Transperineal Targeted Focal Laser Ablation of Localized Intermediate Risk Prostatic Adenocarcinoma (Pilot Study)
Conditions: Prostate Cancer, Laser
Sponsor: Ain Shams University

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 1 
PROTOCOL OF A THESIS FOR PARTIAL FULFILLMENT OF M.D. 
DEGREE IN UROLOGY 
 
Title of the Protocol: Transperineal Targeted Focal Laser Ablation of 
Localized Intermediate Risk Prostatic Adenocarcinoma (Pilot Study) 
 
Postgraduate Student: Khaled Adel Ahmed Ahmed 
Degree: M.B.B.Ch., MSc, Faculty of Medicine – Ain Shams University– Egypt. 
 
DIRECTOR:  
Prof. Dr. Hassan Sayed Shaker 
Academic Position:  
Professor 
Department:  
Urology 
 
Faculty of Medicine, Ain Shams University 
 
DIRECTOR:  
Assoc. Prof. Dr. Haytham Mohamed Nasser 
Academic Position:  
Associate Professor 
Department:  
Diagnostic & Interventional Radiology and Molecular Imaging 
 
Faculty of Medicine, Ain Shams University 
 
DIRECTOR:  
Assoc. Prof. Dr. Aliaa Sayed Sheha 
Academic Position:  
Associate Professor 
Department:  
Diagnostic & Interventional Radiology and Molecular Imaging 
 
Faculty of Medicine, Ain Shams University 
 
DIRECTOR:  
Assoc. Prof. Dr. Waleed Elsayed Mohamed Mousa 
Academic Position:  
Associate Professor 
Department:  
Urology 
 
Faculty of Medicine, Ain Shams University 
 
DIRECTOR:  
Dr. Haitham Mohamed Ali Mohameden 
Academic Position:  
Lecturer 
Department:  
Urology 
 
Faculty of Medicine, Ain Shams University 
 
 
Faculty of medicine 
Ain Shams University 
2024 
 
 
 
 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 2 
1.INTRODUCTION/ REVIEW 
Prostate cancer (PCa) is the second most common neoplasm diagnosed in men 
with an estimated 1.4 million diagnoses and 375,000 deaths worldwide in 2020 [1]. 
For localized prostate cancer (PCa), active surveillance (AS) or whole gland 
treatment (ie, radical prostatectomy [RP] and radiotherapy) are considered standard 
treatment options. Unfortunately, treatment-related morbidity is high. [2] 
The ProtecT trial showed urinary incontinence rates of 3% and 20% and 
erectile dysfunction rates of 66% and 79% for radiotherapy and radical 
prostatectomy, respectively [2]. Radiotherapy can also cause rectal problems with a 
small increased risk of radiotherapy-induced secondary malignancy. [3] 
Consequently, over the past few years, there has been a notable escalation in 
scholarly attention towards the implementation of focal therapeutic interventions for 
patients diagnosed with low- and intermediate-risk prostate cancer (PCa). 
This tissue-preserving strategy has at its core the reduction of treatment-
related toxicity by minimizing damage caused to the prostate and adjacent structures 
while attempting to retain the benefits of treating cancer. [4] 
The rationale of focal therapy (FT) is based on the theory that the largest 
lesion with the highest grade, the so-called “index lesion,” determines the risk of 
metastases and thus the patient’s prognosis [5, 6]. 
FT involves ablating only the index lesion, thereby minimizing damage to 
collateral tissue such as neurovascular bundles, external urinary sphincter, bladder 
neck and rectum. [4] 
Over the past few years, different types of energy sources in FT have been 
studied. These consist of high-intensity focused ultrasound (HIFU), irreversible 
electroporation (IRE), cryotherapy, photodynamic 
therapy (PDT), 
focal 
laser 
ablation (FLA) or laser interstitial thermotherapy, radiofrequency ablation (RFA), 
and focal brachytherapy.  [7] 
According to the European Association of Urology (EAU), low-risk and 
intermediate-risk patients may undergo local procedures using HIFU or cryotherapy 
within clinical trials or registries, with the aim of achieving long-term cancer control 
and reducing morbidity associated with surgery and radiation therapy [8]. 
Many groups have published limited data on outcomes following in-bore 
MRI-guided focal therapy, and many others are actively engaged or considering 
prospective comparative effectiveness research in this area. 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 3 
Our primary objectives encompasses a thorough evaluation of the short-term 
oncological & functional outcomes of MRI-US or PSMA PET/CT-U/S fusion-
guided focal laser ablation (FLA) for the treatment of a small, localized, 
intermediate-risk prostate cancer. 
Concurrently, our secondary aim involves an assessment of the utility of 
multiparametric magnetic resonance imaging (mpMRI) as a diagnostic pre-treatment 
tool and during the post-treatment follow-up to examine the morphostructural 
alterations in the prostate gland resulting from FLA. Additionally, we aim to assess 
its reproducibility in determining the response to FLA therapy, correlating these 
findings with biopsy results, with the ultimate objective of establishing its predictive 
diagnostic value in identifying residual or recurring tumors. 
 
2.AIM/ OBJECTIVES 
To assess the effectiveness of MRI-US or PSMA PET/CT-U/S fusion-guided 
focal laser ablation (FLA) for the treatment of a localized, intermediate-risk prostate 
cancer in terms of short-term oncological & functional outcomes. 
 
3.METHODOLOGY: 
Patients and Methods/ Subjects and Methods/ Material and Methods 
 Type of Study: Retrospective Observational Pilot study  
 Study Setting: El-Demerdash University Hospital & Shaker Hospital. 
 Study Period: 12 months. 
 Sample Size: based on the rarity of cases in this study and the expensive cost of 
treatment, also this study is a pilot study. This protocol is exempted from sample 
size calculation. (No. of the patients will be 30)                                                         
 Study Population: Males with localized, intermediate risk prostatic adenocarcinoma 
Self-funded study (the researcher himself will pay for the data collection). 
The patients will not pay any fees. 
 Inclusion Criteria: 
o Male 
o Over 45 years old 
o Prostate cancer visible on mpMRI or PSMA PET/CT and positive in the 
targeted biopsy. 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 4 
o Gleason score 7 (ISUP grade 2/3) 
o PSA 10-20 ng/mL 
o Clinical stage  T2b 
o Refusing radical prostatectomy. 
 Exclusion Criteria: 
o Prostate cancer invisible on mpMRI or PSMA PET/CT but positive in the 
systematic biopsies. 
o Presence of >2 MRI-visible lesions and positive in the biopsies. 
o Extracapsular extension 
o Seminal vesicle invasion 
o Presence of metastases detected by imaging 
o Gleason Score > 7 
o Clinical stage > T2b 
o PSA > 20 ng/mL 
o Acute urinary tract infection (UTI) 
o Severe lower urinary tract symptoms defined as an IPSS >20 
o Severe coagulation disorders 
o Inadequate compliance 
o Contraindications to MRI 
o Paramagnetic contrast agent allergy 
o Acute and/or chronic renal failure 
 Ethical Considerations: Approval will be obtained from the ethical committee at 
Ain Shams University before starting the research and all patients will consent to 
be included in this study after explanation of the study procedures and the follow 
up course. 
 Study Procedures: 
The pre-procedural evaluation consisted of complete blood count, coagulation 
profile, urine examination and urine culture, and evaluation of post-voiding residue 
and uroflowmetry. 
As the procedure of FLA is guided by MRI-US or PSMA PET/CT-U/S fusion 
images, a 3T mp MRI scan or PSMA PET/CT scan is recommended for each patient at 
Time 0. 
On Siemens 3T MAGNETOM Skyra scanner, multiple MRI sequences will be 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 5 
taken including T1, T2WI, DWI, ADC and STIR axial, coronal and sagittal images. 
Injection of 2-4 ml/s of gadolinium and then post contrast dynamic imaging will 
be taken. 
Malignant lesions will appear low signal at T2WI in comparison to the high signal 
intensity of the peripheral zone with restricted DWI and post gadolinium contrast 
enhancement. 
The FLA is performed by a joint team of an expert interventional radiologist 
and an expert urologist on prostate MRI-US or PSMA PET/CT-U/S procedures, in a 
Day-Hospital setting, in a radiological interventional room or an OR. 
The patient is placed in the lithotomy position, and Ciprofloxacin 500 mg is 
administered as antibiotic prophylaxis. The biolitec® LEONARDO® DUAL 45 
Diode Laser System operating at 860 nm provides energy for the ablation. 
The mpMRI data are loaded to the US system (Canon Aplio a550) via the 
DICOM network or a DVD and the live US image is linked with the MR image by 
Smart Fusion. 
Under general or spinal anesthesia, thin needles (14 Gauge) are inserted 
transperineally under real-time US guidance fused with MRI or PSMA PET/CT. One 
to five needles are used depending on the lesion size and configuration because the 
multi-fiber approach can extend the coagulation area. 
          The laser light is conveyed from the source to the target through flexible, 
small-caliber (360 μm), flat-tipped quartz optical fibers. Multiple overlapping 
ablations are performed in order to assure complete coverage of the target. 
The laser fiber protrudes 5 mm from the needle tip. The pull-back technique 
consists of pulling back the introducer by 1 cm and performing a second illumination 
to increase the length of the ablation area. 
The laser energy is released in pulsed mode (intermittently in a series of pulses 
rather than continuously – 0.8 seconds on & 0.4 seconds off), with a power of 15 
Watts and is activated for for an average of 2 minutes (100 pulses) per ablation zone. 
The laser therapy is performed entirely under US guidance fused with MRI or 
PSMA PET/CT for the real-time monitoring of the correct positioning of applicators 
and the extension of the area of damage. 
At the end of the procedure, all patients are observed for a minimum period of 
2 h. 
An oral NSAID as anti-edema therapy is prescribed. 
Patients are discharged with antibiotic therapy for 14 days, given pain-relief 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 6 
drugs if needed. 
A copy of the patients’ files will be anonymously given to the researcher. 
Follow-up with clinical evaluation performed by monthly PSA measurement 
until it reaches its nadir (fixed value for 2 months) and every 3 months thereafter. 
Repeat mpMRI is done for assessment of tissue changes as well as residual or 
recurrent disease after 10 days, then after 3 months, after 6 months then every 6 
months thereafter. The IPSS and IIEF-5 questionnaires are submitted at 3, 6, 12 
months. 
Systematic and target MRI/US fusion-guided prostate biopsies are performed 
after 12 months or if PSA increases > 2 ng/mL, nadir PSA doubled or new suspicious 
lesions in mpMRI. 
Failed cases are offered a further session of focal therapy if the lesion is still 
suitable for FLA. Radical therapy is also offered according to patient preference, or in 
cases of increasing volume or stage of disease or progression to high grade disease. 
Treatment success is operationally defined as the absence of contrast-
enhancement in MRI examinations conducted during the follow-up period, in 
conjunction with a negative target biopsy at the conclusion of the 12-month period and 
evaluation of serum PSA. 
 
4.REFERENCES 
1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, 
A., & Bray, F. (2021): Global cancer statistics 2020: GLOBOCAN estimates of 
incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer 
journal for clinicians, 71(3): 209-249. 
2. Donovan, J. L., Hamdy, F. C., Lane, J. A., Mason, M., Metcalfe, C., Walsh, E., & 
Neal, D. E. (2016): Patient-reported outcomes after monitoring, surgery, or radiotherapy 
for prostate cancer. New England Journal of Medicine, 375(15): 1425-1437. 
3. Hamdy, F. C., Donovan, J. L., Lane, J. A., Mason, M., Metcalfe, C., Holding, 
P., ... & Neal, D. E. (2016): 10-year outcomes after monitoring, surgery, or 
radiotherapy 
for 
localized 
prostate 
cancer. New 
England 
Journal 
of 
Medicine, 375(15): 1415-1424. 
4. Lindner, U., Trachtenberg, J., & Lawrentschuk, N. (2010): Focal therapy in 
prostate cancer: modalities, findings and future considerations. Nature Reviews 
Urology, 7(10): 562-571. 
5. Eggener, S., Salomon, G., Scardino, P. T., De la Rosette, J., Polascik, T. J., & 
Brewster, S. (2010): Focal therapy for prostate cancer: possibilities and 

  
 
 
 
 
 
 
 
  
 
M.D. Thesis protocol /MFA/ISRO/Faculty Of Medicine/ASUPage 7 
limitations. European urology, 58(1): 57-64. 
6. Ahmed, H. U. (2009): The index lesion and the origin of prostate cancer. New 
England Journal of Medicine, 361(17): 1704-1706. 
7. Valerio, M., Cerantola, Y., Eggener, S. E., Lepor, H., Polascik, T. J., Villers, 
A., & Emberton, M. (2017): New and established technology in focal ablation of 
the prostate: a systematic review. European urology, 71(1): 17-34. 
8. Mottet, N., van den Bergh, R. C., Briers, E., Van den Broeck, T., 
Cumberbatch, M. G., De Santis, M., ... & Cornford, P. (2021): EAU-EANM-
ESTRO-ESUR-SIOG guidelines on prostate cancer—2020 update. Part 1: 
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urology, 79(2): 243-262.