR) brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-confirmed adenocarcinoma of the prostate NCCN-defined low- or favourable intermediate-risk prostate cancer patients All pathological cores confined to one lobe of the prostate (minimum of 12 cores sampled), unless a recent multiparametric prostate MR-scan (mpMR) (with < 6 months from the enrollment date) indicates a dominant intra-prostatic lesion (DIL) located at the prostatic lobe where a higher number of cores and Gleason score was found positive. PIRADS v2 score 3-5 lesions are considered DILs. No or mild erectile function impairment (score ≥18 in International Index of Erectile Function- 5 [IIEF-5] without PDE-5 inhibitor assistance) Sexually active No contraindications to prostate LDR brachytherapy Exclusion Criteria: Core positivity in both lobes of the prostate with no DIL detected on mpMR mpMR suggesting presence of DILs in both lobes of the prostate Contraindications to receiving a MR-scan Medically unfit for general and/or spinal anesthesia IPSS score > 15 Inflammatory bowel disease Prior abdominal-perineal resection Presence of distant metastases and/or nodal disease Older than 75 years of age Use of cytoreductive prostate treatment (including 5 alpha-reductase inhibitors) NCCN-defined unfavourable intermediate or high-risk prostate cancer Signs of extra-capsular extension or seminal vesicle involvement on MR-scan Prior TURP > 3mm of median lobe protrusion to bladder measured in mpMR (Roeloffzen 2011) Prior RT to the pelvis Significant artifact on MR-Scan (e.g. caused by hip prosthesis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, single-arm clinical trial to enroll a total of 10 low- or favourable intermediate-risk prostate cancer patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prostate Cancer Patients<br>Low- or favourable intermediate-risk prostate cancer patients | Radiation: Low dose rate (LDR) brachytherapy<br>* Low dose rate (LDR) brachytherapy is a type of radiation treatment where doctor places the radioactive implants (seeds) inside patient's prostate gland and these seeds emits low dose radiation over a certain period of time. During low-dose-rate brachytherapy, a continuous low dose of radiation is released over time -from several hours to several days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients receiving this experimental brachytherapy technique and achieving acceptable dose distribution at 1-month post-implant. | Acceptable dose distribution is defined as: Target volume (Prostate, excluding a 5 mm expansion of the Neurovascular bundle) D90 ≥ 140 Gy Contralateral neurovascular bundle median dose ≤ 50 Gy Prostatic bulb D10 dose ≤ 50 Gy (Chasseray 2019) Urethra D30 < 130% of the prescription dose | 1 month after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient with preserved erectile function Erectile Function (IIEF) >= 18) | The IIEF classifies the severity of ED into five categories stratified by score No ED.26-30 Mild.22-25 Mild to moderate.17-21 Moderate.11-16 Severe.6-10 | 1, 6, 12, 18, 24, 36, 48, 60 months post intervention | 
| Post-procedure PSA dynamic | PSA curve post procedure | 6, 12, 18, 24, 36, 48, 60 months post intervention | 
| Acute and long-term GU and GI toxicity | Evaluate acute and long-term G3 or larger toxicity based on NCI-CTCAE 5.0 score system. Grade 1 to Grade 5. Higher the grade more severe is the toxicity. | 1, 6, 12, 18, 24, 36, 48, 60 months post intervention | 
| Biochemical failure | Biochemical failure will be assessed according to the Phoenix criteria (nadir + 2.0ng/mL) | 1, 6, 12, 18, 24, 36, 48, 60 months post intervention | 
| Local recurrence | To assess the rate of biopsy-proven local recurrence | Until study completion with 5 years of follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brachytherapy, Radiation, Low Dose Rate