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

Pharmaceutical Solutions

All Drugs and Chemicals

A new solution for guiding the surgeon in RALP is image-guided navigation using transrectal ultrasound (TRUS). A TRUS-guided intraoperative navigation system using a robotic ultrasound probe manipulator (TRUS Robot) has been developed. The research is a pilot clinical trial of the TRUS Robot and three-dimensional (3-D) navigation software to test its image-guidance ability of helping the surgeon during RALP. This is a dual robot approach, a Tandem-RALP (T-RALP). The TRUS Robot allows a steady holding as well as remote manipulation of the TRUS probe. In addition, the TRUS Robot can track the accurate position of TRUS probe which allows 3-D reconstruction of the images.

3-D TRUS navigation software during T-RALP

Misop Han, M.D., M.S.

A new solution for guiding the surgeon in robot-assisted laparoscopic radical prostatectomy (RALP) is image-guided navigation using transrectal ultrasound (TRUS). A TRUS-guided intraoperative navigation system using a robotic ultrasound probe manipulator (TRUS Robot) has been developed. The proposed research is a pilot clinical trial of the TRUS Robot and three-dimensional (3-D) navigation software to test its image-guidance ability of helping the surgeon during RALP. This is a dual robot approach, a Tandem-RALP (T-RALP). The TRUS Robot allows a steady holding as well as remote manipulation of the TRUS probe. In addition, the TRUS Robot can track the accurate position of TRUS probe which allows 3-D reconstruction of the images. While the intraoperative TRUS findings will not be used in surgical decision making in this trial, the use of TRUS imaging during radical prostatectomy can potentially improve the visualization of the NVB and subsequently improve postoperative recovery of potency in men. In addition, the 3-D reconstruction images of the prostate gland can potentially provide clear and accurate guidance of surgical landmarks to the surgeon..

The preservation of the neurovascular bundle (NVB) including cavernous nerves during radical prostatectomy improves the postoperative recovery of sexual potency. At present, the location of NVB is determined by the surgeon's visual estimation. However, NVB is difficult to visualize with simple visual magnification of the surgical field with surgical loupes or laparoscopic lenses due to the periprostatic connective tissue and intraoperative hemorrhage. One approach to better estimate the location of the NVB is to identify a macroscopic landmark to more clearly direct the surgeon to the location of the NVB. The accompanying arteries and veins in the NVB, which are visible with Doppler ultrasound, can serve as a macroscopic landmark to localize the microscopic cavernous nerves in the NVB. Therefore, the use of TRUS imaging during radical prostatectomy can potentially improve the visualization of the NVB and subsequently improve postoperative recovery of potency in men. In addition, the 3-D shape of the prostate gland can potentially be clearly and accurately delineated in ultrasounds imaging, providing direct guidance of landmarks to the surgeon.

Recently, intraoperative TRUS imaging has been used to visualize the prostate gland and NVB during laparoscopic radical prostatectomy (LRP). The investigators reported that the intraoperative use of TRUS was helpful in imaging the location and local extent of hypoechoic area(s), providing real-time guidance for the surgeon during NVB release and apical dissection of the prostate, and monitoring a calibrated, lobe-specific, wider dissection around a cancer nodule with suspected extracapsular extension (ECE). With the enhanced visualization of the surgical field by TRUS imaging, they reported significant improvement in NVB preservation and a decreasing rate of positive surgical margin, which is a surrogate for the technical quality of the surgery. However, several aspects related most likely to technology limitations can further be improved. For example, the TRUS probe was manipulated by a human assistant during LRP, compromising image stability especially with Doppler imaging, discarding the pose of the images, and performing navigation based on the recommendations of the assistant rather than using an actual navigation software. Moreover, their application of TRUS can be used in the non-robotic LRP only, because the daVinci® robot used in RALP occupies the place of a human assistant at the end of the operative table. Finally, there was no objective measure to quantify the performance of the navigational aid.

Regardless of the study's shortcomings, the authors reported that their positive surgical margin rates decreased precipitously since their use of the TRUS guidance, demonstrating potential benefit of the TRUS-based guidance during surgery. Since their study, the use of intraoperative TRUS guidance during prostate surgery has not gained wide acceptance, and was, in fact, criticized because it requires an additional personnel with an expertise in TRUS. Alternatively, we propose to use the TRUS Robot, a robotic arm to hold and manipulate the TRUS probe remotely, allowing the surgeon to manipulate the TRUS probe without the need for a human assistant during RALP. We also propose to use 3-D TRUS navigation with the images obtained by the TRUS.

Ultrasound-Guided Navigation in Robot-Assisted Laparoscopic Radical Prostatectomy

To assess whether NVB localization is accurate using the TRUS Robot and 3-D TRUS navigation software during T-RALP \& can accurately locate and quantify the distance between anatomical landmarks.

To determine T-RALP can be safely performed without increased complications including rectal injury.

Johns Hopkins University

Associate Professor

Carcinoma

Patients may undergo TRUS prior to standard-of-care radical prostatectomy. Following radical prostatectomy, removed glands are scanned and micro-US, standard of care mpMRI, and whole mount images are analyzed and compared.

Digital Image Analysis

Undergo standard of care radical prostatectomy

Radical Prostatectomy

Transrectal Ultrasound

Leonard S Marks

This trial studies the ability of micro-ultrasound to detect and characterize prostate cancer tumors in patients undergoing radical prostatectomy (removal of the entire prostate and some of the tissue around it). Usually multiparametric magnetic resonance imaging is used for the detection and targeted therapy of prostate cancer, but its accuracy remains imperfect. Micro-ultrasound may be superior as it provides real-time tumor visualization which may simplify and improve prostate cancer targeted therapy. This may also reduce the need for and substantial costs of radical prostatectomy.

PRIMARY OBJECTIVE:

I. Determine if micro-ultrasound (US) can be used to identify prostate cancer foci with equivalent (non-inferior) performance relative to multiparametric magnetic resonance imaging (mpMRI).

SECONDARY OBJECTIVE:

I. Determine if micro-US can be used to contour prostate cancer foci with equivalent (non-inferior) accuracy to mpMRI.

TERTIARY OBJECTIVE:

I. Determine if ex vivo micro-US images have quality comparable to in vivo micro-US images.

QUATERNARY OBJECTIVE:

I. Determine if micro-US can be used to evaluate suspicion of extracapsular extension (ECE) with equivalent (non-inferior) accuracy to mpMRI.

OUTLINE:

Patients may undergo transrectal micro-ultrasound scan (TRUS) prior to standard-of-care radical prostatectomy. Following radical prostatectomy, removed glands are scanned and micro-US, standard of care mpMRI, and whole mount images are analyzed and compared.

Micro-Ultrasound for the Detection and Localization of Prostate Cancer Tumors in Patients Undergoing Radical Prostatectomy

Micro-Ultrasound to Whole Mount Image Correlation for Detection and Localization of Prostate Cancer

Differences in in vivo versus ex vivo image quality will be evaluated by testing for systematic differences in tumor contouring accuracy. The measures will be identical to those listed under "secondary outcome measures" above, but for comparison between ex vivo micro ultrasound and in vivo micro ultrasound (instead of MRI).

Micro ultrasound and mpMRI ECE suspicion scores will be compared for ECE-positive tumors. Micro ultrasound and mpMRI ECE suspicion scores will also be compared for ECE-negative tumors.

Measurement tool(s) = Wilcoxon signed-rank test and one-sided non-inferiority t-test.

Notes on the use of Wilcoxon signed-rank tests: (see outcome 2 description above)

Will be evaluated by comparing sensitivity and positive predictive value of multiparametric magnetic resonance imaging (mpMRI) and micro-ultrasound (US) for identification of prostate cancer (CaP) foci.

Measurement tool = chi squared test

evaluated by measuring the dice similarity coefficient (DSC) and Hausdorff distances (Hd) between micro-ultrasound (US) and whole mount (WM) tumor contours, and between mpMRI and WM tumor contours. The difference between tumor diameter and volume will be computed between WM and mpMRI, and between WM and US. All measures will then be used to compare accuracy of US versus mpMRI.

Wilcoxon signed-rank tests:

Signed rank tests are nonparametric matched pair tests, here mostly used to compare correlation of mpMRI and WM v. correlation of US and WM. Minimum and maximum input values will depend on the metric being tested; min and max output values will vary between zero and one. A higher output indicates less difference in performance between mpMRI and US. A lower score indicates that more a difference between mpMRI and US. Whether a lower score is a better outcome or worse outcome depends on which modality (mpMRI vs US) is more strongly correlated with WM.

Exact Imaging

Phase One Foundation

Jonsson Comprehensive Cancer Center

Comparison of targeted transrectal ultrasound guided prostate biopsies based on 3T multiparametric MRI findings to systematic non-targeted transrectal ultrasound guided prostate biopsies

3T multiparametric MRI

Bk Medical Pro Focus Ultraview 2202 system

Transrectal ultrasound

Peter J Boström, Adj. Prof.

Prostate cancer has been the most common neoplastic disease in men in Finland over the last ten years. Prostate-specific antigen (PSA) plays an important role in screening of prostate cancer. However, PSA has a limited sensitivity and specificity for prostate cancer detection. Commonly, the diagnosis of prostate cancer is done by transrectal ultrasonography (TRUS) guided biopsy. Because of the low accuracy of TRUS a systematic biopsy is usually performed instead of targeted TRUS biopsy. While, as many as 47% of the ultra-sound guided biopsies may be false negative and biopsies carry a risk of increase in complications, there is an increasing interest in developing more accurate non-invasive imaging modalities.

This study will enroll 150 men with previous negative biopsies and clinical suspicion of prostate cancer due to serum level of PSA higher than 2.5 ng/ml or abnormal digital rectal examination (DRE) or patients in active surveillance due to low risk prostate carcinoma. Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) at 3 Tesla (T) magnetic field using surface coils will be used to non-invasively predict the presence or absence of prostate cancer. In addition to routine 12-core TRUS biopsies, targeted TRUS guided biopsy based on MRI findings will be performed.

Prostate Magnetic Resonance Imaging in Patient With Previous Negative Biopsies

Multiparametric MRI is performed in patients with previous negative biopsies with clinical suspicion of prostate cancer (elevated PSA and/or abnormal DRE) or in patients in active surveillance due to low risk prostate carcinoma. The accuracy will be determined using the results from transrectal ultrasound guided biopsies.

Turku University Hospital

Adj. prof.

Patients with suspected PCa who are scheduled to undergo an ultrasound fusion-MR prostate biopsy.

Sound waves are sent in a series and are expected to "push on" the prostate and move it a very small amount (the width of a hair). The stiffer the structure (prostate), the less it will move. This motion will be detected by the ultrasound system

Acoustic radiation force impulse (ARFI)

Standard ultrasound imaging session, ultrasound sound waves are sent into the tissue and bounce off of structures to make an image that appears on a screen

Ultrasound

Thomas Polascik, MD

Kathryn Nightingale, PhD

The purpose of this study is to evaluate a new ultrasound technique. This technique may provide additional and improved information about the stiffness and sizes of the internal structures of your prostate in order to improve the guidance for a targeted biopsy. The investigational, custom-designed probe and needle guide will be used to produce images of your prostate and provide guidance for up to 4 additional biopsy samples (cores) prior to a standard magnetic resonance (MR) ultrasound fusion biopsy procedure. Above the time required for the MR ultrasound fusion biopsy, this study will take up to 30 additional minutes of time for collection of the investigational device guided collection of biopsy samples Risks of participation include increased time under anesthesia (to collect additional biopsies) and slight heating of tissue.

ARFI Imaging for Targeted Prostate Biopsy

Acoustic Radiation Force Impulse (ARFI) Imaging for Targeted Prostate Biopsy

Length of carcinoma per cancer-positive biopsy specimen as reported by the pathology findings, computed from all cancer-positive biopsy specimens from a given biopsy approach for each participant in whom cancer of any grade was detected by any biopsy approach.

The grading system has five grade groups, 1 to 5. Grade group 1 (Gleason score ≤ 6) represents low or very low risk; grade groups 2 and 3 (Gleason score 3+4=7 and 4+3=7, respectively) represent intermediate risk; and grade groups 4 and 5 (Gleason score 8 and 9-10, respectively) represent high and very high risk. For each subject, the highest grade group detected by a given biopsy approach is assigned to that subject for that biopsy approach.

A commonly used method to classify how cells appear in cancerous tissues; the less the cancerous cells look like normal cells, the more malignant the cancer; two numbers, each from 1 to 5, are assigned to the two most predominant types of cells present. These two numbers are added together to produce the Gleason score with a total range of 2 to 10. Higher numbers indicate more aggressive cancers. For each subject, the highest Gleason score detected by a given biopsy approach is assigned to that subject for that biopsy approach.

The grading system has five grade groups, 1 to 5. Grade group 1 (Gleason score ≤ 6) represents low or very low risk; grade groups 2 and 3 (Gleason score 3+4=7 and 4+3=7, respectively) represent intermediate risk; and grade groups 4 and 5 (Gleason score 8 and 9-10, respectively) represent high and very high risk.

Duke University

Each participant was to undergo all three types of biopsy.

Patients with suspected PCa who are scheduled to undergo an ultrasound fusion-MR prostate biopsy.

Acoustic radiation force impulse (ARFI): Sound waves are sent in a series and are expected to "push on" the prostate and move it a very small amount (the width of a hair). The stiffer the structure (prostate), the less it will move. This motion will be detected by the ultrasound system. Regions suspicious for cancer in ARFI images are biopsied under ARFI imaging guidance.

Acoustic Radiation Force Impulse (ARFI)

Patients with suspected PCa who are scheduled to undergo an ultrasound fusion-MR prostate biopsy.

Ultrasound: Standard ultrasound imaging session, ultrasound sound waves are sent into the tissue and bounce off of structures to make an image that appears on a screen. MR fusion methods are used to provide imaging guidance to target biopsies.

MR-ultrasound Fusion

Patients with suspected PCa who are scheduled to undergo an ultrasound fusion-MR prostate biopsy.

Systematic sampling is a probability sampling method in which a random sample, with a fixed periodic interval, is selected from a larger population.

Systematic Sampling

Acoustic radiation force impulse (ARFI): Sound waves are sent in a series and are expected to "push on" the prostate and move it a very small amount (the width of a hair). The stiffer the structure (prostate), the less it will move. This motion will be detected by the ultrasound system. Regions suspicious for cancer in ARFI images are biopsied under ARFI imaging guidance.

Ultrasound: Standard ultrasound imaging session, ultrasound sound waves are sent into the tissue and bounce off of structures to make an image that appears on a screen. MR fusion methods are used to provide imaging guidance to target biopsies.

Systematic sampling: Biopsy specimens are obtained by sampling 12 pre-specified locations in the prostate, with standard ultrasound imaging guidance.

Patients With Suspected PCa Who Are Scheduled to Undergo an Ultrasound Fusion-MR Prostate Biopsy

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Kathy Nightingale, Ph.D.

Patients with suspected PCa who are scheduled to undergo an ultrasound fusion-MR prostate biopsy.

Systematic sampling: Biopsy specimens are obtained by sampling 12 pre-specified locations in the prostate, with standard ultrasound imaging guidance.

Participants who were imaged with that biopsy approach and in whom cancer of any grade was detected by any biopsy approach. All but one participant underwent all three types of biopsy. One subject did not undergo MR-ultrasound fusion biopsy, but did complete the other two procedures.

Number of Participants in Whom the Biopsy Approach Detected the Presence of Prostate Cancer (PCa) of Any Grade

Participants in whom cancer was detected by a given biopsy approach.

Length of Cancerous Tissue

Grade Group of Cancerous Tissue

Participants in whom cancer was detected by each biopsy approach.

Gleason Score

Participants in whom Grade Group 1 was the highest grade of cancer that was detected by any biopsy approach.

Number of Participants With Grade Group 1 Cancer, In Whom Cancer Was Detected

Participants in whom Grade Group 2 was the highest grade of cancer that was detected by any biopsy approach.

Number of Participants With Grade Group 2 Cancer, In Whom Cancer (of Any Grade) Was Detected

Number of Participants With Grade Group 2 Cancer, Graded as Grade Group 2

Participants who were imaged with that biopsy approach and in whom Grade Group 3 was the highest grade of cancer that was detected by any biopsy approach.

Number of Participants With Grade Group 3 Cancer, In Whom Cancer (of Any Grade) Was Detected

Number of Participants With Grade Group 3 Cancer, Graded as Grade Group 3

Participants in whom Grade Group 4 was the highest grade of cancer that was detected by any biopsy approach.

Number of Participants With Grade Group 4 Cancer, In Whom Cancer (of Any Grade) Was Detected

Number of Participants With Grade Group 4 Cancer, Graded as Grade Group 4

Participants in whom Grade Group 5 was the highest grade of cancer that was detected by any biopsy approach.

Number of Participants With Grade Group 5 Cancer, In Whom Cancer (of Any Grade) Was Detected

Number of Participants With Grade Group 5 Cancer, Graded as Grade Group 5

Overall Study

Infections

Symptoms and General Pathology

Wounds and Injuries

Communicable Diseases

Hyperthermia

Urinary Tract Infections

Fever

Sepsis

Toxemia

Anti-Infective Agents

Blood Substitutes

Micronutrients

Povidone-Iodine

Povidone

Anti-Infective Agents, Local

Iodine

Cadexomer iodine

Plasma Substitutes

The randomly selected group of subjects who will receive the intervention. The radiologist performing the transrectal prostate biopsy on these subjects will have a gauze soaked with Povidone-iodine over his/her index finger, and will insert this into the rectum. This gauze will be wiped back and forth across the prostate with the finger at least five times from one lateral margin to the other. This will be allowed to dry for 2 minutes before proceeding with the biopsy.

The randomly selected group of subjects who will receive the standard of care biopsy without any added intervention.

Povidone-iodine 10% solution. A piece of 10x10 cm gauze soaked in Povidone-iodine 10% solution wrapped around the index finger of the examiner is inserted into the rectum of the subject in arm A. This gauze will be wiped back and forth across the prostate with the finger at least five times from one lateral margin of the prostate gland to the other. The examiner will allow at least 2 minutes to elapse between antisepsis and the insertion of the first needle into the prostate in order to allow the Povidone-iodine to dry.

Povidone-iodine

Peter Black, MD, FRCSC

S. Larry Goldenberg, MD, FRCSC

Lindsay Machan, MD, FRCPC

Martin E. Gleave, MD, FRCSC

William Bowie, MD, FRCPC

Alan I. So, MD, FRCSC

Diane Roscoe, MD, FRCPC

Martin McLoughlin, MD, FRCSC

Kourosh Afshar, MD, FRCSC

Allen Rowley, MD, FRCPC

Alison Harris, MD, FRCPC

Anne Buckley, MD, FRCPC

Stephen Ho, MD, FRCPC

Audrey Spielmann, MD, FRCPC

Silvia Chang, MD, FRCPC

Zeid AbuGhosh, MD, FEBU

During a prostate biopsy, a needle is guided through the rectum into the prostate. Although patients are given antibiotics before the biopsy, there is still a risk of bacteria getting from the rectum into the bladder, prostate and bloodstream during the biopsy. For most surgical procedures, the surgical field is cleaned with antiseptic solution, but this is not common practice for prostate biopsies. In this study patients undergoing prostate biopsy will be randomly assigned to either receive an antiseptic preparation of the rectum or no preparation prior to biopsy, and the rate of infection after the biopsy will be determined.

1. Purpose This research aims to determine the efficacy and safety of cleaning the rectal mucosa with antiseptic solution (Povidone-iodine) prior to transrectal prostate biopsy.
2. Hypothesis We hypothesize that prophylactic cleaning of the rectal mucosa with antiseptic solution prior to transrectal prostate biopsy will decrease the rate of infectious complications after biopsy. We believe that this can be achieved without any significant complications related to the antiseptic solution.
3. Justification Prostate cancer is the most common cancer in men. Since the diagnosis of prostate cancer requires a transrectal prostate biopsy, this procedure is performed frequently. More than 6000 biopsies are performed in British Columbia each year, and more than 1000 are performed at Vancouver General and UBC Hospitals (combined numbers). In these hospitals, the biopsy is performed by the radiologists using transrectal guidance. Subjects receive antibiotic prophylaxis in the form of ciprofloxacin for three days starting one day before the biopsy. They also instill an enema into the rectum a few hours before the biopsy to empty the rectum. Local anesthetic is injected through the rectal mucosa into the periprostatic space prior to the biopsy. Depending on the size of the prostate, between 8 and 12 cores of tissue are remove from the prostate by repetitive passes of the 18 gauge biopsy needle through the anterior rectal wall. Cleaning the rectum with an antiseptic solution prior to biopsy is not routinely practiced and is not considered a current standard of care.

   Despite routine antibiotic prophylaxis, prostate biopsies are associated with a considerable rate of infectious complications. Sepsis after biopsy is described in the literature with an incidence 0.1 to 2.0 %.

   Rate of sepsis has been determined in a retrospective but contemporary study of approximately 4500 biopsies at VGH/UBC to occur with a rate of 0.55% (Lange et al., submitted to Journal of Urology). Less severe but more common adverse events include urinary tract infection and fever, which both occur in approximately 10% of men undergoing biopsy.

   Cleaning the rectum prior to biopsy offers a potential method to decrease the risk of these infectious complications, and we propose the use of Povidone-iodine for this purpose. Surgical site disinfection is standard in most surgical procedures, and Povidone-iodine is a safe antiseptic utilized routinely for the surgical preparation of the body surface as well as mucosal surfaces, including the vagina, mouth and bowel. Park et al. reported that the mean number of colony-forming units decreased 99.9% after Povidone-iodine cleansing of the rectum. Hay et al. reported similar results with Povidone-Iodine enema administration when combined with metronidazole. Povidone-iodine has been shown to significantly reduce bacterial concentrations in the mucosa of the colon and rectum. Brown et al. reported that a Povidone-iodine enema provided a safe and effective means for preventing bacteremia and bacteruria after transrectal prostate biopsy. Furthermore, severe allergic reaction to Povidone-iodine is rare.
4. Objectives

The objectives of this study are:

1. To determine whether cleaning the lining of the rectum with an antiseptic solution before prostate biopsy is effective in decreasing the rate of three outcome variables:

   * Urinary Tract Infection
   * Fever
   * Sepsis
2. To determine at what rate bacteria are found in the rectum prior to biopsy that are resistant to ciprofloxacin.
3. To determine at what rate bacteria are found in the urine after biopsy, with or without rectal cleaning.
4. To determine any adverse reactions to antiseptic solution in the rectum.
5. Research Method All subjects undergoing transrectal prostate biopsy as clinically indicated and determined by the treating Urologist at Vancouver General Hospital and University of British Columbia Hospital will be considered for entry into this trial. If the subject consents to participation, he will be randomized to undergo prostate biopsy with rectal cleaning with antiseptic solution ("treatment" group) or without rectal cleaning ("control" group). A urine sample will be collected before and after biopsy and sent for routine culturing. A rectal swab will be taken before the biopsy (and before rectal cleaning in treatment group) and will be cultured in ciprofloxacin-enriched medium.

   In the treatment group, the radiologist performing the biopsy will wipe the rectal lining overlying the prostate with gauze soaked with Povidone-iodine. Otherwise the biopsy is performed in standard fashion in both groups. After the procedure, the subjects are instructed to measure and record their temperature every 6 hours for 48 hours. A telephone interview is conducted seven days after biopsy to ascertain any adverse events from the biopsy, including whether a temperature ≥38.0˚C was measured.
6. Statistical Analysis The primary outcome in this study will be the rate of urinary tract infection and the rate of fever after biopsy (see definitions below). The rate of sepsis will be measured, but the study will not be powered to detect a difference in the rate of sepsis.

   The rate of UTI and fever is estimated from the literature data at 10% each. A relative reduction of 50% (absolute reduction from 10% to 5%)would be considered clinically significant. With type I \& II errors set at 0.05 and 0.2, respectively, and a two-sided test of significance, the necessary sample size is estimated at 435 in each group. Assuming 20% inability to enroll and loss to follow up, the total sample size is 1044.

   Descriptive statistics of baseline parameters will be provided in each group. The mean, median, standard deviation or range of the variables will be computed as applicable. The association between exposure and the defined outcomes will be assessed in univariate analysis. The proportion of each outcome in each group will be compared using the chi square test. Multivariate analysis using logistic regression will be performed to assess effect of variables such as age, number of biopsy cores, individual performing the biopsy and other co-morbidities. A test of interaction will be performed.
7. Definition of Endpoints

   * Urinary tract infection: \> 100 million colony forming units per liter in the urine culture obtained48 hours after biopsy.
   * Fever: oral temperature ≥38.0˚C within 48 hours after biopsy.
   * Sepsis(19),(20): positive urine or blood culture plus two or more of the following within 1week of biopsy:

     1. temperature ≥38.0˚C or \< 36.0˚C,
     2. heart rate \>90 beats/minute,
     3. respiratory rate \> 20 breaths/min,
     4. WBC count \>12.0 or \<4.0 x 10 9/L, or \> 0.10 immature forms (bands).
8. Summary of Procedures:

Eligible subjects will be counseled in the office regarding the prostate biopsy as per each physician's routine. This includes instructions for ciprofloxacin prophylaxis (1000 mg of extended release ciprofloxacin daily for three days starting the day before the biopsy) and the use of a fleet enema at home approximately 2 hours before biopsy. The Urologist will also discuss this study with the subject at the same time as he/she orders the biopsy. He/she will ensure that the subject meets the eligibility criteria using a pre-biopsy questionnaire. The subject will be able to take the consent home for further consideration and discussion. It must be signed before the biopsy for the subject to participate in the study.

Each subject will be assigned a study code. At the time of biopsy, subjects will be randomized 1:1 by computer generated random numbers into two groups. The first group ("controls") will undergo biopsy according to the current standard of care, which does not include antiseptic cleaning. The second group ("treatment") will undergo biopsy in the same fashion, but after cleaning the rectal lining with 10% Povidone-iodine.

Before the biopsy is started, the subject is asked to give a midstream urine sample for routine culture. A culture swab is also inserted into the rectum and then cultured in ciprofloxacin-enriched media in order to isolate ciprofloxacin-resistant rectal flora prior to the biopsy.

The control group will undergo the routine biopsy while in the treatment group, the radiologist performing the biopsy will have a gauze soaked with Povidone-iodine over his/her index finger, and will insert this into the rectum. Before this, the Radiologist asks the subject again if he has allergy to Povidone-iodine, shellfish or IVP dye. The gauze will be wiped back and forth across the prostate with the finger at least five times from one lateral margin to the other. The radiologist will allow at least 2 minutes to pass between prep and the insertion of the first needle into the prostate in order to allow the Povidone-iodine to dry. The radiologist will ask the subject to inform the Radiologist if the subject does experience any symptoms of allergic reaction (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue ). The 2 minutes will be spent measuring the prostate size using the rectal ultrasound probe. After those two minutes the routine biopsy is done. A second rectal swab for culture will not be taken, as this will likely be negative due to the Povidone-iodine contamination of the swab, and due to the added cost.

All subjects will be discharged from the recovery according to standard care. During the recovery period, a watchful eye is kept on the subjects in the treatment group for developing severe allergic reaction. A crash-cart will be available all the time during the procedure and in the recovery room. Should the subject develop an allergic reaction, the radiologist will take the necessary measures as per the Radiology Department standard of care protocol. The subjects will be asked to provide another midstream urine sample for routine culturing 2 days after the biopsy. This will be grown in conventional media. Subjects will be asked to measure and record their oral temperature once they wake up and just before going to sleep and every 6 hours in between, for 2 days after the procedure. A telephone interview using a post-biopsy questionnaire will be performed with the subject seven days after the biopsy to ascertain any side effects from the biopsy, including whether a temperature ≥38.0˚C was measured.

Prostate Biopsy Antisepsis

Antiseptic Preparation of the Rectum Prior to Transrectal Prostate Biopsy

University of British Columbia

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

Use of US for post implant quality assessment

transrectal ultrasound

Francois Bachand, MD

Post implant dosimetry is an essential part of quality assurance after permanent seed prostate brachytherapy. CT imaging is the standard of assessment but due to contouring uncertainties, MR-CT fusion is preferred. This is not always available due to financial restrictions. This study explores the possibility of post implant US-CT fusion to improve contouring accuracy and potentially replace the use of MR-CT fusion.

25 participants undergoing permanent seed prostate brachytherapy will be approached to undergo collection of prostate US images at the completion of their procedure. This will add approximately 5 minutes to the duration of their brachytherapy procedure. The US study will not entail any discomfort or risk to participants as they are still under anesthesia for the implant procedure. The institution standard of care for quality assurance will be complied with, obtaining a CT and MRI of the prostate at 30 days after the procedure. These will be co-registered and analyzed in the normal fashion. In addition, the post implant US images will also be co-registered with the CT and the resulting dosimetric parameters compared.

US-CT Fusion for Post Implant Dosimetry

Comparison Between Postoperative Ultrasound-CT Fusion With MRI-CT Fusion for Postimplant Dosimetry for Prostate LDR Permanent Seed Brachytherapy

Dosimetry will be calculated using 2 different imaging modalities (US vs MRI) and compared

Assessment of prostate volume as contoured on US vs MRI post implant

British Columbia Cancer Agency

Radiation Oncologist

TRUS and TRUS-Robot will be used during prostate biopsy

Just Uronav will be used during prostate biopsy

A robotic device used to hold and manipulate the ultrasound probe during a transrectal prostate biopsy.

TRUS-Robot

TRUS biopsy

Dan Stoianovici, PhD

Misop Han, M.D.

Prostate cancer (PCa) is the most common non-dermatologic malignancy in U.S. men. Transrectal ultrasound (TRUS)-guided prostate biopsy is a commonly used diagnostic procedure for men with an elevated serum prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE). It is estimated that more than 1 million TRUS-guided prostate biopsies are performed annually in the U.S. alone. However, a freehand TRUS-guided systematic biopsy (SB) procedure has significant limitations. First, freehand biopsy cores are often spatially clustered, rather than uniformly distributed, and do not accurately follow the recommended, sextant template. Second, a freehand TRUS-guided biopsy does not allow precise mapping of the biopsy cores within the prostate. Targeted biopsy (TB) using special devices emerged to help the physicians guide the biopsy using multiparametric MRI (mpMRI). TB cores yield a higher cancer detection rate of clinically significance PCa than SB cores, but TB cores also miss a large number of clinically significant PCa that are detected by SB. Accordingly, TB is commonly performed concurrently with SB (TB+SB procedure).

This study attempts to improve TRUS-guided prostate biopsy by utilizing assistance from a novel robotic TRUS manipulator (TRUS-Robot) developed by our team. The hypothesis of the study is that clinically significant prostate cancer detection rate from the SB cores (at SB or TB+SB) can be improved above that of current devices. The objective of the study is to gain early evidence on the effectiveness of prostate biopsy assisted by the TRUS-Robot vs. a current TB device in a randomized clinical trial.

Transrectal Ultrasound Robot-Assisted Prostate Biopsy

Number of biopsy patients diagnosed with Gleason score \>= 7 over the total number of patients on both arms of the study.

Serious adverse events will be assessed according to 21 Code of Federal Regulations (CFR) Part 812.3(s).

Number of biopsy patients diagnosed with Gleason score \<= 6 over the total number of patients on both arms of the study.

Needle targeting errors will be measured as the distance between the planned core center and the inserted needle axis. Targeting accuracy will be calculated as the average of the needle targeting errors, as usual.

The time of the actual biopsy procedure measured in minutes.

Compare biopsy pathology results with gold standard pathology on the subset of patients who follow on to radical prostatectomy. Perform binary tests (True/False x Positive/Negative) and calculate sensitivity.

Compare biopsy pathology results with gold standard pathology on the subset of patients who follow on to radical prostatectomy. Perform binary tests (True/False x Positive/Negative) and calculate specificity.

Compare biopsy pathology results with gold standard pathology on the subset of patients who follow on to radical prostatectomy. Perform binary tests (True/False x Positive/Negative) and calculate predictive rates.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ultrasound-Guided Navigation in Robot-Assisted Laparoscopic Radical Prostatectomy	NCT00956904	Prostate Cancer	3-D TRUS naviga...	35 Years - 75 Years	Johns Hopkins University
Micro-Ultrasound for the Detection and Localization of Prostate Cancer Tumors in Patients Undergoing Radical Prostatectomy	NCT04299620	Prostate Carcin...	Digital Image A... Radical Prostat... Transrectal Ult...	18 Years -	Jonsson Comprehensive Cancer Center
Prostate Magnetic Resonance Imaging in Patient With Previous Negative Biopsies	NCT02388126	Prostate Cancer	3T multiparamet... Transrectal ult...	40 Years - 80 Years	Turku University Hospital
Ultrasound-Guided Navigation in Robot-Assisted Laparoscopic Radical Prostatectomy	NCT00956904	Prostate Cancer	3-D TRUS naviga...	35 Years - 75 Years	Johns Hopkins University
Prostate Magnetic Resonance Imaging in Patient With Previous Negative Biopsies	NCT02388126	Prostate Cancer	3T multiparamet... Transrectal ult...	40 Years - 80 Years	Turku University Hospital
ARFI Imaging for Targeted Prostate Biopsy	NCT04607135	Prostate Cancer	Acoustic radiat... Ultrasound	18 Years -	Duke University
Prostate Biopsy Antisepsis	NCT00999427	Infective Compl...	Povidone-iodine	21 Years -	University of British Columbia
Ultrasound-Guided Navigation in Robot-Assisted Laparoscopic Radical Prostatectomy	NCT00956904	Prostate Cancer	3-D TRUS naviga...	35 Years - 75 Years	Johns Hopkins University
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
US-CT Fusion for Post Implant Dosimetry	NCT03692104	Prostate Cancer	transrectal ult...	40 Years - 80 Years	British Columbia Cancer Agency
US-CT Fusion for Post Implant Dosimetry	NCT03692104	Prostate Cancer	transrectal ult...	40 Years - 80 Years	British Columbia Cancer Agency
Transrectal Ultrasound Robot-Assisted Prostate Biopsy	NCT02871726	Prostate Cancer	TRUS-Robot TRUS biopsy	45 Years - 75 Years	Johns Hopkins University

Spots Global Cancer Trial Database for transrectal ultrasound