Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All patients recruited to the study (this arm) will have an additional transrectal ultrasound whilst already under GA for TP biopsy.

Additional transrectal ultrasound whilst already under GA for transperineal biopsy.

Transrectal ultrasound scan of prostate

David Thurtle

Through this study the investigators seek to build up a repository of prostate ultrasonography videos and prostate MRI scans to enable research into novel anatomical registration techniques. These data will facilitate the development of improved technology that enables targeting of tumours seen on MRI using free-hand biopsy techniques, without the need for a gantry or overlaid perineal grid.

The purpose of this study is to explore whether mathematical and computational modelling techniques can be used to enable anatomical based real-time image registration for guiding prostate biopsies. This would lead to the ability to perform free-hand trans-perineal biopsy without the need for supporting gantries or a biopsy grid placed over the perineum. This will significantly decrease costs of trans-perineal biopsy, reduce the number of puncture sites through the perineal skin - reducing pain and bleeding - and reduce the procedure time. Alongside locally developed local-anaesthetic transperineal biopsy techniques it will allow targeted biopsy to be taken in the outpatient setting, improving patient convenience, and helping health services to meet growing demands on targeted biopsies.

The investigators aim to create a new method of mapping the prostate using free-hand ultrasound, without any additional physical equipment. This may require collaborations with approved International groups with particular skills in relevant mathematical or engineering techniques.

Capture of Prostatic Trans-rectal Ultrasound Scans for Research

Capture of Prostatic Trans-rectal Ultrasound Scans for Research Into Improved Targeted Biopsy Techniques (CAPTURE)

Ultrasound images and videos of the prostate will be captured to measure the length, width and depth of the prostate on ultrasound. The measurements will be in millimeters (mm). This will be taken at a single time-point at the time of general anaesthesia for transperineal biopsy.

Ultrasound images and videos of the prostate will be captured to assess prostate location relative to surrounding structures. Specifically this will mean measuring the distance from the anal verge to the prostate. Unit of measurment is millimeters (mm). This will be taken at a single time-point at the time of general anaesthesia for transperineal biopsy.

University of Cambridge

Cambridge University Hospitals NHS Foundation Trust

Clinical Research Associate and Honorary Urology Registrar

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

MRI prostate with contrast, followed by MRI-guided biopsy under local anaesthesia only if MRI show suspicious lesion. Men with non-suspicious MRI will not receive a biopsy.

24-core Systematic transperineal prostate biopsy under local anaesthesia

Multiparametric MRI prostates in the MRI arm will be performed using 1.5 or 3.0 Tesla scanner with a pelvic phased array coil and contrast injection. T2-weighted, diffusion weighted and dynamic contrast enhanced scans will be included and the reporting of MRI finding will be done according to PI-RADS (Prostate Imaging-Reporting and Data Systems) v2.1 recommendations. MRI-guided targeted biopsy will be performed by Urologists experienced in MRI-guided biopsy for men with PI-RADS score 3-5.

MRI and MRI-guided prostate biopsy

Transperineal 24-core biopsy using a free-hand technique under local anaesthesia will be performed under transrectal ultrasound guidance for men in this arm

TP-arm Systematic biopsy

Peter Ka-Fung CHIU, FRCS, PhD

Clarence LEUNG, FRCS

Wilson Hoi-Chak CHAN, FRCS

Chun Him Francis WONG, FRCS

Ka Fung Peter CHIU, FRCS, PhD

Chi-Ho Ip, FRCS

Trevor Churk-Fai Li, FRCS

Wayne P LAM, FRCS

Lee-Fung LEE, FRCS

This is a randomized controlled trial to evaluate the detection of clinically significant prostate cancer (csPCa) by MRI-targeted approach (MRI-arm) versus 24-core transperineal (TP) systematic biopsy (TP-arm). Clinically significant prostate cancer (csPCa) is defined as ISUP (International Society of Urogenital Pathology) Grade group ≥2 prostate cancer. Patients with elevated PSA 4-20 ng/mL with or without abnormal digital rectal examination (DRE) will be randomized in a 1:1 manner to MRI-arm or TP-arm. In the MRI-arm, multiparametric MRI prostate will be performed for each subject. MRI prostate is considered abnormal if PI-RADS (Prostate Imaging-Reporting and Data System, version 2.1) score is 3, 4 or 5. For subjects in MRI-arm with abnormal MRI, MRI-targeted biopsy will be performed, followed by 12-core systematic transperineal biopsy (sparing MRI-target). For subjects in MRI-arm with normal MRI, no biopsy is performed. For subjects in TP-arm, 24-core systematic transperineal biopsy will be performed without MRI guidance. The study flowchart is provided in Figure 1. The detection rates of csPCa will be compared between MRI-targeted biopsy plus 12-core systematic biopsy (in MRI-arm) versus TP-arm. The study hypothesis is MRI-guided prostate biopsy with 12-core systematic biopsy is superior to 24-core transperineal systematic biopsy in detection of csPCa.

The current study is a randomized controlled trial using a superiority design with the subjects randomized in 1:1 manner to either MRI-arm or TP-arm. In the MRI-arm, multiparametric MRI is performed for all subjects. If MRI is abnormal (PI-RADS score 3-5), 3-4 core targeted followed by 12-core systematic transperineal biopsies under local anaesthesia will be performed. If MRI is normal, no biopsy is performed. A 12-core systematic biopsy is also included in MRI-targeted biopsy as it has been shown in the Trio study that adding systematic biopsy increased the detection of csPCa.

In the TP-arm, no MRI will be performed, and all subjects will receive 24-core transperineal prostate biopsy under local anaesthesia. Patient will be followed up in clinic about 30 days after biopsy to review pathology result and complication.

Randomized controlled trial, 1:1 allocation

Extended Systematic Versus Mri-Assisted pRostate Transperineal Biopsy

A Randomized Controlled Trial Comparing Magnetic Resonance Imaging (MRI)-Targeted Biopsy and Extended Transperineal Systematic Biopsy for Detection of Clinically Significant Prostate Cancer: the SMART Trial

ISUP Grade 2 or above prostate cancer diagnosed on biopsy

ISUP Grade 1-5, the higher grade the higher risk.

The number of patients in MRI arm with normal MRI

The severity of Adverse event is grade by Clavien-Dindo classification

Chinese University of Hong Kong

Associate Professor

Anti-Arrhythmia Agents

Channel Blockers

Anti-Infective Agents

Dermatologic Agents

Lidocaine

Anti-Bacterial Agents

Chlorhexidine

Chlorhexidine gluconate

Antibiotics, Antitubercular

1. Transrectal approach, patient in left lateral position, local anestesia 10ml lidocaine 1% at prostate base laterally and apex if indicated.
2. MRI-ultrasound fusion-guided biopsies with 4 biopsy cores per lesion, where clinically indicated. 18G biopsy needle.
3. Standard 12-core template for systematic biopsies. 18G biopsy needle.
4. Antibiotic prophylaxis with 750mg ciprofloxaicin, single dose p.o.

Men randomized to the experimental arm undergoes free-hand targeted transperineal fusion biopsies as defined below.

1. Patient is placed supine in the lithotomy-position. The perineal area is prepared with chlorhexidine 0,5ml/ml.
2. Ropivacain 7,5mg/ml is used as an anesthetic agent. Up to 40ml's (equivalent to 300mg) can be used to anestitize the skin, caudal and cranial part of the urogenital diaphragm and periprostatic tissue.
3. Free-hand MRI-ultrasound fusion-guided biopsies with at least 4 biopsy cores per lesion. Coaxial technique with 18G biopsy needle.
4. 10-12 Systematic biopsies according to the modified Barzell 12-core template.
5. No antibiotic profylaxis unless warranted by immunosuppression, previous sepsis or urinary tract infection.

Transperineal free hand MRI-US fusion prostate biopsy

Transperineal biopsy

Transrectal MRI-US fusion prostate biopsy

Transrectal biopsy

Tobias Nordström, PhD

We are conducting a randomised trial comparing outcomes of transperineal prostate biopsies under free-hand software assisted MRI/US fusion with transrectal biopsy guide software assisted MRI/US fusion. Primary outcome is the detection of clinically significant prostate cancer. Secondary outcomes is rate of complications including infection and sepsis, as well as feasibility and patient tolerability.

Prostate cancer is a leading cause of cancer death among men in the Western world. Early detection of prostate cancer has been shown to decrease mortality. When a test for prostate cancer yields an elevated risk of prostate cancer, tissue sampling from the prostate is warranted. The common practice is to acquire these biopsies has been via transrectal biopsies under ultrasound guidance (TRUL-biopsies). A low estimate of the risk of hospital-requiring infection is 5%, yielding unnecessary and costly sepsis cases.

In addition to suffering and loss of production, as well as healthcare costs, in a material from Taiwan, the mortality risk of biopsy-induced sepsis has been estimated at 0.13%. In a publication from Norway, it is estimated that infection complications from tissue sampling of the prostate cause 10 deaths per year (population 5 million).

Previous international studies show that the risk of infection with bacteria from the gut can be completely eliminated by taking the tissue samples through the skin of the perineum, transperineal biopsies (TPb), with guidance from transrectal ultrasound. This method is well established for systematic biopsies and has been proven safe in large series.

Studies have showed how multiparametric magnetic-resonance imaging (mpMRI) of the prostate accurately can identify lesions harboring clinically significant prostate cancer (csPC, defined as ISUP Gleason Group (GG) ≥ 2)3. Prostate MRI reading and reporting according to the PI-RADS protocol is widely accepted and recommended.

The image material from the MRI can be used to produce maps of the prostate used for tissue sampling of suspected areas. This is referred to as MRI/ultrasound fusion biopsy, or targeted biopsies (TBx). Regions of interest are marked as Lesions. Several studies have shown improved cancer detection using MRI and fusion targeted biopsies in clinical-practice cohorts 5,6 78 MRI/ultrasound fusion biopsies can be performed in a variety of ways, where software assisted transrectal biopsies has gained the most attention during the last few years, earning to development of equipment more readily available to the urologist as well as a rise in the quantity and quality of prostate MRI's.

The combination of transperineal prostate biopsies and targeted biopsies can be done with a rigid system of stepper and brachy-grid guiding. Recently, several systems for free-hand transperineal biopsies have been introduced, but data and recommendations on biopsy strategies and accuracy is lacking. The detection rates of cancer has not been evaluated in In comparison with transrectal prostate biopsy, transperineal prostate biopsy has the advantage of better sampling from the anterior area of the prostate, an area that is technically more challenging to sample with the transrectal approach. Other advantages of the transperineal route is believed to be the low risk of infection, and no risk ofrectal bleeding. The main challenge associated with the transperineal method is patient discomfort and pain management.

US/MRI Fusion Local Anestesia TransPerineal Prostate Biopsies for Detection of Prostate Cancer

Prospective Randomized Controlled Study: Free-Hand Transperineal vs. Transrectal Systematic and Image Fusion Targeted Biopsies Under Local Anesthesia Comparing Rate of Significant Cancer Detection and Complication Rates

* Pain level assessed by visual analogue scale (VAS)
* Most painful part of procedure
* Assessed immediately following procedure, and at 30 days

Rate of radical surgery and functional outcomes after radical prostatectomy.

Detection of clinically significant prostate cancer (defined as any ISUP \>2). Per PIRADS grade group.

Rate of infectious complications (defined as treatment with antibiotics) within 30 days after intervention. Stratified on infections requiring hospitalization.

Any complication after intervention requiring hotspital admission within 30 days

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Capture of Prostatic Trans-rectal Ultrasound Scans for Research	NCT03321864	Prostate Cancer Prostate Neopla...	Transrectal ult...	18 Years - 100 Years	Cambridge University Hospitals NHS Foundation Trust
Extended Systematic Versus Mri-Assisted pRostate Transperineal Biopsy	NCT04685928	Prostate Cancer	MRI and MRI-gui... TP-arm Systemat...	18 Years -	Chinese University of Hong Kong
US/MRI Fusion Local Anestesia TransPerineal Prostate Biopsies for Detection of Prostate Cancer	NCT04797078	Prostate Cancer	Transperineal b... Transrectal bio...	18 Years -	Karolinska Institutet

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