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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Prostate Cancer, Prostatic Hyperplasia

Intervention / Treatment
-----------------
* Procedure: Prostate Biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Serum PSA larger or equal to 20ng/mL Suspected tumour clinical stage T2 on DRE No previous history of prostate biopsy Medically fit to undergo procedures according to study protocol Exclusion Criteria: Patients who are unable to provide written informed consent Known history of prostate cancer Contraindication to prostate biopsy Had pre-biopsy mpMRI Rectal abnormality precluding transrectal ultrasound

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transperineal Prostate Biopsy<br>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. | Procedure: Prostate Biopsy<br>* 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.<br>|
| Active Comparator: Transrectal Prostate Biopsy<br>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). | Procedure: Prostate Biopsy<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of prostate cancer | 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. | When histopathology results available, expected to be within 14 days following biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure tolerability | The pain score of the procedure reported by patient | Immediately following test | 
| General health-related quality of life | EQ-5D-5L | Baseline and 30 days post-biopsy | 
| Quality of life concerning urinary symptoms | International Prostate Symptom Score (I-PSS) | Baseline and 30 days post-biopsy | 
| Quality of life concerning erectile function | International Index of Erectile Function (IIEF) | Baseline and 30 days post-biopsy | 
| Rate of procedure induced sepsis |  | 1 week to 30 days post-biopsy | 
| Detection rates of patients with clinically significant PCa | Ca Prostate with Gleason score larger or equal to 3+4 | When histopathology results available, expected to be within 14 days following biopsy | 
| Maximum cancer core length (MCCL, mm) |  | When histopathology results available, expected to be within 14 days following biopsy | 
| Proportion of men go on to undergo definitive curative treatment for local disease (including surgery and radiotherapy) |  | After treatment decision, expected to be within 30 days following biopsy | 
| Procedure times (minutes) | Time from start of ultrasound probe insertion to probe removal | During test | 
| Cost per diagnosis of cancer (HKD) | The cost of each diagnosis based on the equipment, manpower and medication | 30 days post-biopsy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Biopsy, Transperineal Prostate Biopsy, Prostate Cancer Detection, Transrectal Prostate Biopsy