Short-term Efficacy of Transperineal Laser Ablation (TPLA) With Image Fusion and Multi-parametric (mpMRI) Follow-up in Focal Low-intermediate Risk Prostate Cancer: Interventional Pilot Study
Phase: NA
Conditions: Prostate Cancer
Sponsor: University of Rome Tor Vergata

 
 
 
Study Protocol Cover Page Official Study Title: : Efficacy of Eco-guided Percutaneous 
Transperineal Ablation with Neodymium Laser in Patients with Low-Intermediate Risk Prostate 
Cancer: Non-Pharmacological Interventional Study  
R.S 68:19  
Approval date: 07/09/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Extension on long-term efficacy of 
Focal Laser Ablation for Prostate Cancer 
among a multicenter registry 
 
A multi-center international registry to evaluate the TPLA-TRLA treatment, new Focal Laser 
Ablation modality, of focal prostate cancer with regards to long-term efficacy, functional 
outcomes and safety. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 – 9 July 2019 
 
 
 
PROTOCOL TITLE ‘Protocol Extension on long-term efficacy of TPLA for Prostate Cancer 
among a multicenter registry’ 
 
Short Title 
Registry FLA for Pca 
Version 
1.2 
Date 
July 9th, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
TABLE OF CONTENTS 
1. 
INTRODUCTION AND RATIONALE .............................................................................. 7
2. 
OBJECTIVES ................................................................................................................. 7
3. 
STUDY DESIGN ............................................................................................................ 7
4. 
STUDY POPULATION ................................................................................................... 8
4.1 Population (base) .................................................................................................... 8
4.2 Inclusion criteria ...................................................................................................... 8
4.3 Exclusion criteria ..................................................................................................... 8
5. 
METHODS ..................................................................................................................... 8
5.1 Study parameters/endpoints .................................................................................... 8
5.1.1 Main study parameter/endpoint ........................................................................ 8
5.1.2 Secondary/endpoints ........................................................................................ 8
5.2 Study duration ......................................................................................................... 9
5.3 Description of data to be collected ........................................................................... 9
6. 
STATISTICAL ANALYSIS .............................................................................................. 9
6.1 Primary study parameter(s) ..................................................................................... 9
6.2 Secondary study parameter(s) ................................................................................ 9
6.3 Handling missing and spurious data .......................................................................10
7. 
ETHICAL CONSIDERATIONS ......................................................................................10
7.1 
Regulation statement .............................................................................................10
7.2 
Recruitment and consent........................................................................................10
8. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .............................10
8.1 
The Steering Committee ........................................................................................10
8.2 Handling and storage of data and documents ........................................................11
8.3 Monitoring and Quality Assurance ..........................................................................12
8.4 
Amendments ..........................................................................................................12
8.5 Public disclosure and publication policy ..................................................................12
9. 
REFERENCES ..............................................................................................................12
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 – 9 July 2019 
 
 
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS 
 
 
DMS 
Data Management System 
eCRFs 
Electronic Case Report Forms 
FLA 
Focal Laser Ablation 
IPSS 
International Prostate Symptom Score 
IQOL 
Incontinence Quality of Life 
METC 
Medical research ethics committee (MREC); 
mpMRI 
Multi-parametric MRI 
Participant 
Centre that is participating in this registry 
PROMs 
Patient reported outcome measures 
SHIM 
Sexual Health Inventory for Men 
TPLA 
Transperineal laser ablation 
TRLA 
Transrectal laser ablation 
VAS 
Visual Analogue Scale 
Wbp 
Personal Data Protection Act 
WMO 
Medical Research Involving Human Subjects Act 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
SUMMARY 
 
 
Rationale: The treatment of low-intermediate risk prostate cancer with focal laser ablation (FLA), a 
new Focal Laser Ablation (FLA) modality, may offer advantages in life quality and functional 
outcomes over current standard therapies. As the technique is relatively new, indications and 
outcomes for this treatment are subject of investigation. Clinical information from these treatments 
can be useful as part of the validation process of this technique. The aim of this registry is to collect 
data on patients treated with transperineal/transrectal laser ablation of the prostate outside clinical 
trials and to provide data on safety and functional outcomes in these patients in order to 
standardize the treatment. 
 
Objective: To assess long-term safety and efficacy of focal laser ablation for low-intermediate 
risk prostate cancer, to assess functional outcomes, to assess safety, to determine baseline 
patient characteristics, to collect information on possible differences between centers applying 
treatment of focal laser ablation and to explore the optimal treatment indications and possible 
limitations. 
 
Study design: This is an international prospective observational registry in which data will be 
recorded of patients who are treated with focal laser ablation low-intermediate risk prostate 
cancer. 
 
Study population: Male patients treated with focal laser ablation for low-intermediate risk 
prostate cancer. 
 
Main study parameters/endpoints: The primary endpoint of this registry is safety and long-
term efficacy (avoidance or postponing of surgery for prostatectomy; benefits of FLA vs 
surgery will be monitored and put into the registry of focal laser ablation for low-intermediate 
risk prostate cancer followed with multi-parametric MRI, measured by the lack of 
histopathological evidence of tumor recurrence during 6-month and 12-month follow-up; 
annual follow-up with mpMRI and biopsies for 5 years. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
1. INTRODUCTION AND RATIONALE 
 
Current treatment options for focal low-intermediate risk prostate cancer is surgery or 
radiotherapy. Treatment side effects and quality of life impairment might hamper patients to 
allow surgical treatment. On the other hand, side effects of radiotherapy eventually include 
damage to the rectum and bladder. A minimal invasive technique with reduced postoperative 
morbidity and equal functional outcomes as standard treatment is desired to solve these 
problems. 
 
The SoracteLite EchoLaser system can be applied for FLA, a new FLA modality, of the 
prostate. The aim of this prospective registry is to collect data on patients treated with FLA 
and to provide data on indications, functional and safety outcomes in these patients in order 
to get more insight in the treatment. 
 
2. OBJECTIVES 
 
- 
To assess long-term efficacy in patients treated with focal laser ablation for 
low-intermediate risk prostate cancer. 
 
- 
To verify if FLA may represent a valid and safe way to postpone or even avoid 
radical prostatectomy 
 
- 
To assess functional outcomes in patients treated with focal laser ablation for 
prostate cancer. 
 
- 
To assess safety outcomes measured by the number intra- and 
postoperative adverse events in patients treated with focal laser ablation. 
 
- 
To determine characteristics of patients treated with focal laser ablation. 
 
- 
To identify possible differences between centers and possible relations between 
treatment application and outcomes. 
 
- 
To explore the optimal indications and possible limitations of FLA for low-intermediate 
prostate cancer. 
 
 
3. STUDY DESIGN 
 
This is an international prospective observational registry in which data on consecutive patients 
with low-intermediate prostate cancer treated with TPLA/TRLA is collected. Centers from any 
country may apply for participation in this registry. Data from each individual patient will be 
collected at the participating centers in a maximum of five years. Patients’ data at baseline and 
follow-up visits will be recorded, as well as data of intra- and postoperative complications. Data 
will be collected through electronic Case Report Forms (eCRFs), with use of an online 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
 
Data Management System (DMS). Investigators or research nurses at local sites will 
complete the eCRFs in the DMS. 
 
The data collection or patient participation in this registry does not interfere with the choice of 
treatment, sample collection, procedures or the treatment itself, which should entirely follow 
standard hospital practice. 
 
4. STUDY POPULATION 
 
4.1 Population (base) 
 
The study population comprises those patients presenting low-intermediate risk prostate 
cancer who are planned to undergo focal laser ablation in the participating centers, after 
completing the primary follow-up. 
 
4.2 Inclusion criteria 
 
Observational data form patients who meet the inclusion criteria will be recorded: 
 
- 
Male (>18 years old) 
- 
Presenting with focal low-intermediate prostate cancer (pTNM T2bN0M0) 
- 
Focal lesion of 2cm or less; Gleason 6-7 (GG1-GG2) 
- 
Signed informed consent form approved by the ethical committee of the University of 
Rome “Tor Vergata”, Italy. 
 
 
4.3 Exclusion criteria 
 
- 
Age < 18 years, urethral stenosis, multi-focal cancer, neurological disturbances 
 
- 
Previous prostatic surgery or radiotherapy 
 
 
5. METHODS 
 
5.1 Study parameters/endpoints 
 
5.1.1 Main study parameter/endpoint 
 
Long-term treatment efficacy measured by the time until possible histopathological 
tumoral recurrence. 
 
 
 
5.1.2 Secondary/endpoints 
 
Experienced functional effectiveness measures by change in Sexual Health 
Inventory for men (SHIM) and (Incontinence Quality of Life) IQoL at 6 and 12 
months initially and annually for 5 years. Decreasing the need for surgical 
prostatectomy and/or radiotherapy. 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
  
Treatment safety measured by the complications at 30 days, according to the Clavein-
Dindo classification. 
 
 
5.2 Study duration 
 
This registry will be open for inclusion for five years. Since individual patients will have a 
follow-up of five years, the total study duration will be 10 years. 
 
Interim analysis will be made and published during the course of the study carried 
out by the principal investigators, depending on the number of patients enrolled. 
 
Earlier termination of the enrollment may also be decided by principal investigators, 
depending on number of patients enrolled. 
 
5.3 Description of data to be collected 
 
Baseline characteristics: age, height, weight, comorbidities, medication use, medical 
history, biopsies, mpMRI: location of tumor, dimension of the tumor, dimension of necrosis 
according to mpMRI, eventual residual dimension. 
 
 
Intra- and perioperative information: procedure duration, device treatment specifications 
(e.g. number of fibers used, power per fiber, energy per fiber, total delivered energy, 
distance between fibers, pull back of the fibers and distance), complications, postoperative 
catheter placement and duration. 
 
Follow-up: symptoms, complications (e.g. retention, fever, hematuria, erectile dysfunction, 
stricture), re-treatment (surgery, radiotherapy or FLA). 
 
6. STATISTICAL ANALYSIS 
 
6.1 Primary study parameter(s) 
 
The mean time until histopathological tumor recurrence. The mean time for the need for 
retreatment including standard deviations. In addition, the percentage of retreatment and 
types of retreatment will be calculated at the end of the registry. 
 
 
6.2 Secondary study parameter(s) 
 
Experienced functional effectiveness is calculated by the change in Sexual Health 
Inventory for men (SHIM) and (Incontinence Quality of Life) IQoL score at different time 
points of the study. 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
 
Other study parameters will be descriptive of baseline characteristics of the patients, 
complications and/or adverse events intra-operative and at 30 and 90 days, medication 
use, hospital stay and functional outcomes. 
 
 
6.3 Handling missing and spurious data 
 
All analyses will be carried out on available data, with reporting of proportions of missing 
data. The University of Rome “Tor Vergata” will perform all analyses using SPSS 24 or 
more recent. Results will be presented in tables reporting the number of subjects, mean, 
standard deviation, minimum and maximum for continuous data; and number of subjects 
and percentages for categorical data. 
 
7. ETHICAL CONSIDERATIONS 
 
7.1 Regulation statement 
 
This registry will be registered at cinicaltrials.gov. This registry may additionally be 
registered at and approved by the competent authorities, when required by local law. The 
local investigator is responsible to perform FLA according to local regulations. 
 
 
7.2 Recruitment and consent 
 
When there is an indication for treatment of low-intermediate risk prostate cancer by FLA, the 
doctor will inform the patient about this registry. The doctor will explain the observational 
character of this registry and that data will only be recorded. There will be no change in the 
treatment or follow-up. Furthermore, data is saved in an encoded way. At any time, the patient 
can refuse or ask to stop the data registration. Data registered until then will remain available 
for research. 
 
The patient will be encouraged to take time to consider participation in the registry. 
Additional questions will be answered. The patient should sign the consent at the 
consultation or at the next appointment. 
 
The participant is responsible for correct informed consent of all subjects before entering 
data into the DMS. 
 
8. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
 
8.1 The Steering Committee 
 
The Steering Committee tasks and responsibilities include: 
 
- 
To review and approve the final protocol and amendments 
 
- 
To select the network of investigators 
 
- 
To monitor progress of registry enrolment of centers 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
- 
To monitor the data collection process 
 
- 
To ensure a scientifically sound and safe conduct of the registry, eventually 
by executing an audit 
 
- 
To review the statistical analysis plan 
 
- 
To guarantee the integrity of data collection and analyses 
 
- 
To address and resolve registry management problems 
 
- 
To assist in the analyses and presentation of the registry results 
 
 
 
8.2 Handling and storage of data and documents 
 
The investigator or his/her designee will document all data obtained during the registry on 
the individual eCRFs provided by the University of Rome “Tor Vergata” location PTV. 
Investigators will have access to the DMS, and will receive their own username and 
password. Only data from their own center is accessible for investigators. Data managers 
from the University of Rome “Tor Vergata” location PTV will have full access to all data 
collected during this registry, for purposes of monitoring data collection and analyzing the 
data. The University of Rome “Tor Vergata”, will maintain the electronic database. The 
DMS is compliant with GCP, GDPR, and 21 CRF 11. It is located in a secure and fully 
certified datacenter. The DMS is certified to store medical data (NEN7510, ISO 9001, 
14001 and 27001:2013). Patient data will be entered encoded; the key to coded 
information is held at each study center for its own patients and is the responsibility of the 
local Investigator. Handling of personal data by the DMS is in total compliance with the 
General Data Protection Regulation (GDPR) – Regulation (EU) 2016/679. 
 
 
The number of centers participating in this registry is not limited, although all sites must 
receive approval of the University of Rome “Tor Vergata” location PTV and Steering 
Committee before commencing the data collection in this registry. Prior to receiving 
approval of University of Rome “Tor Vergata” location PTV, an IRB approval / waiver shall 
be provided when mandatory according to local regulations. Sites may be proposed by 
the members of the Steering Committee or on recommendation from third parties. 
 
 
Data handling and safety is arranged in the regulatory document to which all participants 
to the registry have committed by signing an accession form. The regulatory document is 
in line with the GDPR. All participating centers will need to apply to the GDPR. 
 
 
Primarily, the participant that includes its data in the registry shall remain the owner of its 
data and the results arising from the registry shall belong to University of Rome “Tor 
Vergata” location PTV. 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
 
After a request to the Steering Committee and receiving authorization from the University 
of Rome “Tor Vergata” location PTV, study participant members can present data at 
relevant occasions. 
 
 
8.3 Monitoring and Quality Assurance 
 
University of Rome “Tor Vergata” location PTV, will perform monitoring of this registry. 
Data entered into the web-based DMS will be secured and checked for irregularities. In 
addition, the DMS provides detailed overview reports of inclusion and runs queries to 
check for inconsistencies in collected data, to ensure a reliable dataset. To minimize 
missing data, messages will be sent to investigators to encourage and remind them of 
entering data collected at follow-up time points. 
 
 
During the registry or once the registry has been completed, the Steering Committee and/or 
University of Rome “Tor Vergata” location PTV representatives may carry out an audit. The 
audit will focus on data source verification and critical values in the database. Regulatory 
bodies may also inspect the registry. If a regulatory authority contacts an investigator with a 
request for an inspection, the investigator must inform the University of Rome “Tor Vergata” 
location PTV immediately. 
 
 
8.4 Amendments 
 
Substantial amendments will be reviewed by Steering Committee for their opinion prior to 
implementation. 
 
 
8.5 Public disclosure and publication policy 
 
It is the intention of the registry to jointly publish the results. Based on contribution of 
participants, their scientific representatives will be involved in publications and according 
to their contribution included in the authors list. Each of the participants may send a 
request to the Steering Committee for a specific research topic to be investigated by the 
Coordinator. The Coordinator shall have a co-authorship position in all publications 
resulting from such requests. All acknowledgments shall be in accordance with the ICMJE 
guidelines for publication. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol: Registry FLA for Pca 
V1.2 - 9 July 2019 
 
 
 
9. REFERENCES 
 
1. Donaldson, Ian A., et al. "Focal therapy: patients, interventions, and outcomes—a 
 
report from a consensus meeting." European urology 67.4 (2015): 771-777. 
 
2. Mottet N, Bergh RCN Van Den, Vice-chair PC, Santis M De, Gillessen S, Govorov 
A, Grummet J, Henry AM, Lam TB, Mason MD, Kwast TH Van Der, Rouvière O, 
Wiegel T, Broeck GAT Van Den, Cumberbatch M, Fossati N, Gross T, Lardas M, 
Liew M, Moris L, Schoots IG, Willemse PM. EAU-ESUR-ESTRO-SIOG Guidelines 
on Prostate 
 
3. Patelli G, Ranieri A, Paganelli A, Mauri G, Pacella CM. Transperineal Laser 
Ablation for Percutaneous Treatment of Benign Prostatic Hyperplasia: A Feasibility 
Study. Cardiovasc Intervent Radiol 2017;40(9):1440–1446. PMID:28474112 
 
4. Walser, Eric, et al. "Focal Laser Ablation of Prostate Cancer: Results in 
120 Patients with Low-to Intermediate-Risk Disease." Journal of Vascular 
and Interventional Radiology30.3 (2019): 401-409. 
 
5. van Luijtelaar, A., et al. "Focal laser ablation as clinical treatment of prostate 
 
cancer: 
report from a Delphi consensus project." World Journal of 
 
Urology (2019): 1-7. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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