Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Infections

Symptoms and General Pathology

Prostatic Neoplasms

Communicable Diseases

Patient will have a transperineal prostate biopsy.

Patient will have a transrectal prostate biopsy.

Puncture of 12 to 30 percutaneous prostate core biopsies through the perineum with a transrectal ultrasound probe guidance. The procedure would be performed with the Artemis (Eigen) device allowing topographic recording of the puncture and MRI / ultrasound image fusion in order to target the MRI suspected lesion.

Transperineal prostate biopsy

Patient would undergo 12 to 30 transrectal prostate core biopsies through the rectum with a transrectal ultrasound probe guidance. The procedure would be performed with the Artemis (Eigen) device allowing topographic recording of the puncture and MRI / ultrasound image fusion in order to target the MRI suspected lesion.

Transrectal prostate biopsy

Alexandre INGELS, MD

Retrospective reports from literature have shown a lower rate of infections for transperineal versus transrectal approach for prostate biopsies in the setting of prostate cancer suspicion.

The aim of this study would be to compare in a prospective randomized trial the rate of infection with transperineal versus transrectal approach.

Retrospective reports from literature have shown a lower rate of infections for the transperineal versus transrectal approach for prostate biopsies in the setting of prostate cancer suspicion.

Post-biopsy infection is becoming a more and more challenging situation due to the increase of incidence and development of antibiotic resistant germs.

The aim of this study would be to compare in a prospective randomized trial the rate of infection with transperineal vs transrectal approach.

Patient presenting an indication of prostate biopsy (PSA elevation, suspicious lesion at digital rectal, suspicious lesion on MRI) would be randomized 1:1 among transrectal vs transperineal biopsies.

Post-biopsy infection would be monitored by systemic urine analysis at one, two and four weeks after procedure and in case of clinical symptoms.

Patients who will have prostate biopsy will be randomized 1:1 among transperineal or transrecal approach

Perineal Versus Rectal Approach for Prostate Biopsy to Prevent Iatrogenic Infections

Urinary infection will be assessed based on urinanalysis : 10\^5 germs and 10\^4 leucocytes minimum)

Antibiotic resistant germ will be assessed on urinanalysis

Presence of complication will be assessed during phone interview with the patient

Institut Mutualiste Montsouris

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

biologic sample preservation procedure

laboratory biomarker analysis

study of socioeconomic and demographic variables

diffusion-weighted magnetic resonance imaging

dynamic contrast-enhanced magnetic resonance imaging

multiparametric magnetic resonance imaging

quality-of-life assessment

transperineal prostate biopsy

transrectal prostate biopsy

ultrasound-guided prostate biopsy

Mark Emberton, MD, FRCS, MBBS

RATIONALE: Diagnostic procedures, such as magnetic resonance imaging (MRI), may help find prostate cancer and learn the extent of disease.

PURPOSE: This clinical trial is studying the safety of MRI and to see how well it works in diagnosing prostate cancer.

OBJECTIVES:

* To determine the ability of multiparametric magnetic resonance imaging (MP-MRI) to identify men who can safely avoid unnecessary biopsy.
* To assess the ability of the MP-MRI-based diagnostic pathway to improve the rate of detection of clinically significant cancer as compared to transrectal ultrasound (TRUS) biopsy.
* To estimate the cost-effectiveness of an MP-MRI based diagnostic pathway.

OUTLINE: This is a multicenter study.

Patients undergo multiparametric magnetic resonance imaging (MRI) (T2-weighted imaging, diffusion-weighted MRI, and dynamic contrast-enhanced MRI) followed by template prostate mapping and transrectal ultrasound biopsy.

Some patients may undergo blood, urine, and tissue sample collection periodically for biomarker studies. Samples are banked for future research analysis.

Patients complete a quality-of-life questionnaire (EQ-5D) at baseline, during, and after completion of study. An economic analysis will be performed for cost-effectiveness.

After completion of study intervention, patients are followed up periodically.

MRI in Diagnosing Prostate Cancer

PROMIS - Prostate MRI Imaging Study - Evaluation of Multi-Parametric Magnetic Resonance Imaging in the Diagnosis and Characterization of Prostate Cancer

University College London Hospitals

Behaviors and Mental Disorders

Erectile Dysfunction

Urinary Incontinence

Enuresis

Nocturnal Enuresis

Urination Disorders

Urologic Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Lower Urinary Tract Symptoms

Urological Manifestations

Behavioral Symptoms

Elimination Disorders

Mental Disorders

Psychotic Disorders

Sexual Dysfunction, Physiological

Sexual Dysfunctions, Psychological

questionnaire administration

assessment of therapy complications

high-intensity focused ultrasound ablation

SITU Trials Unit

Hashim Uddinn Ahmed, MD, FRCS

RATIONALE: Prospective trials using hemi-ablation with high intensity focused ultrasound (HIFU) (Sonablate 500) have demonstrated feasibility, safety, and encouraging functional outcomes and early cancer control with 90% of men achieving trifecta status (no erectile dysfunction, leak-free pad-free continence, cancer control). However, these trials have involved small numbers of patients with men selected for good baseline function. A multi-centre prospective trial within a larger cohort of men that better represents the patient population with prostate cancer (external validity) is required.

Verification of a new therapy as favourable, or equivalent, in outcome to 'standard' care is ideally sought through comparison with another matched control group. Randomised controlled trials (RCTs) offer the best method for minimising systematic bias and revealing the true effect of an intervention or drug. However, RCTs involving treatments of localised prostate cancer have had a historically poor patient uptake, as the reference 'gold' standard of care is not known. In addition, RCTs are expensive to run and involve huge infra-structural support. A number of trials in the USA have been forced to close due to lack of recruitment. The ProStart trial in the UK has also had to close for the same reason. It has been acknowledged by the Food and Drug Agency in the USA that comparative randomized trials will be problematic in this area due to lack of physician and patient equipoise. A randomized trial may be feasible if a pragmatic design is adopted but prior to acceptance of such a design, the number of centres with expertise in this complex intervention (mp-MRI, TTPM, focal HIFU) will need to be increased.

Observational studies are a commonly used alternative to ascertain the effectiveness of a treatment. They are used to observe a treatment effect in a selected group of patients who are presumed to derive benefit from the treatment given. Although methodologically not as robust, and therefore prone to bias, they have some benefits over RCTs. The principal ones are those of enhanced external validity (many patients do not wished to be randomised and therefore refuse participation), and more rapid accrual compared to a randomised design. For this reasons, a single arm medium term follow-up cohort intervention study has been designed. At the time of writing the safety and tolerability aspects of focal therapy by HIFU are known as a result of the Phase I/II studies carried out at UCLH. The results have been presented and exist in the public domain in abstract form but have not yet been published (presented in tables above). These early studies were powered to detect a change in the proportion of men who could obtain an erection sufficient for penetration compared to their status prior to their treatment. The very low event rate for both erectile dysfunction and incontinence indicates that the 'proof of concept' has been demonstrated for focal therapy. Moreover, we can be relatively confident that, in expert hands, focal HIFU is safe. Therefore, a multi-centre study is now required involving a larger group of patients for the following reasons:

1. To evaluate medium term cancer control using histological parameters. Stage two of INDEX will evaluate conversion to radical and systemic therapies and link men to national databases to determine survival in 5 and 10 years.
2. To confirm that focal therapy can lead to low rates of genitourinary and rectal toxicity and minimal impact on quality of life within a large and more representative cohort of patients (greater precision around outcome measures).
3. To demonstrate that the skills (characterization through template prostate mapping and MRI as well as the treatment related skills) acquired by the team at UCLH are indeed transferable to other providers.
4. To calculate costs of care and to model potential cost-effectiveness in comparison to alternative therapies. If this single arm intervention study demonstrates acceptable outcomes to support the findings of the Phase I/II studies, it is anticipated that this preliminary study will lead onto a Phase III evaluation of focal therapy, prior to more widespread use of this technology.

Multi-Centre Prospective Single Arm Intervention Trial

Focal Therapy for Prostate Cancer Using HIFU

A Multi-Center Prospective Single Arm Intervention Trial Evaluating Focal Therapy Using High Intensity Focused Ultrasound (Sonablate 500) for Localized Prostate Cancer

To determine the proportion of men converting to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer following focal therapy for localised prostate cancer using HIFU

The presence of severe erectile dysfunction at 12 months, as measured by the IIEF-5 questionnaire with or without the use of phosphodiesterase-5 inhibitors, in those with absence of severe erectile dysfunction at baseline

The presence of severe erectile dysfunction at 24 months, as measured by the IIEF-5 questionnaire with or without the use of phosphodiesterase-5 inhibitors, in those with absence of severe erectile dysfunction at baseline

Time to return of erectile function (absence of severe ED on IIEF-15 questionnaire)

Presence of urinary incontinence (any pad usage plus any leakage of urine) as determined by the UCLA-EPIC urinary continence questionnaire, at 12 months, in those men with no urinary incontinence at baseline

Presence of urinary incontinence (any pad usage plus any leakage of urine) as determined by the UCLA-EPIC urinary continence questionnaire, at 24 months, in those men with no urinary incontinence at baseline

Time to return of urinary continence (as determined by UCLA-EPIC Urinary domain questionnaire)

rate of loss of ejaculation (as determined by IIEF-15 questionnaire)

rate of loss of orgasm (as determined by IIEF-15 questionnaire)

rate of pain during intercourse (as determined by IIEF-15 questionnaire)

Need for phosphodiesterase-5 inhibitors to maintain erectile function sufficient for penetration up to 24 months

Grading of lower urinary tract symptoms as determined by IPSS scores

General and prostate health related quality of life measured using EQ-5D Quality of Life questionnaire

Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 12 months in those men with good baseline function

Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 24 months in those men with good baseline function

rate of secondary prostate cancer intervention (prostatectomy, radiotherapy, androgen ablation, whole-gland HIFU or cryosurgery)

risk factors for failure defined as a) presence of any cancer and b) clinically significant

biochemical (PSA) kinetics including determining the optimal biochemical definition of

To determine the costs of treatment and model potential cost effectiveness using comparative cancer control and functional outcomes at 5 years compared to other cohort trials involving the management of localized prostate cancer

To determine the costs of treatment and model potential cost effectiveness using comparative cancer control and functional outcomes at 10 years compared to other cohort trials involving the management of localized prostate cancer

University College, London

Prostatic Hyperplasia

Hyperplasia

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

The biopsy needed is inserted to the prostate through the perineal skin, with the assistance of an access system device known as PrecisionPoint. It utilises a single access needle cannula mounted directly on to the ultrasound probe, which acts as an access point traversing through the perineal skin. 4 - 5 cores are obtained from the anterior, mid and posterior zone of each side of the prostate.

The biopsy needle penetrates through the bowel (rectum) to the prostate to obtain 12 cores of prostate tissues from the lateral and medial base, midzone and apex of each side of the prostate (1 core each).

Samples of tissue are removed from the prostate for histopathological diagnosis of prostate cancer through the use of a needle with the assistance of transrectal ultrasound.

Prostate Biopsy

Research Assistant

Wayne Lam, MBBS(Lond)

Wayne Lam

Tranperineal prostate biopsy(TPB) and Transrectal prostate biopsy(TRUSB) are now both routine diagnosis methods of prostate cancer in Queen Mary Hospital. The TRUSB has been the most common way to sample prostate tissue for decades. The TPB has been employed as one of our routine diagnosis methods in early 2018. The aim of this study is to evaluate whether Tranperineal prostate biopsy using a noval transperineal access system under local anaesthesia is non-inferior to standard 12-cores Transrectal prostate biopsy in detecting prostate cancer (PCa), in patients with clinical suspicion of PCa with no prior prostate biopsy.

The incidence of prostate cancer (PCa) has increased considerably in recent years \[1, 2\]. The reported lifetime risk for men in Hong Kong to be diagnosed with PCa is 1 in 31 before the age of 75, and is currently the third commonest cancer Hong Kong men according to the Hong Kong Cancer Registry \[3\]. This highlights the importance of thorough and fundamentally a safe investigation technique to correctly identify patients with PCa. Such test should be able to sensitively detect PCa, and provide early diagnosis. Critically, such test is required to provide accurate disease risk stratification, which is absolutely crucial in guiding level of appropriate treatment is necessary in patients diagnosed with PCa.

According to recommendations from the National Institute for Health and Care Excellence (NICE) guidelines, current standard clinical practice considers histological diagnosis of PCa a necessity in majority of patients presented with localized disease who are eligible for treatment \[4\]. This, alongside with prostate specific antigen (PSA) level, digital rectal examination (DRE) findings, and increasingly the use of multi-parametric MRI (mpMRI) imaging, collectively allows risk stratification of PCa.

The current pathway to obtain prostate tissue for histological diagnosis of CaP is by transrectal ultrasound-guided systematic biopsy (TRUSB) of the prostate, usually following the detection of a raised serum PSA level and/or suspicious rectal examination findings. TRUSB has been the standard prostate tissue sampling technique for men suspected with PCa for over 30 years. It is an office-based procedure carried out under local anaesthesia (LA), with 10 to 12 biopsy cores directed towards the lateral peripheral zones of the prostate thought to harbour majority of cancers \[7\]. However, there are still various well-known cancer detection limitations and patient safety problems associated with TRUSB.

Firstly, a very significant portion of tumours are being missed with the TRUSB technique \[8\]. It has been well- known that over 30% of patients with low risk PCa on TRUSB have been found to harbour clinically significant PCa \[9\]. Many of these tumours missed on TRUSB are located in the anterior and apical regions of the prostate, which TRUSB is difficult to access, in particular in patients with a large prostate volume

Secondly, TRUSB requires the biopsy needle to penetrate through the bowel (rectum). This results in high risk of developing sepsis following biopsy, despite all patients undergoing the procedure being started on antibiotics prophylactically. This is a serious complication which can potentially be life-threatening. Our previous study has already demonstrated a high prevalence of fluoroquinolone-resistant and ESBL-producing rectal flora in our local population in Hong Kong \[10\]. The risk of developing post-biopsy sepsis in Hong Kong is high.

Transperineal prostate biopsy (TPB) has been developed to provide a more comprehensive biopsy method to improve cancer detection rate by directing biopsy cores through the perineal skin. Theoretically, TPB enables access to sample the entire prostate, in particular the anterior and apical regions which are not easily accessible through the standard TRUSB method. By sampling the prostate using biopsy needles directly inserted through the perineal skin rather than bowel, the risk of sepsis is reduced. However, this technique requires multiple needles traversing through the perineum, and requires to be carried out under general anaesthesia (GA). Another disadvantage is a stabilising stepping unit is required to provide a consistent alignment of the ultrasound probe against the prostate in order to carry out the biopsies. Such stabilising stepping units are costly.

A novel but simple transperineal access system device known as PrecisionPoint (Perineologic, Cumberland, MD, USA) has been developed to tackle the aforementioned limitations of TPB. This revolutionary device utilises a single access needle cannula mounted directly on to the ultrasound probe, which acts as an access point traversing through the perineal skin. This design minimises the number of needle punctures through the skin, enabling TPB to be carried out under LA. A stabilising stepping unit is not required with this technique. The device has gained the United States Food and Drug Administration (FDA) approval \[11\], and results from small contemporary series have already been published with very promising results in terms of cancer detection rate and safety \[12\].

TRUSB has a poor cancer detection rate and is associated with potentially fatal septic risk. TPB, if able to be carried out under LA as an office-based procedure, can potentially provide a better cancer detection rate with significantly reduced sepsis risk. It has fundamentally a very high potential to become the new gold standard in obtaining prostate tissue for histological diagnosis of PCa.

With an increasing number of men in Hong Kong with elevated serum PSA suspicion of PCa needing prostate biopsy, it is fundamental to carry out a study to determine the most effective, safe and tolerable prostate biopsy technique which fits with the clinical practice in Hong Kong.

Whether Transperineal Prostate Biopsy Under Local-anaesthesia Using a Transperineal-access System is Non-inferior to Standard Transrectal Biopsy to Detect Prostate Cancer in Biopsy-naïve Men

Randomized-controlled Trial: Whether Transperineal Prostate Biopsy Under Local-anaesthesia Using a Transperineal-access System is Non-inferior to Standard Transrectal Biopsy to Detect Prostate Cancer in Biopsy-naïve Men

Absolute differences in PCa detection rate will be calculated with 95% CIs. If lower bound of 97.5% CI for the difference in cancer detection rates of LA TP biopsy compared with TRUS biopsy is greater than -5%, then TP biopsy will be deemed non-inferior. If lower bound is greater than 0, TP will be deemed superior.

The pain score of the procedure reported by patient

International Prostate Symptom Score (I-PSS)

International Index of Erectile Function (IIEF)

Ca Prostate with Gleason score larger or equal to 3+4

Time from start of ultrasound probe insertion to probe removal

The cost of each diagnosis based on the equipment, manpower and medication

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Perineal Versus Rectal Approach for Prostate Biopsy to Prevent Iatrogenic Infections	NCT03496142	Prostate Cancer	Transperineal p... Transrectal pro...	18 Years -	Institut Mutualiste Montsouris
MRI in Diagnosing Prostate Cancer	NCT01292291	Prostate Cancer	biologic sample... laboratory biom... study of socioe... diffusion-weigh... dynamic contras... multiparametric... quality-of-life... transperineal p... transrectal pro... ultrasound-guid...	-	National Cancer Institute (NCI)
Focal Therapy for Prostate Cancer Using HIFU	NCT01194648	Male Erectile D... Prostate Cancer Therapy-related... Urinary Inconti...	questionnaire a... assessment of t... high-intensity ... multiparametric... quality-of-life... transperineal p... transrectal pro...	- 90 Years	University College, London
Whether Transperineal Prostate Biopsy Under Local-anaesthesia Using a Transperineal-access System is Non-inferior to Standard Transrectal Biopsy to Detect Prostate Cancer in Biopsy-naïve Men	NCT04108871	Prostate Cancer Prostatic Hyper...	Prostate Biopsy	40 Years - 80 Years	The University of Hong Kong

Spots Global Cancer Trial Database for transrectal prostate biopsy