A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

Study Overview
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Brief Summary
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The main purpose is to compare the detection rate of 20-core versus 12-core prostate biopsy. The secondary objective is to evaluate pain perception using a validated scale to compare the analgesia provided by the two different local anesthesia schemes. Data will be prospectively collected from patients who will undergo prostate biopsy in a single high volume urology center. The patients will be randomized to two different biopsy samplings and two local anesthesia schemes.

Detailed Description
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Prostate cancer is male's leading solid non-cutaneous tumor, and the second cause of cancer death in western countries. The main risk factors are age (5th decade or more), family history and life-style (low physical activity and occidental dietary habit). Due to it's high incidence and mortality, the screening protocols continue to be supported worldwide by the urologic and oncologic societies. The diagnosis of this disease needs histological evidence that is obtained by prostate biopsy which is indicated when prostate specific antigen (PSA) serum levels are elevated or there is suspicion at digital rectal examination. Actual estimations conclude that more than 200.000 new cases are diagnosed per-year in US and much more patients are submitted to biopsies; turning prostate biopsy a routine medical procedure. In therms of current medical evidence there is controversy in some biopsy aspects. The ideal number of fragments to be obtained is not well established. While twelve core is believed to be the minimum to be sampled, the maximum number is not clear. To ease the estimation of the number of necessary core at biopsy the literature recommend the use of nomograms; they adequate the number of removed fragments according to each individual characteristics such as age, volume, previous biopsy and PSA levels. The prostate biopsy is considered a painful procedure by 96% of patients, therefore it is fundamental to soften the soreness employing some form of anesthesia. There is no consensus regarding the ideal protocol but the local anesthesia with the periprostatic blockade is the most employed worldwide. However there is a controversy related to the site of the injection during the periprostatic block in terms of efficacy: base versus apex or both sites. Considering the epidemiological importance of prostate cancer detection in a continuous aging population, this study protocol was enrolled in a single center high volume urology Brazilian Public Hospital. The patients will be randomized at a 1:1 ratio for the two biopsy schemes and for the two anesthesia templates.The main objective was to compare the detection rate of two different prostate biopsy schemes 20-core versus 12-core prostate biopsy guided by transrectal ultrasound. Secondary objectives were to evaluate pain perception of the two local anesthesia schemes using a validated pain scale. The pain was evaluated using the visual pain scale immediately after the biopsy and one hour after the procedure. The patients were contacted by phone one week after the biopsy to assess the occurrence of any complication. The investigators then compared the major and minor complication rates of 20-core versus 12-core protocol using the Clavien-Dindo scale. In those patients with cancer at the pathologic report that underwent radical prostatectomy, the investigators will also compare the concordance of Gleason score between the biopsy versus surgical specimen according to the biopsy scheme 20-core versus 12-core. Data was collected since mid 2012 up to june 2016, inclusion and exclusion criteria will be detailed elsewhere. All information was obtained by the main investigator and all procedures were supervised by the main investigator as well.

Official Title
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A Randomized Controlled Trial To Assess and Compare the Outcomes of 20-core Versus 12-core Prostate Biopsy

Conditions
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Prostate Cancer, Local Anesthesia, Prostate-Specific Antigen/Blood, Biopsy/Methods, Image-guided Biopsy/Methods, Prostatic Neoplasms/Diagnosis, Prostate/Pathology, Prospective Studies, Humans, Male, Ultrasonography, Interventional/Methods

Intervention / Treatment
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* Other: 20 core-biopsy fragments
* Procedure: Base and apex local anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Formal indication to prostate biopsy: PSA elevation, positive digital rectal examination of prostate, prostate cancer active surveillance protocols. Patients signing the consent therm agreeing to participate in the trial Exclusive local anesthesia prostate biopsy. Exclusive transrectal ultrasound guided prostate biopsy. Exclusion Criteria: Transperineal ultrasound guided prostate biopsy Magnetic resonance cognitive fusion biopsy. Previous treatment with radiation therapy or brachytherapy. Previous treatment with focal therapy Previous androgen deprivation therapy

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 core-biopsy fragments<br>Patients submitted to experimental intervention (extended sextant biopsy with 20 cores) compared to current standard biopsy protocol (extended sextant biopsy with 12 cores) guided by transrectal ultrasound. | Other: 20 core-biopsy fragments<br>* Using the extended sextant fashion prostate biopsy, this randomized group was submitted to a 20-fragments core-biopsy to evaluate the diagnostic power, pain perception and complications comparative to institution's standard 12 cores.<br>Procedure: Base and apex local anesthesia<br>* Using the institution's standard local anesthesia protocol (base injection) as active comparator group, this randomized group was submitted to base and apex local anesthetic application to evaluate tolerability of the procedure, pain perception (with use of previous validated analogue pain scale) and complications.<br>|
| Experimental: Base and apex local anesthesia<br>Patients submitted to experimental intervention in prostate-biopsy anesthetic protocol (prostate base and prostate apex bilateral local anesthetic injection) compared to participants submitted to current standard anesthetic protocol in institution (prostate base bilateral local anesthesia) guided by transrectal ultrasound. guided by transrectal ultrasound. | Other: 20 core-biopsy fragments<br>* Using the extended sextant fashion prostate biopsy, this randomized group was submitted to a 20-fragments core-biopsy to evaluate the diagnostic power, pain perception and complications comparative to institution's standard 12 cores.<br>Procedure: Base and apex local anesthesia<br>* Using the institution's standard local anesthesia protocol (base injection) as active comparator group, this randomized group was submitted to base and apex local anesthetic application to evaluate tolerability of the procedure, pain perception (with use of previous validated analogue pain scale) and complications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with prostate cancer detected. | Statistical evaluation comparing detection of prostate cancer in 12-core versus 20 cores. | Through study completion, an average of four years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complications | Comparison of data between 12 versus 20 core-biopsy and base versus base plus apex anesthesia in therms of complication occurrence. | Immediate, early (30 minutes) and late (within first week) | 
| Core biopsy accuracy. | Comparison of cancer positive pathology data between 12 and 20 core-biopsy with their respective radical prostatectomy hole mount pathology specimen (when treatment was indicated). | Through study completion, at time of surgery. | 
| Pain perception using pain analogue scale. | Compare pain perception of two anesthesia scheme base versus base plus apex using the visual pain analogue scale immediately after the biopsy and 30 minutes later. The investigators will also compared the analgesia of these schemes according to PSA, PSA density, free/total PSA ratio, prostate volume, previous biopsy. | Immediate and early (30 minutes after biopsy). | 
| Number of participants with prostate cancer detected according to PSA value | The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA value. | Through study completion, an average of four years. | 
| Number of participants with prostate cancer detected according to PSA density. | The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA density. | Through study completion, an average of four years. | 
| Number of participants with prostate cancer detected according to free/total PSA ratio. | The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA free/total PSA ratio. | Through study completion, an average of four years. | 
| Number of participants with prostate cancer detected according to prostate volume. | The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to prostate volume. | Through study completion, an average of four years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatic Neoplasms, Biopsy, Anesthesia, Detection