Clinical trial NCT04718987: Potency pReservation In Prostate cAncer Patients Treated With UltraSound-guided Low-dose Rate Brachytherapy
Official title: Potency pReservation In Prostate cAncer Patients Treated With UltraSound-guided Low-dose Rate Brachytherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: Brachytherapy
Radiation
Low Dose Rate
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2021-01-22
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, single-arm clinical trial to enroll a total of 10 low- or favourable intermediate-risk prostate cancer patients.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Rate of patients receiving this experimental brachytherapy technique and achieving acceptable dose distribution at 1-month post-implant.
timeFrame: 1 month after intervention
Secondary outcomes:
measure: Number of patient with preserved erectile function Erectile Function (IIEF) >= 18)
timeFrame: 1, 6, 12, 18, 24, 36, 48, 60 months post intervention
measure: Post-procedure PSA dynamic
timeFrame: 6, 12, 18, 24, 36, 48, 60 months post intervention
measure: Acute and long-term GU and GI toxicity
timeFrame: 1, 6, 12, 18, 24, 36, 48, 60 months post intervention
measure: Biochemical failure
timeFrame: 1, 6, 12, 18, 24, 36, 48, 60 months post intervention
measure: Local recurrence
timeFrame: Until study completion with 5 years of follow up
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
Study officials:
affiliation: London Health Sciences Centre- London Regional Cancer Program
name: Lucas Mendez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mulhall J, Ahmed A, Parker M, Mohideen N. The hemodynamics of erectile dysfunction following external beam radiation for prostate cancer. J Sex Med. 2005 May;2(3):432-7. doi: 10.1111/j.1743-6109.2005.20362.x.
citation: Mabjeesh N, Chen J, Beri A, Stenger A, Matzkin H. Sexual function after permanent 125I-brachytherapy for prostate cancer. Int J Impot Res. 2005 Jan-Feb;17(1):96-101. doi: 10.1038/sj.ijir.3901271.
citation: Putora PM, Engeler D, Haile SR, Graf N, Buchauer K, Schmid HP, Plasswilm L. Erectile function following brachytherapy, external beam radiotherapy, or radical prostatectomy in prostate cancer patients. Strahlenther Onkol. 2016 Mar;192(3):182-9. doi: 10.1007/s00066-015-0928-x. Epub 2015 Dec 28.
citation: Chasseray M, Dissaux G, Bourbonne V, Boussion N, Goasduff G, Malloreau J, Malhaire JP, Fournier G, Tissot V, Pradier O, Valeri A, Schick U. Dose to the penile bulb and individual patient anatomy are predictive of erectile dysfunction in men treated with 125I low dose rate brachytherapy for localized prostate cancer. Acta Oncol. 2019 Jul;58(7):1029-1035. doi: 10.1080/0284186X.2019.1574981. Epub 2019 Feb 14.
citation: Sun Y, Qiu W, Yuan J, Romagnoli C, Fenster A. Three-dimensional nonrigid landmark-based magnetic resonance to transrectal ultrasound registration for image-guided prostate biopsy. J Med Imaging (Bellingham). 2015 Apr;2(2):025002. doi: 10.1117/1.JMI.2.2.025002. Epub 2015 Jun 24.
citation: Crook JM, Gomez-Iturriaga A, Wallace K, Ma C, Fung S, Alibhai S, Jewett M, Fleshner N. Comparison of health-related quality of life 5 years after SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial. J Clin Oncol. 2011 Feb 1;29(4):362-8. doi: 10.1200/JCO.2010.31.7305. Epub 2010 Dec 13.