Neoplasms

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anticoagulants

All Drugs and Chemicals

Micronutrients

Edetic Acid

Pentetic Acid

Antidotes

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Iron

Iron Chelating Agents

Patients receive gadodiamide IV and undergo a diagnostic multiparametric endorectal MRI. Patients with lesions visible on the diagnostic multiparametric endorectal MRI undergo transrectal MRI-guided biopsy within 2 weeks of diagnostic multiparametric endorectal MRI. Patients then undergo TRUS-guided biopsy per standard clinical care approximately 2 weeks after transrectal MRI-guided biopsy.

Undergo diagnostic multiparametric endorectal MRI with gadodiamide contrast

3 Tesla Magnetic Resonance Imaging

Gadodiamide

Multiparametric Magnetic Resonance Imaging

Transrectal Biopsy

Ultrasound-Guided Prostate Biopsy

Fergus Coakley

This pilot clinical trial studies transrectal magnetic resonance imaging (MRI)-guided biopsy to see how well it works in identifying cancer in patients with suspected prostate cancer who are scheduled to undergo standard biopsy. Transrectal MRI-guided biopsy uses a thin needle inserted through the rectum into the prostate and takes a sample of tissue, guided by MRI. MRI uses magnets to take pictures of the prostate and may be able to identify cancer. Transrectal MRI-guided biopsy may be more accurate and cause patients less pain than standard ultrasound-guided biopsy. It is not yet known whether transrectal MRI-guided biopsy is more effective than ultrasound-guided biopsy in identifying prostate cancer.

PRIMARY OBJECTIVES:

I. To improve the treatment of patients with prostate cancer utilizing diagnostic multi-parametric magnetic resonance imaging (MRI) and MRI-guided prostate biopsy combined with molecular and clinical data to help determine the extent of prostate cancer and risk of disease progression.

II. To determine the relative accuracy of transrectal MRI-guided versus ultrasound-guided biopsy for the diagnosis of prostate cancer in patients with an appropriate dominant target lesion at multiparametric MRI, using pooled cancer diagnoses by either MRI-guided or ultrasound-guided biopsy as the reference standard.

III. To determine the proportion of positive transrectal MRI-guided biopsies that demonstrate a higher Gleason score than contemporaneous transrectal ultrasound guided biopsy.

IV. To determine the management impact of transrectal MRI-targeted biopsy results as compared to transrectal ultrasound (TRUS)-guided systematic biopsy results.

OUTLINE:

Patients receive gadodiamide intravenously (IV) and undergo a diagnostic multiparametric endorectal MRI. Patients with lesions visible on the diagnostic multiparametric endorectal MRI undergo transrectal MRI-guided biopsy within 2 weeks of diagnostic multiparametric endorectal MRI. Patients then undergo TRUS-guided biopsy per standard clinical care approximately 2 weeks after transrectal MRI-guided biopsy.

Transrectal MRI-Guided Biopsy in Identifying Cancer in Patients With Suspected Prostate Cancer

Pilot Study of Transrectal Multiparametric MRI-Guided Biopsy: Role in Prostate Cancer Evaluation

The proportion of MRI-guided biopsies that demonstrate a higher Gleason score than contemporaneous TRUS guided biopsy for all patients diagnosed of prostate cancer based on the reference standard will be estimated. McNemar's test will be used to assess whether the MRI-guided biopsies are more likely to yield a higher Gleason score compared with TRUS guided biopsy. Simple logistic regression model will be used to assess the association between the higher Gleason score and patient characteristics and/or clinical information for patients diagnosed of prostate cancer.

The presence of cancer on either biopsy or absence of cancer on both will be used as the reference standard. For comparison of the two methods, the 2X2 matched sample tables will be presented, and the difference in sensitivity estimated. The relative accuracy of MRI- versus TRUS-guided biopsy will be compared using McNemar's test. To explore potential associations between the accuracy of each method with patient characteristics and/or clinical information, a binary endpoint will be created to reflect agreement between each method and the reference standard.

Medical Research Foundation, Oregon

National Cancer Institute (NCI)

OHSU Knight Cancer Institute

Professor and Chair

Patients receive gadodiamide IV and undergo a diagnostic multiparametric endorectal MRI. Patients with lesions visible on the diagnostic multiparametric endorectal MRI undergo transrectal MRI-guided biopsy within 2 weeks of diagnostic multiparametric endorectal MRI. Patients then undergo TRUS-guided biopsy per standard clinical care approximately 2 weeks after transrectal MRI-guided biopsy.

3 Tesla Magnetic Resonance Imaging: Undergo diagnostic multiparametric endorectal MRI with gadodiamide contrast

Gadodiamide: Given IV

Multiparametric Magnetic Resonance Imaging: Undergo diagnostic multiparametric endorectal MRI with gadodiamide contrast

Transrectal Biopsy: Undergo transrectal MRI-guided biopsy

Ultrasound-Guided Prostate Biopsy: Undergo TRUS-guided biopsy

Diagnostic (MRI, MRI-guided Biopsy, TRUS-guided Biopsy)

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Since recruitment was very low and funding did not materialize, the study was closed early and insufficient data was collected to analyze and report the outcomes.

Fegus Coakley

Due to low enrollment, insufficient data was collected to report this outcome

Proportion of MRI-guided Biopsies That Demonstrate a Higher Gleason Score Than Contemporaneous TRUS Guided Biopsy

Sensitivity of MRI-guided Biopsy

Sensitivity of TRUS-guided Biopsy

Overall Study

Infections

Symptoms and General Pathology

Communicable Diseases

Central Nervous System Depressants

Anesthetics

Anesthetics, Local

LATP prostate biopsy performed with an average of 12 biopsy cores in 6 sectors depending on prostate size, plus typically 4 target cores per MRI lesion, using an ultrasound probe-mounted LATP needle guidance device (e.g. the "Precision-Point" access system, or BK UA1232, or any other which is used in a virtually identical fashion).

TRUS prostate biopsy performed according to each hospital's standard practice, with an average of 12 biopsy cores, in two sectors with additional target pots (typically 4 target cores per MRI lesion).

Prostate biopsy via either the Transrectal route (comparator) or Transperineal route (experimental), each under local anaesthetic.

Prostate biopsy

Roxanne Williams

Richard Bryant, MBChB, PhD

Alastair Lamb, MBChB, PhD

Richard Bryant

Alastair Lamb

The TRANSLATE randomised controlled trial aims to evaluate local anaesthetic transperineal biopsy (LATP) versus transrectal ultrasound-guided (TRUS) prostate biopsy, in the evaluation of previously biopsy-naive men being investigated for clinically significant prostate cancer (on the basis of an elevated age-specific PSA, or abnormal digital rectal examination, or MRI-visible lesion). Men under investigation for possible prostate cancer and recruited to TRANSLATE will be randomised to receive either an LATP or TRUS prostate biopsy, with the primary outcome measure being detection of clinically significant prostate cancer (defined as any Gleason pattern 4 disease, i.e. any Gleason Grade Group \>=2 disease). Secondary outcome measures include infection, other complications, tolerability, rate of re-biopsy, detection of clinically insignificant prostate cancer, and a full health economics evaluation.

100,000 men each year in the United Kingdom are referred for investigation for possible prostate cancer based on an abnormal digital rectal examination of the prostate and/or an elevated age-specific PSA blood test. These men may be offered a pre-biopsy MRI scan, followed by a prostate biopsy. Prostate biopsies have typically been taken via an ultrasound-guided transrectal approach (TRUS) under local anaesthetic in the clinic for several decades. However, local anaesthetic transperineal biopsy (LATP) has been pioneered in recent years, in order to sample the prostate gland via the perineum in the clinic, with the potential advantage that the transperineal approach to sampling reduces the risk of serious infection, and improves the sampling of the prostate gland (thus increasing the cancer detection), whilst avoiding the need for general anaesthetic in the operating theatre (as was the case for historical template prostate biopsies).

The way in which urologists take biopsies for possible prostate has started to vary across the United Kingdom; however, no level 1 evidence exists as to which method is best - both in terms of detecting clinically significant prostate cancer, and in terms of the occurrence of serious infection and other common side-effects of the biopsy process, along with patient tolerability, re-biopsy rate, and cost-effectiveness.

The TRANSLATE study aims to recruit 1042 men from at least 9 large Urology departments from United Kingdom Hospitals. These men will be under investigation for possible prostate cancer, and will not have received a prostate biopsy previously.

All men eligible for the study will have had a pre-biopsy MRI scan as part of the investigation for possible prostate cancer. After obtaining informed consent they will be randomised to either a TRUS biopsy or an LATP biopsy. Following the biopsy procedure, the study team will follow up the men in order to determine the rate of detection of clinically significant prostate cancer (primary outcome) in each biopsy group. The study team will also gather information (as secondary outcomes) on the occurrence of any post biopsy infections, and other patient reported biopsy-related complications such as bleeding, bruising, pain, and loss of erections and sexual function. Additionally, the study team will record any subsequent prostate biopsy procedures, which might be recommended if the first prostate biopsy has produced a possible 'false negative' result, where clinicians have concerns that the prostate biopsy result is inconsistent with the pre-biopsy MRI scan result and where there are concerns that a 'clinically significant' prostate cancer may have been under-detected. Data will be collected before the biopsy (baseline), immediately after the biopsy, and then at 7 days, 35 days and 4 months following the biopsy.

The total length of the study is 31 months (to include trial setup phase, recruitment phase, data analysis and write-up of reports and publications). Recruitment of patients will last for 15 months. There will be a formal 'stop/go' review at the end of month 12 (i.e. after a full 6 months of recruitment) in order to ensure that a minimum of 140 patients has been randomised, and that at least 4 centres have been opened to recruitment. If the study team meets the 'stop/go' recruitment target, the trial will continue to recruit for a further 9 months. Data from all patients recruited in the 15 month period will be included in the final analysis.

The TRANSLATE Trial

A Randomised Controlled Trial Comparing TRANSrectal Biopsy Versus Local Anaethetic Transperineal Biopsy in Evaluation (TRANSLATE) of Men With Potential Clinically Significant Prostate Cancer

Clinically significant prostate cancer (as defined by the presence of Gleason Grade Group ≥2 prostate cancer, i.e. any Gleason pattern ≥4 disease).

Post-biopsy infection - patient questionnaire reporting.

Histology reporting of grading of biopsy samples as per local reporting practices.

National Institute for Health Research, United Kingdom

University of Oxford

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
Transrectal MRI-Guided Biopsy in Identifying Cancer in Patients With Suspected Prostate Cancer	NCT02501759	Health Status U... Prostate Carcin...	3 Tesla Magneti... Gadodiamide Multiparametric... Transrectal Bio... Ultrasound-Guid...	-	OHSU Knight Cancer Institute
The TRANSLATE Trial	NCT05179694	Prostate Cancer	Prostate biopsy	18 Years -	University of Oxford
US/MRI Fusion Local Anestesia TransPerineal Prostate Biopsies for Detection of Prostate Cancer	NCT04797078	Prostate Cancer	Transperineal b... Transrectal bio...	18 Years -	Karolinska Institutet

Spots Global Cancer Trial Database for transrectal biopsy