PK Button Vaporization Electrode for Treatment of Bladder Tumors
Phase: NA
Conditions: Bladder Cancer
Sponsor: Emory University

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PlasmaKinetic (PK) Button Vaporization Electrode for Treatment of Bladder Tumors 
 
NCT01567462 
 
02/13/2015

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PK Button Vaporization Electrode for Treatment of Bladder Tumors 
Clinical Protocol Outline 
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Title:  PK Button Vaporization Electrode for Treatment of Bladder Tumors 
Principal Investigator: Kenneth Ogan, MD  
Sub Investigator: Adeboye Osunkoya, MD 
Co-Investigators: Daniel Canter, MD, Viraj Master, MD PhD, Peter Nieh, MD, Kenneth Ogan, MD, 
John Pattars, MD 
Study-Supporter: Olympus78 
Draft Date: 2012-01-31 
 
1. Hypothesis:  
 
It is hypothesized that the PK Button Vaporization Electrode is a non-inferior device in terms of 
composite complication rates when compared with traditional monopolar electrocautery in the 
treatment of patients with bladder cancer. 
 
2. Abstract: 
The current treatment standard of care for patients who present de novo or with a recurrent bladder 
tumor is transurethral resection of the bladder tumor (TURBT) using monopolar electrocautery in the 
form a 90-degree loop electrode and has been used since its introduction in 1952. This intervention, 
accomplished endoscopically through the urethra, is both diagnostic and potentially therapeutic. 
Although usually safe and sufficient, this technique can create technical challenges which in this 
study are to be compared to the use of bipolar energy in TURBT. Bipolar energy has been available 
for many years and has been readily adopted for the surgical treatment of benign prostatic 
enlargement and may provide advantages and solutions to the technical challenges of monopolar 
electrocautery. A further refinement on bipolar energy has been the recent introduction of the PK 
Button Vaporization electrode which will be used in the intervention arm of this study. A minimum 
of 120 patients over approximately 2.5-3.0 years will be enrolled and randomized onto one of the two 
study arms (control-monopolar electrocautery vs. intervention-PK Button Vaporization). The purpose 
of this study is to measure the procedural (intraoperative), short term, as clinically indicated, (4-6 
weeks), and long-term (3 months) outcomes of TURBT using the PK Button when compared to 
traditional monopolar loop electrocautery.  The goal of the study will be to prove equivalence in 
outcomes between the two techniques based on the comparison of complication rates. The control 
arm of the traditional monopolar loop electrode is expected to have a composite complication rate of 
10-15%. It is hypothesized that the PK Button Vaprization Electrode is a non-inferior device in terms 
of overall complication rates when compared with traditional monopolar electrocautery in TURBT 
procedures. 
 
3. Background:  

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The burden of bladder cancer in the United States is enormous.  In 2011 alone, there will be nearly 
70,000 new cases with approximately 15,000 deaths.i  These statistics do not account for the huge 
number of patients with superficial or non muscle-invasive bladder cancer (NMIBC) who require 
continual cystoscopic surveillance and tumor resection when recurrences occur. 
 
The current treatment standard of care for patients who present de novo or with a recurrent bladder 
tumor is transurethral resection of the bladder tumor (TURBT).  This intervention, accomplished 
endoscopically through the urethra, is both diagnostic and potentially therapeutic. An adequately 
performed TURBT will provide the pathologist with enough tissue to provide tumor grade and stage 
information.  Adequate cancer staging is the most important component in determining the correct 
treatment paradigm for any patient with a bladder tumor.ii  If the tumor invades the muscularis 
propria--the muscular wall of the bladder--a radical cystectomy with urinary diversion is the current 
gold standard therapy.  For patients in whom the tumor does not extend into the muscularis propria, 
complete TURBT with or without intravesical chemo/immunotherapy is recommended.ii above   
 
Currently, TURBT using monopolar electrocautery in the form a 90-degree loop electrode has been 
used since its introduction in 1952. Although usually safe and sufficient, this technique can create 
technical challenges because it can be difficult to position the loop electrode in a dynamically 
changing cylindrical space (the bladder). Specifically, especially with larger bladder tumors, 
intraoperative bleeding can obscure visualization and result in incomplete tumor resection as well as 
inadequate sampling of the layers of the bladder needed to establish tumor stage.  Furthermore, 
monopolar current can result in stimulation of the obturator nerve during resection of lateral wall 
tumors, resulting in violent adduction of the leg with potential bladder perforation as well as possible 
iliac vessel injury.iii below 
 
Conversely, bipolar energy, which has been available for many years, has been readily adopted for 
the surgical treatment of benign prostatic enlargement.iii  The advantages of a bipolar electrical 
current include the direct return of current to the loop rather than to the grounding pad placed on the 
patient’s skin. This has the theoretical value of limiting the diffusion of current, and therefore heat, to 
the surrounding tissue.  A further refinement on bipolar energy has been the recent introduction of the 
PK Button Vaporization electrode.iii above The semi-spherical design of the electrode creates a 
plasma arc that glides over the tissue, transmitting energy to the cell layers adjacent to the arc which 
are then quickly vaporized. Coupling bipolar energy into the Button electrode would not only harness 
the benefits of less thermal spread but also would obviate the geometric challenges associated with 
loop electrodes during resection of bladder tumors. Procedural advantages would potentially include 
minimal bleeding, good visualization, and a reduction in the occurrence of the obturator reflex and 
concomitant bladder perforation.iii above 
 
4. Objective:  
Currently, monopolar electrocautery is the goal standard in treating patients with bladder tumors 
mainly due to its extensive use since being introduced in 1952. While other devices, such as the PK 
Button, are now available, there have not been any US studies done in order to assess non-inferiority. 
The purpose of this study is to measure the procedural (intraoperative), short term, as clinically 
indicated, (4-6 weeks), and long-term (3 months) outcomes of TURBT using the PK Button when 
compared to traditional monopolar loop electrocautery. The goal of the study will be to prove 
equivalence in outcomes between the two techniques by comparing the rate of complications between 
the two arms. 

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3.1 Primary Objective 
The primary endpoint will be the measurements of procedural complications, which include 
post-operative bleeding, need for blood transfusion, bladder perforation, obturator nerve 
stimulation, or need for hospitalization or bladder irrigation. The expected rate of composite 
complications is 10-15%. If one or more of the aforementioned complications occur, then the 
case will be recorded to have a complication. 
 
3.2 Secondary Objective 
The secondary endpoints will be the assessment of operative time, tumor recurrence, 
catheterization time, and amount of thermal spread or cautery artifact in biopsies of tumor 
base. 
 
It is hypothesized that the PK Button Vaprization Electrode is a non-inferior device in terms of 
complication rates when compared with traditional monopolar electrocautery in TURBT procedures. 
 
5. Study Design:  
  The number of subjects will be a minimum of 120 patients.  This is the first US study 
comparing the use of the PK Button electrode for the ablation/treatment of bladder tumors to 
the traditional monopolar loop electrocautery. The goal will be to collect data to confirm the 
efficacy and safety of the PK Button electrode vaporization procedure.  The primary endpoint 
of the study is to verify equivalence or non-inferiority to monopolar loop electrocautery 
technique as measured by comparing the rate of complications from postoperative bleeding, 
need for blood transfusion, bladder perforation, obturator nerve stimulation, and need for 
hospitalization.  Secondary endpoints will include operative time, tumor recurrences (overall, 
at original TUR site, and elsewhere), catheterization time, and amount of thermal spread 
detectable in biopsies of tumor base.  It is expected that the monopolar loop electrocautery 
arm will have a composite complication rate of 10-15% based on clinical experience, though 
this number is often inconsistently reported based on the subjective analysis of the degree of 
complication. It is hypothesized that the PK Button Electrode arm will have the same or lower 
rate of composite complications during the procedure. 
 
 
  Pre-operative, intraoperative, short term as clinically indicated (4-6 weeks), and long-term (4 
months) criteria will be measured.   
 
  The study will be performed at Emory University Hospital, Saint Joseph’s Hospital,  and 
Grady Hospital, Atlanta, Georgia. 
 
  The estimated time frame needed to include the number of subjects is 24-30 months. 
 
  The type of investigation will be a two arm randomized study with patient treatment 
consisting of TURBT using the PK Button Electrode and the control group undergoing 
TURBT using the monopolar loop electrode.  The goal will be to collect procedural, short 

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term, and long term follow up data to compare the bipolar vaporization and monopolar 
electrocautery data.The primary and secondary endpoints of the study  
o Primary endpoint:  the composite complication rate assessing the occurrence of one or 
more of the following:  
o 
Post-operative bleeding 
o 
Need for blood transfusion 
o 
Bladder perforation based on surgeon’s examination of bladder 
o 
Obturator nerve stimulation 
o 
Need for hospitalization; need for continuous bladder irrigation 
 
o Secondary endpoints: 
o 
Operative time 
o 
Tumor recurrence 
o 
Catheterization time 
o 
Amount of thermal spread/cautery artifact in biopsies of tumor base 
 
Measures will be taken to minimize and avoid bias.  The patients will be randomized and care 
will be taken to match cohorts for age, co-morbidity, tumor size, tumor number, tumor location, 
and tumor stage.  Randomization will occur after the informed consent has been obtained from 
the patient and the process has been documented. Patients will be randomized 1:1 (monopolar 
loop vs. pk button). Study coordinator will place six pre-labeled pieces or paper (three monopolar 
loop and three pk-button) in an envelope. Each time patient consents to participate in the study, 
study coordinator will randomly pick a paper from the envelope which will have the 
randomization arm written on it. Study coordinator will not place the paper back into the envelope 
in order to ensure true 1:1 randomization for six patients at the time. Once all six papers have 
been picked from the envelope, the process will be repeated.  
  Measurements will include: 
 
Patient Measurements:   
o Pre-operative: 
 
Cystoscopic confirmation of papillary bladder tumor requiring TURBT 
 
Urine cytology 
 
Upper tract study/cross-sectional imaging to exclude nodal/metstatic  
 
disease 
 
CBC, comprehensive metabolic panel, coagulation studies 
 
o Intra-operative/peri-operative: 
 
Operative time 
 
Post-operative bleeding 
 
Need for blood transfusion 
 
Bladder perforation 
 
Obturator nerve stimulation 
 
Catheterization time 
 
Need for hospitalization; need for continuous bladder irrigation 
 

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o Short-term (4 weeks or closest standard of care (SOC) visit) as clinically indicated for 
subjects with high-grade T1 disease who require re-resection after initial pathologic 
review: 
 
Repeat cystoscopic exam to determine residual/recurrent disease at  
 
original TUR site and elsewhere in bladder 
 
Biopsy of tumor base to re-assess thermal spread/cautery artifact 
 
o Long-term (4 months or closest standard of care (SOC) visit): 
 
Repeat cystoscopic exam to determine presence of recurrent disease 
 
 
Safety Measurements: 
o Complication Rate:  Intraoperative complications include obturator nerve reflex, 
bladder perforation, and bleeding.  Immediate post-op complications include bleeding 
and electrolyte change. 
o Operative Time (minutes): measured from scope insertion to scope removal. 
o Transfusion Rate 
o Catheterization Time (days) 
o Need for hospitalization based on intraoperative bleeding, electrolyte monitoring, or 
bladder perforation. 
o Serum hemoglobin/electrolyte levels will only be monitored as clinically indicated. 
 
Subjective Physician Intraoperative Criteria (Rated 1-5, 1 being “Excellent”, 5 being 
“Unacceptable”) 
o Intraoperative level of bleeding 
o Quality of Visualization 
o Ease of Use 
o Actual duration measured above. 
o All of above measurements will be taken on an intraoperative basis. 
 
  Comparisons to be made to the control. The control data will be collected in patients treated 
with the traditional monopolar loop electrocautery. True positives and false positives will be 
assessed in the statistical consideration. 
 
  Duration of the investigation will be approximately 2.5-3.0 years. If there are unforeseen 
complications resulting in patient cases, investigators will discontinue enrollment. This case 
will be discussed at weekly Urology research meetings as well as monthly GU 
multidisciplinary meetings.

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6. Summary of Measurements 
 
Measurement Description 
Pre-Op 
Intra-Op 
Immediate 
Post-Op 
4 weeks 
Post-Op 
(or closest 
SOC 
visit) 
4 months 
Post-Op 
(or closest 
SOC 
visit) 
Cystoscopy confirming bladder tumor 
X 
 
 
X 
X 
Biopsy of tumor base and resection of new tumors 
 
 
 
X 
 
Urinary cytology 
X 
 
 
 
 
CBC, comprehensive metabolic panel 
X 
 
 
 
 
INR Anticoag Measurement 
X 
 
 
 
 
Upper tract/cross-sectional imaging to exclude 
nodal/metastatic disease 
X 
 
 
 
 
Complication Rate 
 
X 
 
 
 
Operative Measurements 
Operative Time, Blood Loss, Transfusion Rate, 
Bladder perforation, obturator nerve stimulation, 
need for continuous bladder irrigation 
 
X 
X 
 
 
Catheterization Time 
 
X 
X 
 
 
Need for hospitalization 
 
 
 
 
 
Operative Subjective Measurements 
Visualization, Ease of Use, Duration 
 
X 
 
 
 
 

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7. Study Equipment 
a. Cysto-Resection PK Button Equipment 
Each physician will use the following set of cysto-resection equipment for the PK Button 
portion of the study. 
 
Description (can be changed) 
Item Number 
SuperPulse Generator with Footswitch 
 
Elite 1 Continuous Flow Rotating Inner Sheath 
ERIS-CF25 
Elite 1 Continuous Flow Rotating Outer Sheath 
EROS-CF25 
Visual Obturator for Inner Sheath 
ERTO-CF25 
Standard Obturator for Inner Sheath 
ERSO-CF25 
Iglesias PK Front Loading Working Element 
EIWE-PKFL 
M3 Gold 30 Degree Telescope 
M3-30A 
PK Button Electrode with Cable 
786500 
 
b. Traditional monopolar loop electrocautery available in OR at Emory University 
Hospital or Grady Hospital. 
 
 

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8. Study Participation: 
The number of subjects will be a minimum of 120 patients. Duration of the investigation will 
be approximately 2.5-3.0 years. 
 
  Inclusion criteria 
o Patients with cystoscopically detected bladder tumors requiring TURBT 
o Patients with bladder tumors which are endoscopically resectable by surgeon’s 
judgment with only one trip into the operating room. 
o Age ≥18 years 
  Exclusion criteria 
o Patients with clinical evidence of locally advanced, nodal, or metastatic bladder 
cancer 
o Patients with hydronephrosis secondary to bladder cancer 
o Patients with diffuse tumor throughout bladder that is deemed unresectable by 
surgeon 
  Recruiting tools will not be formally utilized. 
  Screening procedures 
o Local cystoscopy 
o Upper tract/cross-sectional imaging to exclude locally advanced/nodal/metastatic 
bladder cancer 
  Subject withdrawal and replacement criteria 
o Subjects that withdraw prior to undergoing treatment will be excluded from 
analysis and will be replaced by an additional subject. 
o Subjects that are lost to follow-up after treatment will also be excluded from 
analysis and will be replaced by an additional subject. 
 
9. Study Methods: 
  Description of device preparation 
 
o The investigational device and the monopolar loop electrocautery equipment will be 
prepared in a standardized fashion and all equipment will be autoclaved prior to 
each use: 
 

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 Working elements, telescopes, and sheaths, cables, and accessories will be 
removed from original packaging (if applicable) and inspected for integrity. 
 Working elements, telescopes, and sheaths, cables and accessories will loaded 
into sterilization trays.  All devices will then be sterilized in an autoclave steam 
sterilizer per parameters in the instructions for use. 
 After sterilization the devices will be stored or transported to the operating 
room. 
 Once in the OR, the devices will be transferred to the sterile table using 
accepted OR procedure for the handling of surgical devices.  The Resectoscope 
will be assembled by the physician or the operating room staff.. 
 The disposable devices will be transferred to the sterile field using accepted 
practice and assembled into the Resectoscope. 
 After the procedure the disposable product will be inspected and discarded.  The 
surgical devices undergo cleaning and sterilization according to the guidelines 
in the Olympus/ACMI resection equipment Instructions for Use. 
 
  The procedural use of the device(s)  
 
o The TURBT Button Vaporization technique will be standardized for each patient.  
Prior to beginning vaporization, a bladder wash and a cold-cup biopsy of the 
primary tumor will be taken in order to obtain tumor grade information.  Since 
tumor vaporization results in no pathologic tissue for review, this step is necessary 
in order to obtain adequate grade information for each individual patient.  Tumor 
vaporization will then proceed systematically down to the tumor base.  At this 
point, multiple biopsies of the tumor base will be obtained either with the cold-cup 
biopsy forceps or a bi-polar loop as determined by clinical judgment to ensure 
adequate stage information. 
o Traditional monopolar loop electrocautery TURBT will be performed in the usual 
fashion. 
o Regardless of procedure used, all patients will receive intravesical mitomycin-C 
chemotherapy in the PACU post-operatively unless there is surgical concern for 
bladder perforation which is a contraindication for its use. 
 
  The procedure that the patient undergoes including any medication 
 
o All patients will receive peri-operative antibiotics 
o Hospital admission for overnight observation following surgery will be determined 
post-operatively and will be on an as needed basis.  The intent is for all study 
patients to be discharged home the same day as the procedure unless there is 
concern for bleeding or it is felt the patient requires overnight observation (e.g. 
perforation, etc.) 
o Foley catheter will be discontinued after post-operative intravesical therapy unless 
prolonged drainage is clinically indicated. 
o Patients will be prescribed pain medications, bladder spasm medications, and stool 
softeners as needed post-operatively 
 
 

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10. 
Statistical Consideration 
  Power estimation: this study is designed to establish the non-inferiority of PK Button 
Vaporization Electrode (arm 1) compared to the traditional monopolar loop electrode 
(arm2) in terms of complication rate. Based on the historical data, we assume that the 
complication rate in arm2 is 15% and the highest acceptable complication rate for claiming 
non-inferiority in arm 1 is 20%. By a sample size of 60 patients per group, we have 84% of 
power to detect a difference of -9% when the actual complication rate in arm1 is 6% by the 
one-sided Z test (pooled) at significance level of 0.05.  
 
  Statistical analysis plan:  
 
o The primary analysis will be conducted by pooled z test for comparison of 
complication rate in two arms.  
o For the secondary endpoints, the comparison between the two arms will be done 
using two-sample t-test/Wilcox sum rank test for continuous measurements, e.g. 
operative time, and Chi- square test/Fisher’s exact test for categorical ones, e.g. 
post-operative bleeding (Yes/No). Log-rank test will be performed for any time-to-
event outcome, e.g. time to recurrence. Multivariable regression model may be used 
to take potential confounders into account. For repeated measured outcomes, e.g. 
AUA/IPSS score over time, GEE model will be considered. 
 
11. Protocol Deviations 
Any deviations to the protocol will be noted and require approval of the study coordinators and 
appropriate Olympus personnel. 
 
12. Reference to Data Collection, Management and Analysis 
Data will be collected on individual data sheets for each patient.  The collected data will be entered 
into an excel spreadsheet for analysis and comparison to existing published data.  Statistical 
analysis will be performed on the data to determine means, standard deviation, and range. 
 
13. Acceptance criteria 
 Comparable intra-operative/peri-operative outcomes as detailed above 
 Comparable or improved IPSS scores post-operatively 
 Comparable or improved recurrence rates at 4 weeks or 4 months from 
original TURBT 
 Comparable or improved thermal spread/cautery artifact as reported by 
histologic review 
 
14. Risk Analysis  
Prior studies have shown that bipolar TURBT appears to be as safe as traditional monopolar 
TURBT with potentially less thermal spread/cautery artifact, which complicates pathologic review.  
Furthermore, one recent European study recently reported improved intra-operative/peri-operative 

13 
 
results with Button TURBT as compared to monopolar TURBT.  Also, in that study, there was the 
suggestion that recurrence rates were improved when using the Button. 
 
15. Publication Plan 
We plan to use the data from the study to write 2-3 manuscripts.  Initially, since this is a relatively 
novel approach to the resection of bladder tumors, we plan to report the technique for 
dissemination among the urologic community.  Once the study concludes, we would then plan on 
writing at least one manuscript detailing the intra-operative/peri-operative, oncologic, and 
histopathologic results of the study.  Depending on the robustness of the data, a second manuscript 
could be prepared describing post-operative urinary bother between the two groups combined with 
thermal spread/cautery artifact data. 
 
16. IRB 
This protocol and study will be submitted for IRB approval.   
 
Any adverse events, protocol deviations, or reportable events will be reported to the IRB promptly 
and followed-up by investigators until resolved or stable. 
 
17. Informed Consent 
Consent will be obtained from each patient included in the study.  Approval of a consent form by 
the patient will be required and will be documented prior to inclusion in the study. 
 
Investigator will disclose any financial interests with Olympus or any other contributor during the 
course of the study.   
 
18. Monitoring Procedures 
 
The safety of the TURBT Button Vaporization technique will be monitored during the study on a 
regular basis by the study coordinators.  Also, all other documentation required by part of the 
investigation should be monitored.  This may include informed consent documents, patient case 
history files, enrollment questionnaires (inclusion/exclusion criteria is assessed), case report forms, 
adverse event report forms, post-op test results and questionnaires (these will be followed per 
protocol). 
 
Appendices 
The following will be provided by the principal investigator prior to the start of the study: 
 
  Patient Consent Form.  
  Patient Data Sheet 
Approval: 
  Senior Management of QA/RA 
  Responsible Marketing Manager 

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  Investigator 
  Participating IRB(s) 
 
                                                 
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based on November 2010 SEER data submission, posted to the SEER web site, 2011. 
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Management of Nonmuscle Invasive Bladder Cancer (Stages Ta, T1, and Tis), Chapter 1- Diagnosis and Treatment 
Options: 2007 Update. American Urological Association Education and Research, Inc. 2007; 15:51.  
 
iii Issa MM. Technological advances in transurethral resection of the prostate: bipolar versus monopolar TURP. J 
Endourol. 2008;22:1587–1595. 
 
iv Bipolar transurethral resection of prostate: Current status in the management of bladder outflow obstruction..Bolgeri M, Naji S, Sahai A, et al. 
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