Micro-ultrasound-Guided Focal Laser Ablation (MicroUSgFLA) Treatment for Management of Intermediate-Risk Prostate Cancer: Evaluation of Safety and Effectiveness
Phase: NA
Conditions: Prostate Cancer (Adenocarcinoma), Low and Intermediate Risk Prostate Cancer
Sponsor: University Health Network, Toronto

 
- CONFIDENTIAL -  
 
 
Protocol MicroUSgFLA 001 Version Date: 16 Nov 2022 
 
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Protocol Number:  
MicroUSgFLA 001 
 
Protocol Title: 
Micro-ultrasound-Guided Focal Laser Ablation (MicroUSgFLA) 
Treatment for Management of Intermediate-Risk Prostate Cancer: 
Evaluation of Safety and Effectiveness 
 
 
Study Team: 
 
Principal Investigator 
Dr. Sangeet Ghai 
 
 
Joint Department of Medical Imaging 
 
 
University Health Network 
 
 
 
 
Co-Investigators: 
 
 
Dr Nathan Perlis 
 
 
Division of Urology, Dept of Surgical Oncology 
 
 
Princess Margaret Cancer Centre 
 
 
 
Dr. Antonio Finelli 
 
 
Surgical Oncology/Urology 
 
 
Princess Margaret Cancer Centre  
 
 
 
Dr. Stuart McCluskey 
 
 
Anesthesiology 
 
 
Toronto General Hospital 
 
 
 
Dr. Theodorus van der Kwast 
 
 
Pathology 
 
 
University Health Network 
 
 
 
 
Dr Mark Gertner 
 
 
Joint Department of Medical Imaging 
 
 
 
 
University Health Network 
 
 
 
Dr Robert Weersink 
 
 
Institute of Biomaterials and Biomedical Engineering 
 
 
University Health Network 
 
 
 
 
  

 
 
 
 
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Objective: 
The main objective of this study is to evaluate the safety and 
effectiveness of MicroUS-guided focal prostate cancer (PCa) laser 
ablation. 
 
Study Population: Males, ages 40-85 with biopsy confirmed, organ-confined 
intermediate-risk (Gleason score 7 (3+4, 4+3), no Grade 5 pattern) 
early clinical stage PCa (T1c or T2, N0, M0) and identifiable lesion 
on multi-parametric-MRI (mp-MRI) and MicroUS, with a PSA of < 
15ng/mL, who have not yet undergone pelvic radiation or hormonal 
deprivation therapy and who may not wish to pursue these 
treatments, radical prostatectomy or Active Surveillance at this time. 
 
Study Design:  
6 month, prospective, interventional single-arm safety and 
effectiveness study (patients would continue to be followed as per 
Active Surveillance protocol following completion of the study). 
 
Treatment Extent: Less than 30% of the gland will be treated. Treatment will include the 
Index Lesion visible on MRI and also visible on MicroUS plus 
margins of 8 to 10 mm; tumour-free margins will not extend beyond 
the posterior aspect of the prostate capsule. Urethral and bilateral 
neurovascular bundle preservation will be preferred whenever 
clinically justified. 
 
Population Size:  7 men. 
 
 
Primary Outcome Measure: This study will evaluate the safety and feasibility of 
focal MicroUSgFLA in patients with organ-confined intermediate-risk PCa. 
Feasibility measures will include time taken to treat in the span of a typical 
operating room-like minimally-invasive procedure (Treatment schedule pg. 10), the 
ability to guide the insertion trocars to the target easily under Micro-ultrasound 
guidance and the continued compliance of study participants to complete follow-
up tests and questionnaires. 
To assess the treatment effect on patients' Quality of Life (QoL) the following 
validated self-reported urogenital functioning assessment instruments will be used 
before, and following treatment at 3- and 6-months. 
a. Urinary symptoms – IPSS. 
b. Urinary continence - ICIQ-UI-SF. 
c. Sexual function - IIEF-15. 
PSA levels and post-treatment PSA kinetics will also be assessed. 

 
 
 
 
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Safety Outcome Measure 
Occurrence of any treatment associated adverse events during and after treatment, 
classified according to Clavien-Dindo and CTCAE Version 5.0. 
Secondary Outcome Measure:  
1. The proportion of patients with organ-confined intermediate-risk PCa 
undergoing focal MicroUSgFLA treatment free of clinically significant PCa at 6 
months, which requires definitive treatment. 
2. The proportion of patients with negative 6-month follow-up biopsy results in the 
treated part of the prostate. 
3. The final extent of ablation directly under therapy measured with assistance of 
MicroUS (and ultrasound contrast agents). 
4. The extent of ablation as measured after approximately 5 days with MRI. 
 
INTRODUCTION 
Prostate cancer (PCa) is the most common cancer in men. A recent study of over 18,000 
healthy men has shown a 24.5% cumulative histology prevalence of the disease in 
healthy men over 45 years.1,2 It is estimated that 248,530 new cases of PCa will be 
diagnosed clinically in the U.S.A. in 2021, with 34,130 men dying of the disease.3 Similar 
proportional statistics apply to Canada. The discordance between histology prevalence, 
clinical incidence, and mortality forces a reappraisal of the conventional treatment 
modalities radical prostatectomy, radiation therapy, brachytherapy and hormone therapy 
because they are associated with the possibility of severe side effects such as bladder 
dysfunction and impotence,4,5 osteoporis and risk of fracture6 to name a few. 
Given the indolent nature of many PCa’s another option is Active Surveillance, in which 
the cancer is simply tracked over time with periodic imaging and biopsy, thus avoiding the 
side effects of active treatment but at the potential expense of missing an opportunity for 
cure with the risk of subsequent catastrophic disease progression and death.7 
Ideally the patient with early-stage PCa should have a treatment option that is curative, 
minimally or non-invasive, single session and is associated with none of the side effects 
mentioned above. Minimally invasive focal therapy, which involves the image-guided 
application of a therapeutic source such as high-intensity ultrasound, high power laser 
light or microwave radiation, intended to thermally coagulate the tumour by raising it to a 
temperature of greater than 55°C for several minutes while leaving the remainder of the 
prostate untouched is an attractive option, and indeed there is much evidence of the 
promise of focal therapy of the prostate in the literature8,9,10 and with our group’s 

 
 
 
 
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experience in UHN-REB approved protocols for both MRI- and trans-rectal ultrasound 
(TRUS)-guided interstitial laser prostate focal therapy. 
In protocol 08-0926-c, 4 patients were treated with TRUS-guided laser focal ablation 
through a transperineal approach followed 1-2 weeks later with radical prostatectomy. 
The prostate was carefully step sectioned and whole-mount pathology was compared 
with imaging, confirming that the laser created a confluent burn, limited to the prostate, 
with no viable tumour cells in the ablated volume. Only one patient suffered a mild adverse 
event (self-limited constipation).11 In protocol 06-0670-c, 12 patients were treated with 
transperineal interstitial laser therapy under TRUS guidance and no patient experienced 
peri-operative or post-operative complications, with all maintaining potency and 
continence levels.12 In both these studies, the tumour target was identified on multi-
parametric MRI (mpMRI, consisting of T2-weighted, diffusion-weighted and dynamic 
contrast agent-enhanced imaging), and images at the ultrasound-guided FLA procedure 
were fused to the MR images using in-house image fusion software to locate the target 
accurately since standard TRUS on its own is not a reliable tool to identify a tumour 
against the backdrop of normal prostate parenchyma. 
Employing a completely MRI-based imaging and transperineal treatment guidance 
platform, under protocol 08-0926 54 patients were treated successfully with MR-guided 
focal laser ablation (MRgFLA), with the vast majority experiencing no significant impact 
on urinary continence, erectile function or obstructive symptoms, and approximately 70% 
having a favourable oncologic outcome (manuscript in preparation). The same treatment 
under protocol 15-9002 with longer follow-up is underway in 50 more patients with 
intermediate-risk PCa and continues to show much promise. 
Micro-ultrasound 
While MRI has shown utility in identifying suspicious cancerous lesions within the prostate 
where traditionally, barring very obvious hypoechoic lesions conventional TRUS has not, 
a new ultrasound platform known as micro-ultrasound (MicroUS) is showing promise for 
detecting clinically significant PCa lesions. Studies have shown it to be comparable to 
MRI in detection of clinically significant PCa.13 To the patient it is no different from a 
standard TRUS imaging system; an ultrasound console situated beside the bed operated 
by the physician or ultrasound technologist and a trans-rectally-inserted ultrasound probe. 
What is different is that this ultrasound operates at a much higher frequency of sound 
than standard TRUS (though the acoustic power output is no different). Standard TRUS 
probes operate at a centre frequency of 6 to 9 MegaHertz (MHz) with frequency 
bandwidths of approximately 45%, but the MicroUS probe operates at a centre frequency 
of 21 MHz, with a 75% frequency bandwidth 13 MHz – 29 MHz providing a 300% 
improvement in spatial resolution of the image, down to 70 microns. At this increased 
frequency, subtle features of the tumour that are not identifiable with standard TRUS 
become discernable and distinguishable from non-cancerous prostate tissue. 

 
 
 
 
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Evidence from a large randomized clinical trial (clinical trials.gov ID NCT02079025) 
suggests that the MicroUS system is more sensitive than conventional TRUS to detect 
PCa. During the course of the RCT, the PRI-MUS (Prostate Risk Identification Using 
Micro-Ultrasound)14 scoring system was developed and validated to assess the risk of 
PCa for targeted biopsy with the MicroUS platform, similar to the PIRADS scoring system 
for suspicious areas on mpMRI.15 Some sonographic features described in PRI-MUS 
were also noted to correlate with histo-pathology subtypes such as cribriform pattern, 
which have prognostic implications for patients. 
In a recent feasibility study comparing conventional TRUS, MicroUS and MRI in 9 Active 
Surveillance patients, MicroUS outperformed mpMRI by detecting 89% of clinically 
significant PCa lesions compared to 56% by mpMRI. There were four clinically significant 
PCa lesions (Gleason score ≥ 3+4) that were prospectively detected by MicroUS but not 
on mpMRI.16 One of the postulated reasons for superior sensitivity of MicroUS may be 
that small infiltrative tumours intermixed with normal tissue may not show restricted 
diffusion on diffusion-weighted imaging and therefore may not be detected on mpMRI.17 
MicroUS-guided biopsy in the Princess Margaret Cancer Centre continues under UHN 
REB-approved Protocol Micro-US/MRI 001, performed by an Interventional Radiologist 
(SG) with 17 years experience performing TRUS prostate biopsies and 3 years and 
approximately 200 patients experience performing MicroUS-guided imaging and 
biopsies, with confidence at identifying the sonographic features typical of suspicious 
lesions at high frequency. 
 
Motivation for this study 
Performing interstitial laser thermal therapy in a simpler setting than MRI but with equally 
reliable abilities to visualize and target the tumour is being investigated in this pilot study 
of 7 patients. The ability to reliably destroy the tumour target under MicroUS guidance 
while sparing damage to surrounding critical structures, as with MRgFLA, in this small 
cohort will be extremely suggestive of the promise of MicroUS-guided FLA 
(MicroUSgFLA) in treating foci of localized PCa in the greater population. It would spare 
the expense of procedures performed under MRI guidance, would allow for treatment of 
men in remote communities that might not have local access to MRI imaging and 
treatment delivery systems, and operator expertise, and would allow those who are 
contraindicated for MRI due to such conditions as severe claustrophobia or metallic 
implants to still receive treatment, under an ultrasound-based platform instead. 
STUDY OBJECTIVES 
The main objectives of this study are to evaluate the safety, and effectiveness of 
MicroUSgFLA of the tumour based on mp-MRI and biopsy of the treated area at 6 months. 
Treatment will include the PCa lesion, which must be visible on MRI and MicroUS plus 
negative margins of 8 to 10 mm; margins will not extend beyond the posterior aspect of 
the prostate capsule. 

 
 
 
 
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INVESTIGATOR 
The investigators have the overall responsibility for the conduct and compliance of this 
clinical trial according to this protocol and Good Clinical Practices. 
 
ADMINISTRATIVE REQUIREMENTS AND QUALITY ASSURANCE 
 
Research Ethics Board (REB) 
This protocol and its associated Informed Consent form must be reviewed and approved 
by the appropriate Research Ethics Board (REB) associated with the study site. All 
protocol amendments must be approved by the REB prior to their implementation. A copy 
of the letter signed by the Chair of the REB to the Principal Investigator indicating REB 
approval of the protocol must be received by the PI and maintained in the study file prior 
to study initiation. 
Informed Consent 
The risks and benefits of participating in the study will be explained to each potential 
patient prior to entering into the study. The Principal Investigator’s designee must obtain 
a signed Informed Consent Form for each patient. Receipt of the signed Informed 
Consent Form will be documented in the Case Report Form and a copy retained by the 
Investigator. A copy of the signed Informed Consent Form is given to each patient. 
Reports to REB/Ethics Committee (EC) 
The Investigator will make an accurate and adequate final report to the REB within one 
(1) month after completion or termination of the study. 
STUDY DESIGN 
General design 
This is a single centre, single-arm, open-label study to evaluate the safety and feasibility 
of MicroUS-guided focal PCa laser ablation in patients with organ-confined intermediate-
risk PCa who have not yet received treatment for their cancer. Patients fulfilling the 
inclusion criteria, having none of the clinical exclusion criteria and who may not wish to 
pursue whole gland therapy or Active Surveillance at this time will be enrolled into the 
study after they (or their legal representative) have signed the Informed Consent Form. 
No control group will be utilized and all patients will receive MicroUS-guided FLA for their 
focal PCa. As part of the screening process, patients will provide a medical history, blood 
and urine samples, and undergo a physical examination including a digital rectal 
examination (DRE). At the first visit, patients will also be given a copy of the Informed 

 
 
 
 
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Consent and a copy of QoL and performance questionnaires to assess urinary and 
erectile function (IPSS and ICIQ-UI-SF questionnaires for urinary function, IIEF-15 
questionnaire for erectile function). Men with a single focus of disease ≤15mm suspected 
on standard of care MRI will undergo prostate biopsy using either a standard frequency 
ultrasound machine with or without the MRI-TRUS fusion device Artemis 2.0, at the 
physician’s discretion, or under MicroUS guidance. A systematic biopsy consisting of 12 
cores to 12 sectors plus an additional 2-4 cores targeted to any MRI/MicroUS suspicious 
finding will be performed. For inclusion, all patients will have MRI and prostate biopsy 
within 12 months of treatment. On preoperative examination (Visit 1) - blood and urine 
samples will be taken. If the screening biopsy was not performed with the MicroUS device 
then a MicroUS imaging session will be performed at Visit 1 to be sure that the tumour 
target is visible on MicroUS (it will be known a priori that the tumour target is visible on 
MicroUS if the screening biopsy was performed with this device). At Visit 2 – the focal 
treatment will be performed under appropriate anesthesia (regional or general 
anesthesia, or conscious sedation, as determined by the anesthesiologist) - in the TGH 
research Interventional Radiology suite (or similar facility). The treatment is expected to 
last approximately 2-3 hours, and patients are not expected to experience any pain during 
the procedure. Laser ablation will be monitored by real-time ultrasound tracking of the 
ablation zone and ensuring that treatment does not extend to critical structures, and by 
one or more temperature probes placed into the prostate in the vicinity of the target 
treatment area. At the physician’s discretion, an additional one or more temperature 
probes will be placed at the rectoprostatic angle to monitor the temperature close to the 
rectum as a precautionary measure. 
At the physician’s discretion, a contrast agent-enhanced MicroUS scan will be performed 
during and/or immediately after the procedure as an additional way to track the ablation 
volume, by demonstrating a lack of enhancement of the ultrasound signal within the 
ablation volume due to the coagulated and locally sealed blood vessels against the 
backdrop of enhancing, unaffected prostate tissue. The contrast agent will be 
administered by intravenous injection using the existing iv-access catheter that was 
placed by the anesthesiologist, and the MicroUS device will be set to the contrast agent 
imaging mode. 
The size and location of the ablation volume will be measured and compared to the 
planned target volume and the proximity of the lesion to the urethra and rectum. If the 
ablation volume does not encompass the target volume and is still a safe distance from 
either critical structure, FLA may be continued or repeated. 
After the treatment the patient will be transferred to an appropriate recovery area for 
monitoring. Patients will be able to return home the day of the procedure. 
On days 5 (+/- 3 days), 90 (+/- 7 days) and 180 (+/- 14 days) following the procedure, 
patients will be assessed for clinical signs of urinary, rectal, and erectile complications 
and will complete validated self-assessment tools for these functions at days 90 and 180. 
All patients will undergo mpMRI of the prostate at day 5 (+/- 3 days) following treatment 

 
 
 
 
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to confirm that ablation covered the tumour target. Free/Total PSA will be monitored at 
the preoperative examination (Visit 1) and after treatment at days 90 and 180 (Visits 4 
and 5), in order to try to understand the initial effect of MicroUSgFLA on PSA. Six months 
after the procedure (Visit 5),a study biopsy using MicroUS or the fusion device Artemis 
2.0 will be performed with 3-8 needle cores aimed to the ablated lesion and the margins 
surrounding it to verify the oncological effectiveness of the treatment. 
Study duration 
The duration of the study for each patient is 6 months. 
Number of patients 
Seven (7) patients will be enrolled in this study. All patients who are eligible will be 
evaluated for inclusion. 
Stopping rules 
The study will be discontinued if an unwanted effect (adverse event) related to the 
procedure is considered severe by the Investigator and/or the Research Ethics Board and 
endangers the health of enrolled patients. 
PROCEDURES OF THERAPY 
 
Tumour localization 
Eligible patients will have a transrectal, ultrasound-guided biopsy-confirmed PCa, with 
NCCN intermediate-risk characteristics (primary Gleason score ≤ 4, maximum Gleason 
score 7, and PSA below 15 ng/mL). Specific tumour location will be confirmed by mpMRI 
with all images reviewed by a single radiologist (SG) experienced in prostate MRI 
interpretation. Following the MRI, patients will undergo MicroUS imaging to locate the 
same lesion for biopsy or, if the biopsy is performed with a standard frequency ultrasound 
device then MicroUS imaging will be performed only to be sure the tumour target can be 
visualized on MicroUS, prior to proceeding to therapy. 
Light delivery 
The insertion location of the laser applicator(s) will be performed tranperineally and 
determined according to maximum overlap between the expected treatment zone and the 
location of the tumour as determined by the MRI and MicroUS analysis. The light dose 
will be determined based on previous experience from MRI-guided Laser Interstitial 
Thermal Therapy. 
Light source and light delivery laser applicator 

 
 
 
 
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The laser unit and laser applicators to be used in this study are part of the CLS 
TRANBERG® Thermal Therapy System which is FDA approved, is indicated for use in 
surgical applications requiring the ablation, vaporization, excision, incision and 
coagulation of soft tissue, and which has already been UHN-REB approved for use in our 
MRgFLA clinical trials. 
Details of its operation and technical specifications are listed in Protocol 15-9002. Briefly, 
a variable power diode laser feeds laser light at the wavelength 1064 nm into tissue 
through an interstitially placed sterile optical fibre (laser applicator). At this wavelength, 
the light is preferentially absorbed by tissue, creating an elevated temperature and thus 
thermal coagulation. Coagulation of the tumour ensures no bleeding or collateral damage 
and the diffusing tip design reduces the possibility of charring of the tissue. 
Laser applicator and temperature probe insertion 
The placement of the light-delivery laser applicators will be performed transperineally into 
the prostate for the treatment of PCa. Following appropriate anesthesia, the patient will 
be placed in a semi- or full-lithotomy position, to be decided at the physician's discretion, 
the insertion area will be disinfected and draped, and the single use devices will be 
inserted into the patient’s perineum under MicroUS guidance until they reach the target. 
Specifically, an insertion catheter is first placed into the prostate by means of a stiff trocar 
contained within. Once the catheter has arrived at the target site the trocar is removed 
and the laser applicator is inserted. The catheter is then retracted a few centimetres, 
enough to expose the light diffusing part of the laser applicator. The entire process is 
monitored by MicroUS to ensure the laser applicator arrives at, and remains at the tumour 
target. The design allows light to emanate 360o around its circumference into the 
surrounding tissue, creating a coagulation volume in the shape of a sphere or an ellipse. 
The maximum laser power to be used in this protocol is 15W, and the power can be 
adjusted based on MicroUS and temperature monitoring. The temperature probes are 
inserted in a similar manner to the laser applicators; the connectors of these probes attach 
to the laser base unit which converts the returned signal into temperature and displays 
this in real time. In practice, the patient will undergo a total of 2 to 8 trans-perineal 
punctures. 
During the previous interstitial photo-thermal focal therapy studies, conducted safely with 
no side effects, the placement of laser applicators went without difficulty and none of the 
procedures had to be stopped due to excessive heat in neighbouring structures (urethra 
or rectum), which can be evaluated by tissue temperature probes placed at the recto-
prostatic angle. 
Procedures to protect the bladder and rectum 
The primary approach to ensure that the bladder, rectum, and urethra do not receive a 
significant interstitial laser thermal dose will be to limit the light fluence reaching these 

 
 
 
 
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structures through the accurate and verified placement of the laser applicators under 
MicroUS guidance. It has been established in pre-clinical studies that the zone of laser 
thermal damage in the prostate is sharply delineated.18 The planned size of the damage 
zone will be based on the previous UHN-REB approved studies conducted by our group. 
These studies indicate that the typical ablation zone diameter is approximately 12±1.7 
mm. The planned treatment volume will encompass the tumour volume plus a margin of 
8 to 10 mm where feasible and safe to do so. Treatment will not extend beyond the 
posterior aspect of the prostate capsule. 
Where these planning rules conflict, the safety margins defined above will take 
precedence. The treatment boundary may extend to the capsule in other regions of the 
prostate. 
Additionally, CLS TRANBERG® tissue temperature probe(s) may be inserted into the 
recto-prostatic angle to further ensure the rectum remains at a safe temperature. 
Treatment schedule 
The schedule and time estimation (in minutes) of the total procedure is provided below: 
Time   
 
 
Action Taken 
0 to 30 
 
Induction of anesthesia, ongoing vital signs monitoring. 
30 to 60  
 
Positioning of the patient, disinfecting, draping, insertion of Foley 
catheter. 
60 to 80  
 
MicroUS probe insertion and tumour visualization/localization and 
treatment planning. 
80 to 100  
 
Insertion and localization of introducers and potential tissue 
temperature probes. 
100 to 120   
Replacement of insertion trocars with laser applicators and 
repositioning of applicator for complete coverage. 
120 to 150   
Illumination, parameter monitoring. 
150 to 160 
Removal of laser applicators, ongoing vital signs monitoring. 
 
Following the procedure and appropriate post-procedure recovery and assessment, the 
patient will be discharged. Catheter removal at the post-procedure day 3 follow up will be 
determined by clinical characteristics and a trial of void will be conducted. All patients will 
be monitored for adverse events on an ongoing basis.  
LABORATORY INVESTIGATIONS 
Standard haematological Tests 
Hemoglobin (mmol/l) 

 
 
 
 
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Red cell count (T/l) 
M.C.V. (fl) 
Haematocrit (%) 
M.C.H. (fmol) 
White cell count (G/l 
Differential white cell count (%) 
Platelet count (G/l) 
Prothrombin Time (sec) 
aPTT (sec) 
 
Standard blood chemistry tests 
Creatinine (micromol/l) 
Specific blood chemistry test 
Prostate-Specific Antigen (PSA) 
Standard urinalysis 
C&S Urine 
 
PATIENT POPULATION 
This study is designed to include 7 patients who have histologically proven organ-
confined intermediate-risk adenocarcinoma of the prostate. 
INCLUSION CRITERIA 
Patients meeting all of the following inclusion criteria will be eligible for the study: 
• 
Men 40-80 years of age. 
• 
Histologically-proven intermediate-risk PCa (Gleason score 7, primary grade ≤ 4). 
• 
PCa clinical stage T1c or T2. 
• 
MRI/MicroUS site suspicious for cancer or cancer mapped to one prostate lobe. 
• 
Maximum dimension of MRI/MicroUS visible tumour ≤15mm. 
• 
Suspicious site on Prostate MRI/MicroUS must coincide with sector positive for 
cancer on biopsy. 
• 
Prostate specific antigen (PSA) level < 15 ng/mL. 
• 
IPSS, ICIQ-UI-SF, IIEF-15 questionnaires completed prior to the procedure. 
• 
Life expectancy of greater than 10 years, based on co-morbidity not related to 
PCa. 
 
EXCLUSION CRITERIA 
Patients with any of the following criteria will be excluded from study participation: 
• 
Maximum dimension of MRI/MicroUS visible tumour > 15 mm. 

 
 
 
 
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• 
Patients medically unfit for focal therapy of the prostate. 
• 
Patients who are unwilling or unable to give informed consent. 
• 
Patients who have received androgen suppression therapy. 
• 
Patients who have received or are receiving chemotherapy for prostate 
carcinoma. 
• 
Patients previously treated with surgery to the prostate (traditional, endoscopic 
or minimally invasive) including HIFU, TUNA, RITA, microwave, cryotherapy or 
any curative treatment. 
• 
Patients who have undergone radiation therapy for PCa or to the pelvis. 
• 
Any condition or history of illness or surgery that, in the opinion of the 
Investigator, might confound the results of the study or pose additional risks to 
the patient (e.g. significant cardiovascular conditions or allergies). 
• 
Patients with a history of non-compliance with medical therapy and/or medical 
recommendations. 
• 
Patients who are unwilling or unable to complete the patient self-assessment 
questionnaires. 
• 
Chronic or acute prostatitis, neurogenic bladder, urinary tract infection, sphincter 
abnormalities, or any other symptom that prevents normal micturition. 
• 
Patients who have participated in a clinical study and/or received treatment with 
an investigational treatment and/or product within the past 90 days.  
• 
Patients with contraindication to MRI (i.e. pacemaker, hip prosthesis, severe 
claustrophobia, brain aneurysm clip, allergy to MRI contrast agent) 
 
EVALUATION OF SAFETY AND TOLERABILITY 
 
Criteria 
The evaluation of safety will be based on reported adverse events, changes in vital signs 
and laboratory tests throughout the course of the study. 
Distinctions will be made between adverse events that are not related to the study 
treatment, related to the study treatment, or related to the technical laser thermal therapy 
procedure. The protocol will be re-evaluated for any serious adverse event that is 
considered related to the study treatment and/or the laser thermal treatment procedure. 
The following specific examinations are scheduled to monitor particular organs or 
functions that require attention following treatment by interstitial laser thermal therapy: 
• Urinary function (specific Inclusion Visit and post-treatment evaluations including 
patient questionnaires (IPSS), ultrasound and MR Imaging, and urinalysis). 
• Urinary Continence, ICIQ-UI-SF. 

 
 
 
 
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• Erectile function will be monitored with a specific IIEF-15 questionnaire. 
Adverse events 
Each patient must be carefully monitored for adverse events. This includes abnormal 
laboratory values that are outside the parameters of the protocol or are considered 
clinically significant by the Investigator. An assessment for adverse events must be made 
regarding the seriousness, intensity and relationship to the FLA. 
Adverse events (AEs) are illnesses, signs or symptoms that have appeared or worsened 
during the course of the study. All AEs volunteered by the patient or elicited by the 
Investigator must be recorded. All AEs must be recorded whether or not they are 
considered by the Investigator to be treatment and/or procedure-related. Whenever the 
Investigator is confident of the diagnosis, he/she should group together related signs, 
symptoms and abnormal laboratory test results as a single illness. 
Patients experiencing AEs that result in discontinuation from the study or that are ongoing 
at the end of the study should have appropriate follow-up until such time as the event 
resolves, the patient's condition stabilizes, or until it is determined that the event is not 
due to the test device procedure. 
A serious adverse event (SAE) means any complication whose clinical significance is 
greater than anticipated, or which occurs with a frequency greater than is usually seen 
and reported for this type of treatment. 
Criteria for SAE may also include the following: 
• Is life threatening. 
• Prolongs hospitalization. 
• Results in permanent impairment of a bodily function or permanent damage to the 
body structure. 
• Necessitates immediate medical or surgical treatment to preclude permanent 
damage or impairment. 
Unanticipated adverse events means any SAE that was not previously identified in nature, 
severity or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problems 
associated with a device that relates to the rights, safety, or welfare of patients.   
In the event of an incident that is related to a failure of the device or a deterioration in its 
effectiveness, or any inadequacy in its labelling or in its directions for use and has led to 
the death or a serious deterioration in the state of health of a patient, user or other person, 
or could do so were it to recur, report the incident and the circumstances surrounding it 
to the Director and the manufacturer or importer of the device, within 72 hours after its 
discovery. 

 
 
 
 
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Any other serious and unanticipated adverse device effects noted during the study should 
immediately be evaluated and reported no later than ten (10) working days to the 
reviewing REB. 
The contact person for this study is: 
Dr. Sangeet Ghai 
University Health Network, Toronto General Hospital,  
1PMB 292 
Toronto, Ontario 
Canada, M5G 2M9 
Phone:  (416) 340-4800 x 4656 
Fax:  (416) 946-2771 
Emergency Contact: (416) 340-3155 
 
The following should be determined and recorded on the case report forms: 
(1) 
frequency 
(2) 
severity 
(3) 
type 
(4) 
relation to thermal therapy 
(5) 
action taken 
(6) 
outcome 
 
The severity of the adverse event will be characterized as mild, moderate or severe as 
follows: 
Mild - effects are usually transient, requiring no special treatment and not interfering with 
the subject's daily activities. 
Moderate - effects usually introduce a low level of inconvenience or concern to the 
subject and may interfere with daily activities but are generally alleviated by simple 
therapeutic measures. 
Severe - effects interrupt a subject's daily activities and usually require systemic drug 
therapy or other treatment. 
Every effort should be made to determine the cause of each AE since a judgment must 
be made as to whether or not it is related to the interstitial laser thermal therapy 
procedure. The relation needs to be graded and recorded on the case report form as 
follows: 

 
 
 
 
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Not Related - the AE is due to the underlying disease state or is due to concomitant 
medication or therapy not related to the interstitial laser thermal therapy. 
Possibly Related - the AE had a minimal temporal relationship to the interstitial laser 
thermal therapy and/or an alternative etiology is more likely. 
Probably Related - the AE had a strong temporal relationship to the interstitial laser 
thermal therapy and alternative etiology is less likely compared to the potential 
relationship to the interstitial laser thermal therapy. 
Definitely Related - the AE had a strong temporal relationship to the interstitial laser 
thermal therapy, and another etiology is unlikely. 
Unknown - temporal relationship to the interstitial laser thermal therapy cannot be 
determined and alternative etiology is equal compared to the potential relationship to the 
interstitial laser thermal therapy. 
DISCONTINUATION FROM STUDY 
Patients may be withdrawn for any of the following reasons: patient choice, patient non-
compliance, patient loss to follow-up, serious adverse effect, severe illness, need for re-
treatment or Investigator decision. 
DATA COLLECTION 
Case report form completion 
A Case Report Form (CRF) will be provided for each subject. CRFs will be completed in 
a timely manner by study personnel. All fields and blanks must be completed. If an entry 
on the CRF needs to be changed during the study, the correction will be made as follows: 
• 
Draw a single line through the incorrect entry leaving it identifiable, and enter the 
correct information. 
• 
Date and initial the change. 
• 
White-out or erasure on the CRF is not permitted under any circumstances. 
The following abbreviations will be used when values or answers cannot be provided: 
 
 
 
NA  = Not Applicable 
 
 
 
ND  = Not Done 
 
 
 
UNK = Unknown 
 
Reporting and recording of data 

 
 
 
 
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All study data will be recorded on the Case Report Forms (CRF). All CRFs must be made 
available to the Study Monitor as soon as they have been completed so that the validity 
and completeness of the forms can be determined. If possible, all CRF data should 
originate from a verifiable medical record. All data should be recorded in black ink on the 
CRF for ease of duplication, interpretation and analysis. Any corrections should be made 
by scoring through the original value with a single line and writing the new value next to 
the initial entry with the Investigator initialling and dating the new entry. 
Only the Investigator or designated staff may amend or otherwise alter any data entered 
onto the CRF. Also, any changes must be made on all copies of the document so that 
there is no difference between copies. If the reason for the correction is not apparent, 
then when appropriate, a brief explanation of the reason for the correction should be 
made. Correction fluids should never be used on any document. 
DATA HANDLING, RECORD KEEPING AND RETENTION 
A copy of all study data and documentation must be retained in the files of the responsible 
Investigator for 10 years. The information will be kept in a locked and secure area by the 
Principal Investigator. Only the study team and representatives of the University Health 
Network, including the Research Ethics Board will have access to the study-related 
records. 
All information collected during the study, including personal health information, will be 
kept confidential and will not be shared with anyone outside the study unless required by 
law. The patient will not be named in any reports, publications, or presentations that may 
arise from this study. 
The subject's recruitment information along with medical record number will not be stored 
along with the patient's CRF binder. It will be kept in the study coordinator's office during 
the study. All files of screen failure subjects and the CRFs of the patients who complete 
the study will be transferred and stored within PMCC for 10 years. 
If the Principal Investigator retires, relocates or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who 
will accept responsibility. 
PROTOCOL DEVIATIONS 
In medical emergencies, the Investigator will use medical judgment and remove the 
participant from immediate hazard, then notify the REB regarding the type of emergency 
and course of action taken. Any other changes or deviations from the protocol will be 
made as an amendment to the protocol and must be approved by the REB before being 
implemented. 
REPORTING & PUBLICATION OF RESULTS 

 
 
 
 
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Results will be published in a peer-reviewed journal(s). 

 
 
 
 
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REFERENCES 
 
1. 
Thompson, I. M., Goodman, P. J., Tangen, C. M. et al.: The influence of 
finasteride on the development of prostate cancer. New England Journal of 
Medicine, 349: 215, 2003 
 
2. 
Thompson, I. M., Pauler, D. K., Goodman, P. J. et al.: Prevalence of 
prostate cancer among men with a prostate-specific antigen level <= 4.0 ng per 
milliliter. New England Journal of Medicine, 350: 2239, 2004 
 
3. 
Cancer Society Facts and Figures 2021. American Cancer Society Inc., 
2021. 
 
4. 
Potosky, A. L., Davis, W. W., Hoffman, R. M. et al.: Five-year outcomes 
after prostatectomy or radiotherapy for prostate cancer: The prostate cancer 
outcomes study. Journal of the National Cancer Institute, 96: 1358, 2004 
 
5. 
Alibhai, S. M. H., Naglie, G., Nam, R. et al.: Do older men benefit from 
curative therapy of localized prostate cancer? Journal of Clinical Oncology, 21: 
3318, 2003 
 
6. 
McLeod, D. G., Iversen, P., See, W. A. et al.: Bicalutamide 150 mg plus 
standard care vs standard care alone for early prostate cancer. Bju International, 
97: 247, 2006 
 
7. 
Johansson, J. E., Andren, O., Andersson, S. O. et al.: Natural history of 
early, localized prostate cancer. Jama-Journal of the American Medical 
Association, 291: 2713, 2004 
 
8. 
Reddy, D., Bedi, N. and Dudderidge, T.: Focal therapy, time to join the multi-
discipinary team discussion?. Transl Androl Urol, 9: 1526, 2020. 
 
9. 
Wenger, H., Yousef, A., Oto, A. and Eggener, S.: Laser ablation as focal 
therapy for prostate cancer. Curr Opin Urol, 24: 236, 2014. 
 
10. 
Guillaumier, S., Peters, M., Arya, M. et al.: A multicentre study of 5-year 
outcomes following focal therapy in treating clinically significant nonmetastatic 
prostate cancer. Eur Urol, 74: 422, 2018. 
 
11. 
Lindner, U., Lawrentschuk, N., Weersink, R.A. et al.: Focal laser ablation 
for prostate cancer followed by radical prostatectomy: validation of focal therapy 
and imaging accuracy. Eur Urol, 57: 1111, 2010. 

 
 
 
 
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12. 
Lindner, U., Weersink, R.A., Haider, M.A. et al.: Image guided photothermal 
focal therapy for localized prostate cancer: phase I trial. J Urol, 182: 1371, 2009. 
 
13.  
Klotz, L., Lughezzani, G., Maffei, D. et al.: Comparison of micro-ultrasound 
and multiparametric magnetic resonance imaging for prostate cancer: A 
multicenter, prospective analysis. Can Urol Assoc J, 15: E11, 2021. 
 
 
14. 
Ghai, S., Eure, G., Fradet, V. et al.: Assessing cancer risk on novel 29 MHz 
micro-ultrasound images of the prostate: creation of the micro-ultrasound protocol 
for prostate risk identification. J Urol, 196: 562, 2016. 
 
15. 
Weinrib, J.C. et al.: PI-RADS prostate imaging-reporting and data system: 
2015, version 2. Eur Urol, 69: 16, 2016. 
 
16. 
Eure, G., Fanney, D., Lin, J. et al.: Comparison of conventional transrectal 
ultrasound, magnetic resonance imaging, and micro-ultrasound for visualizing 
prostate cancer in an active surveillance population: a feasibility study. Can Urol 
Assoc J, 13: E70, 2019. 
 
17. 
Langer, D.L. et al.: Intermixed normal tissue within prostate cancer: effect 
on MR imaging measurements of apparent diffusion coefficient and T2-sparse 
versus dense cancers. Radiol, 249: 900, 2008. 
 
18. 
Peters, R.D., Chan, E., Trachtenberg, J. et al.: Magnetic resonance 
thermometry for predicting thermal damage: An application of interstitial laser 
coagulation in an in vivo canine prostate model. Mag Res Med, 44: 873, 2000. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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1. APPENDIX A: SCHEDULE OF EVENTS 
 
Procedure 
Screening Visit 1 
Visit 2 
FLA 
Procedure 
 
 
Visit 3 
Post-
Focal 
 Day 5 
(+/- 3 
Days) 
 
Visit 4 
Month 
3 
(+/- 7 
Days) 
 
Visit 5 
Month 
6 
(+/- 14 
Days) 
 
 
Screening/Inclusion 
Pre-op 
Consult. 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Physical Exam 
X 
 
 
X 
 
X 
X 
Medical History 
X 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
DRE 
X 
 
 
 
 
X 
MRI 
 
 
 
X 
 
X 
MicroUS for Biopsy 
or Confirmation of 
Tumour Target 
Visibility 
X 
 
 
 
 
 
Biopsy 
 
 
 
 
 
X 
Catheter removal 
 
 
 
X 
 
 
PSA Level 
X 
 
 
 
X 
X 
Free/Total PSA 
X 
 
 
 
X 
X 
Urinalysis 
X 
 
 
 
X 
X 
Blood Chemistry 
and Hematology 
X 
 
 
 
 
 
Adverse Events 
X 
 
X 
X 
 
X 
X 
 
Vital Signs 
X 
 
X 
X 
 
X 
X 
 
Patient 
Questionnaires 
X 
 
 
 
X 
X 
Concomitant 
Medications 
X 
 
X 
X 
 
X 
X 
 
Meeting with 
Study Anesthetist 
 
X