Evaluation of the Off-Clamp Robot-Assisted Partial Nephrectomy Technique in the Management of Renal Tumors
Phase: NA
Conditions: Renal Cancer, Renal Ischemia
Sponsor: Washington University School of Medicine

 
 
Official Title:  
Evaluation of the Off‐Clamp Robot‐Assisted Partial  
 
 
 
 
 
Nephrectomy Technique in the Management of Renal Tumors 
 
 
 
NCT Number: 
NCT01732120 
 
Document date:  01 May 2015 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Evaluation of the Off‐Clamp Robot‐Assisted Partial Nephrectomy 
Technique in the Management of Renal Tumors 
 
 
 
 
 
 
Washington University School of Medicine 
Department of Surgery 
660 S. Euclid Ave., Campus Box 8109 
St. Louis, MO 63110 
 
 
 
Protocol v6 
Version date: 05/01/15 
 
 
 
Principal Investigator: 
R. Sherburne Figenshau, M.D. 
Phone:  
 
 
(314) 454-2235 
Email:  
 
 
figenshaur@wudosis.wustl.edu 
 
 
 
 
 
 
 
 

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Evaluation of the Off-Clamp Robot-Assisted Partial Nephrectomy Technique 
in the Management of Renal Tumors 
 
TREATMENT SCHEMA 
 
 
Eligible Patients 
1.  Patients 18 and older. 
2.  Patients willing and able to sign consent. 
3.  Patients with an organ confined renal mass planning to undergo a 
robotic assisted partial nephrectomy (RAPN). 
4.  Patient with Karnofsky Performance Status (KPS) equal to or greater 
than 40. 
Pre-Enrollment Evaluation 
H&P including ht &wt, Serum Creatinine/eGFR 
Review of abdominal MRI or CT scan,   
Renal Scan and CXR 
 
Enrollment 
Pre-Randomization Evaluation 
Laparoscopy with intra-operative evaluation by the surgeon (if still 
candidate for study, proceed to randomization and intervention) 
 
Ready for Intervention 
Intervention 
RAPN off-clamp vs traditional hilar clamping 
Post-Intervention Monitoring 
Standard post-operative recovery 
Follow-up 
Day 1 post RAPN: Serum Creatinine/eGFR 
Month 3 post RAPN: H&P, Serum Creatinine/eGFR, renal scan, CT/MRI, 
CXR, AE assessment 
Every 12 months (For patients with malignant pathological outcome): 
Serum Creatinine/eGFR, CT/MRI, CXR  

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Evaluation of the Off-Clamp Robot-Assisted Partial Nephrectomy Technique in the 
Management of Renal Tumors 
 
TREATMENT SCHEMA ............................................................................................................................. 2 
1.0 
BACKGROUND AND RATIONALE ............................................................................................. 4 
2.0 
OBJECTIVES ................................................................................................................................... 5 
3.0 
PATIENT SELECTION ................................................................................................................... 6 
4.0 
REGISTRATION PROCEDURES................................................................................................... 6 
5.0 
TREATMENT PLAN ....................................................................................................................... 7 
6.0 
ADVERSE EVENT REPORTING ................................................................................................. 10 
7.0 
DATA SUBMISSION SCHEDULE ............................................................................................... 11 
8.0 
DATA AND SAFETY MONITORING ......................................................................................... 11 
9.0 
STATISTICAL CONSIDERATIONS ............................................................................................ 12 
10.0 
REFERENCES ............................................................................................................................... 14 
APPENDIX A: Karnofsky Performance Scale ................................................................................................ 16 
APPENDIX B: The Clavien-Dindo Classification of Surgical Complications .................................................. 17 
APPENDIX C: Study Schedule of Events ...................................................................................................... 18 
 
 
 

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1.0 
BACKGROUND AND RATIONALE 
 
1.1 
Study Disease 
 
Due in part to the widespread use of abdominal imaging procedures, the incidence of renal tumors 
has incremented exponentially over the last several decades [1]. The National Cancer Institute 
estimates the incidence of new cases of renal cell carcinoma in 2011 at 60,920 [2]. The increasing 
detection of incidental small renal masses on abdominal imaging has been accompanied by a clear 
downward stage migration, such that by 2007, close to 60% of renal tumors measured < 4 cm [3, 
4]. Indeed, about 50% of the patients referred to urologists today for suspected renal malignancy 
have incidentally discovered asymptomatic small renal masses [5]. 
Importantly, the highest incidence of these tumors is seen in elderly patients, who usually present 
with a number of comorbidities[6]. In treating patients with renal masses, three competing factors 
have to be balanced:  cancer control, patient morbidity, and preservation of renal function.  
Preservation of renal function is a key factor in survival. With mounting evidence highlighting the 
importance of renal preservation [7-10] and documentation of the oncologic efficacy of partial 
nephrectomy [11], the American Urological Association’s guidelines currently place partial 
nephrectomy as the standard of care for the management of T1a tumors (< 4 cm) and as an 
alternative treatment option for T1b tumors (4-7 cm) [12].  Reflecting this paradigm shift, the use 
of partial nephrectomy has risen substantially at many centers of excellence over the past decade, 
approaching 90% for T1a tumors [13]. 
With evidence demonstrating improved patient survival following partial rather than radical 
nephrectomy, nephron-sparing surgery (NSS) has become the standard of care for the management 
of T1a renal tumors and an accepted alternative for the management of T1b tumors [14, 15].  
Furthermore, as the use of minimally invasive technology has advanced within the urologic 
community, laparoscopic partial nephrectomy and robot-assisted partial nephrectomy (RAPN) 
have been established as viable alternatives to open NSS [16, 17].   
Open NSS traditionally involves clamping of the renal hilar vessels and an abundant use of ice to 
ensure tissue hypothermia.  However, techniques of achieving kidney hypothermia have not been 
translated to minimally invasive NSS.  Thus, renal hilar clamping during minimally invasive NSS 
is performed under warm ischemia.  Increased duration of warm ischemia time (WIT) has been 
demonstrated to negatively impact short and long-term renal function [18].  As a result, many 
techniques for limiting WIT have been described, including segmental renal artery clamping, renal 
parenchymal clamping, early unclamping, and unclamped NSS following administration of 
hypotensive agents [19-22].  
  

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Several years ago, the Principal Investigator developed a technique where RAPN is performed 
without clamping of the renal hilar vessels and without systemic blood pressure manipulation.  
This technique is applicable to all renal tumors that are appropriate for partial nephrectomy.  
In order to determine the efficacy of this procedure, a retrospective chart review, matched cohort 
study was performed at Washington University comparing 29 patients who underwent off-clamp 
RAPN for suspected renal cell carcinoma with a matched 29 patients that underwent RAPN with 
hilar clamping. The procedures were performed from 3/2008 to 9/2011, and the patients in each 
group were similar in nephrometry score and baseline renal function.  The off-clamp patients 
experienced an estimated blood loss of 146.4cc, while the hilar clamped RAPN group had an 
estimated blood loss of 103.9cc (p=0.039).  The complications were similar in the two groups with 
no complications seen in the off-clamp group and only one Clavien-2 complication in the hilar 
clamp group.  The mean eGFR decline was 4.9 ml/min/1.73m2 in the off-clamp group and 
11.7ml/min/1.73m2 in the hilar clamp group (p=0.033).  In summary, the off-clamp RAPN patients 
experienced less decline in renal function while experiencing similar morbidity [23].  
These preliminary results have shown comparable perioperative outcomes to traditional clamped 
RAPN, while mitigating renal functional damage and providing excellent oncologic control.  To 
date, we have submitted for publication: 1) video and detailed description of our off-clamp RAPN 
technique, 2) safety and efficacy of this technique in our initial 42 patient experience, 3) safety 
and efficacy of our technique for technically difficult renal tumors, and 4) a retrospective matched 
cohort study comparing off-clamp to clamped RAPN.  We aim to prospectively compare renal 
functional, perioperative and oncologic outcomes between our off-clamp technique and traditional 
clamped RAPN.   
1.2 
Rationale 
 
Randomizing patients to either traditional clamped RAPN or off-clamp technique will allow for 
prospective data in regards to the effect of hilar clamping on renal function. We hypothesize that 
the off-clamp RAPN technique will lead to decreased decline in renal function compared to the 
on-clamp RAPN.   
 
2.0 
OBJECTIVES 
 
2.1 
Primary Objective 
 
1. To determine if off-clamp RAPN technique better preserves long-term renal function 
than the traditional clamped RAPN technique. 
 
2.2 
Secondary Objectives 
 
1. To determine if oncologic outcomes are equivalent between off-clamp and traditional 
clamped RAPN. 
 
2. To determine if the complication severity and rates are equivalent between off-clamp 

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technique and traditional clamped RAPN. 
 
3. To determine if off-clamp RAPN technique requires longer operative times or 
prolongs hospital stay. 
 
4. To determine if off-clamp RAPN technique causes greater blood loss during surgery. 
 
 
3.0 
PATIENT SELECTION 
 
3.1 
Inclusion Criteria 
1.  Patients 18 and older. 
2.  Patients willing and able to sign consent. 
3.  Patients with an organ confined renal mass planning to undergo a robotic assisted 
partial nephrectomy (RAPN). 
4.  Patient with Karnofsky Performance Status (KPS) equal to or greater than 40. 
 
3.2 
Exclusion Criteria 
 
1.  Patients under 18. 
2.  Patients with Karnofsky Performance Status (KPS) less than 40. 
3.  Patients with non-organ confined renal masses (invading renal vein, inferior vena                     
cava, peri-renal tissue, ipsilateral adrenal gland, or metastasis). 
4.  Patients with bilateral synchronous renal masses. 
5.  Patients who can not discontinue, Plavix, Coumadin or other anti-platelet or anti-
coagulant medications.  
6.  Patients with renal lesions determined to be too complex to perform a RAPN without 
clamp by the surgeon. (The renal mass may be deemed too difficult based on pre-
operatively radiological findings. The surgeon’s decision to exclude a mass from a 
robotic assisted partial nephrectomy would be based on a higher risk of positive 
margin or complication if a RAPN was performed.) 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this 
trial. 
 
 
4.0 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the 
Siteman Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility  
2. Registration of patient in the Siteman Cancer Center database 
3. Assignment of unique patient number (UPN) 

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4.1 
Confirmation of Patient Eligibility 
 
The following information is required to confirm patient eligibility prior to registering 
patient: 
 
1. Registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form 
5. Planned date of enrollment 
6. Completed eligibility checklist, signed and dated by a member of the study team 
7. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center Database 
 
All patients must be registered through the Siteman Cancer Center database (SCCdb). 
 
4.3 
Assignment of UPN 
 
For the purpose of this study, each patient will be identified with a unique patient number 
(UPN) which will be assigned consecutively at the time of registration in the SCCdb.        
All data will be recorded with this identification number on the appropriate CRFs.  The 
UPN will not include the patient’s initials as this is considered identifiable information per 
Siteman Cancer Center Guidelines. 
 
 
5.0 
TREATMENT PLAN 
 
5.1 
Preoperative Evaluation 
 
Patients will be evaluated to determine whether they meet the criteria specified in 
Section 3.1.  Patients meeting these criteria will continue to next step. 
 
Patients   will   have   standard   of   care blood work which will include serum creatinine, 
preoperatively. Tumor characteristics based on preoperative cross-sectional imaging will be 
recorded, particularly components of the nephrometry score. 
  
5.2 
Operative Procedure 
 
5.2.1. Randomization 
Randomization will take place in the operating room, after feasibility of RAPN off clamp 
is confirmed.  Patients will be randomized to either off-clamp RAPN or traditional clamped 
RAPN in a 1:1 ratio, for a total of 40 patients allocated to each group.  To minimize 
selection bias, a randomization table will be developed before initiation of enrollment. 

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Envelopes containing randomization assignments will be created, sequentially numbered 
and sealed.  Once enrollment is initiated, randomization envelopes will be opened for each 
subject after informed consent is granted and study eligibility is confirmed in the operating 
room. 
5.2.2. Day of surgery 
 
Standard preoperative and perioperative procedures for RAPN will be followed in both 
groups.  For the control group (traditional clamped technique), RAPN will be performed 
in the standard fashion.  For the treatment group (off-clamp technique), RAPN will be 
performed with our off-clamp technique.  There is also a possible chance the procedure 
may be switched intraoperatively due to a variety of factors. For example, intraoperatively 
a patient undergoing a RAPN off-clamp may require emergent conversion to a traditional 
hilar clamped RAPN for excessive bleeding. Also, a patient undergoing either RAPN off-
clamp or traditional hilar clamped RAPN could require conversion to either open partial 
nephrectomy, open radical nephrectomy, or laparoscopic radical nephrectomy given 
intraoperative conditions. A change in technique would only take place if required to 
maintain patient safety.  
 
5.2.3. Description of the off-clamp RAPN technique        
         
In the off-clamp RAPN technique, after surgical access is gained, kidney is mobilized and 
Gerota’s fascia is incised. The perinephric fat is dissected away from the renal capsule to 
expose the tumor.  
Intravenous mannitol (12.5 grams) is administered by anesthesia. Two robotic bulldog 
clamps are introduced to allow for expeditious clamping of the hilum if necessary. The 
margins of the mass are outlined circumferentially with monopolar electrocautery on the 
robotic scissors. This cautery is continued until an appropriate plane of dissection is found. 
Forceps are used to bluntly separate the tumor from the residual renal parenchyma with 
intervening tissue cauterized meticulously with the monopolar scissors. If a large vessel 
from the renal parenchyma is noted to be bleeding during tumor excision, the robotic 
bulldogs can be applied to the vessel in the resection bed. This controls the bleeding 
vessel(s) until suture ligation or clip application of the vessel(s) can be performed.  
Additionally, larger vessels that are directly supplying the tumor can be controlled with 
clips if hemostasis with cautery is not adequate. Mobilization of the tumor is continued 
circumferentially until complete excision of the tumor is achieved. The bedside assistant 
uses suction and applies countertraction as necessary during tumor excision. The specimen 
is then placed above the liver or spleen for later retrieval. 
The base of the resection bed is cauterized. The insufflation pressure of the 

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pneumoperitoneum is decreased and the resection bed is examined for any ongoing 
bleeding. 
Any patent venous sinuses or arteries at the base of the resection are oversewn. If the 
collecting system has been entered, it is similarly closed. The defect in the renal 
parenchyma is closed using a sliding clip renorrhaphy technique.  Gerota’s fascia is then 
similarly reapproximated. 
The specimen is entrapped in a specimen bag and then the robot is undocked. The specimen 
is removed through a port site with extension of the incision as necessary. 
The fascia for the ports is closed and skin is reapproximated. 
5.3 
Risks of RAPN 
There are multiple potential risks associated with a RAPN.  Complications include but are 
not limited to the following: hemorrhage requiring transfusion, urinary leak/fistula, 
abscess, loss of renal function, injury to surrounding organs, conversion to an open surgery, 
conversion to a radical nephrectomy, incisional hernia, deep venous thrombosis, 
pulmonary embolism, myocardial infarction, stroke, and death. 
A recent multi-institutional study reported complication rates for 450 RAPN procedures.  
The overall complication rate was 15.8% with 76.1% Clavien grade I-II and 23.9% Clavien 
grade III-IV.  Hemorrhage requiring a transfusion occurred in 5.1% and arterial 
embolization to stop hemorrhage in 0.4%.  A urine leak occurred in 1.6% with no patient 
requiring explorative operations for urinary leak.  Intra-operative conversion to radical 
nephrectomy occurred in 1.6%.  No deaths occurred in the 450 cases. 
 
5.4 
Postoperative Care 
 
The postoperative management is standard of care for all patients who undergo RAPN. 
 
 
 
                          Three month post op visit: 
• CR/eGFR 
• Renal Scan 
• CT/MRI of abdomen 
• Chest x-ray (CXR) 
 
 
 
5.5 
Duration of Follow-Up 
 
The follow up management is standard of care but uniquely different for patients based on 
pathologic outcome.  Patients with a malignant (cancerous) surgical pathology will be 
followed for a period of 3 years.  Patients with a benign (non-cancerous) surgical pathology 
will only be followed through a period of 3 months postoperatively.  Patients removed from 

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this study for unacceptable adverse events will be followed until resolution or 
stabilization of the adverse event. 
 
   Yearly follow up visits: 
• CR/eGFR 
• CT/MRI of abdomen 
• Chest x-ray (CXR) 
 
 
5.6 
Criteria for Removal from Study 
 
If at any time the constraints of this protocol are considered to be detrimental to the 
patient’s health and/or the patient no longer wishes to proceed with the protocol 
intervention, the patient should be removed from the study and the reason(s) for 
discontinuation documented in the case report forms. 
 
Otherwise, the patient will receive the intervention and be followed as described. 
 
 
6.0 
ADVERSE EVENT REPORTING 
 
6.1 
Adverse Events 
 
Definition: any unfavorable medical occurrence in a human subject including any 
abnormal sign, symptom, or disease. 
 
Grading: the descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all 
toxicity reporting.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP 
website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms 
listed that should be used are those provided by the Department of Health and Human 
Services’ Office for Human Research Protections (OHRP).  A copy of this guidance can 
be found on OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
All HRPO guidelines for reporting unanticipated problems will be followed. 
 
6.2 
Measurement of Post-Operative Complications 
 
In addition to reporting AEs according to the CTCAE (as described in Section 6.1), 
postoperative complications will be reported using the Clavien-Dindo 
Classification of Surgical Complications Appendix B. Adverse Events and 
Complications will be assessed from time of study intervention to the three month 
post visit.  
 
The principal investigator will also determine complications based on normal standards.  

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Complication Examples: 
1. Intra-operative complications for a RAPN include but are not limited to injury 
to the surrounding organs and vessels, excessive blood loss requiring blood 
transfusions, and conversion to radical nephrectomy or open surgery. 
 
2. Postoperative complications for RAPN include but are not limited to urine leak, 
urinoma, abscess, pseudoaneurysm, ileus, blood transfusion requirements, 
incisional hernias, wound infection, blood transfusion requirements, deep 
venous thrombosis, pulmonary embolism, myocardial infarction, stroke, and 
death. 
 
 
7.0 
DATA SUBMISSION SCHEDULE 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
Eligibility Checklist  
Prior to starting treatment 
Baseline Data Sheet 
Following receipt of pathology report 
Adverse Event/Complication 
Assessment 
Baseline,  and 3 months after surgery 
and at the time of any complication 
Follow-Up Data Sheet 
3 months after surgery then annually 
thereafter 
SAE Reporting Form 
At the time of any SAE 
 
 
8.0 
DATA AND SAFETY MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring 
Plan, the Principal Investigator will provide a Data and Safety Monitoring (DSM) report 
to the Washington University Quality Assurance and Safety Monitoring Committee 
(QASMC) semi-annually beginning six months after accrual has opened (if at least five 
patients have been enrolled) or one year after accrual has opened (if fewer than five patients 
have been enrolled at the six-month mark). 
 
The Principal Investigator will review all patient data on an ongoing basis and provide a 
semi- annual report to the Quality Assurance and Safety Monitoring (QASM) Committee.  
This report will include: 
 
• HRPO protocol number, protocol title, Principal Investigator name, data 
coordinator name, regulatory coordinator name, and statistician 
• Date of initial HRPO approval, date of most recent consent HRPO 
approval/revision, date of HRPO expiration, date of most recent QA audit, 
study status, and phase of study 

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• History of study including summary of substantive amendments; summary 
of accrual suspensions including start/stop dates and reason; and summary 
of protocol exceptions, error, or breach of confidentiality including 
start/stop dates and reason 
• Study-wide target accrual and study-wide actual accrual 
• Protocol activation date 
• Average rate of accrual observed in year 1, year 2, and subsequent years 
• Expected accrual end date 
• Objectives of protocol with supporting data and list the number of 
participants who have met each objective 
• Measures of efficacy 
• Early stopping rules with supporting data and list the number of participants 
who have met the early stopping rules 
• Summary of toxicities 
• Abstract submissions/publications 
• Summary of any recent literature that may affect the safety or ethics of the 
study  
 
The study principal investigator and research patient coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or research patient 
coordinator becomes aware of a serious adverse event, the SAE will be reported to the 
HRPO and QASM Committee according to institutional guidelines. 
 
 
9.0 
STATISTICAL CONSIDERATIONS 
 
9.1 
Study Objectives and Endpoints 
 Primary Outcome: 
Evaluation of renal function following RAPN with or without hilar clamping 
using:  
1. Decline in estimated glomerular filtration rate (eGFR). eGFR is calculated from 
serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration 
formula [11].  Decline in eGFR = Postoperative eGFR – Preoperative eGFR. 
2. Decline in split renal function (SRF). SRF is a percentage of the total renal 
function supplied by one kidney.  Ideally each kidney has a SFR of 50%.  SRF is 
measured during renal scintigraphy (renal scan).  Decline is SRF =preoperative 
SRF- postoperative SRF (3 month). 
 
 Secondary Outcomes: 
      1.   Oncological outcomes: 
a. Pathological results 
 
 
1. Pathologic margin status 
 
 
2. Tumor histology, including Fuhrman grade if applicable 
 
 
3. Distance between tumor margin and surgical margin 

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                  b. Evidence of disease recurrence or metastasis on follow-up imaging  
 
             1. Recurrence free survival 
      
       2.   Perioperative outcomes 
 
       
a. Estimated blood loss 
b. Operative time and warm ischemia time 
c. Intra-operative complications, including but not limited to injury to the 
surrounding organs and vessels, excessive blood loss requiring blood 
transfusions, and conversion to radical nephrectomy or open surgery. 
d. Length of postoperative hospital stay 
e. Postoperative complications, including but not limited to urine leak, 
urinoma, abscess, pseudoaneurysm, ileus, blood transfusion requirements, 
incisional hernias, wound infection, blood transfusion requirements, deep 
venous thrombosis, pulmonary embolism, myocardial infarction, stroke, and 
death. 
   
 
9.2 
Study Design 
This is a single institution, prospective, randomized, controlled study to evaluate the off-
clamp RAPN technique.  Parallel group design with randomization allocation ratio of 1:1 
to off-clamp RAPN technique (study treatment) and traditional clamped RAPN technique 
(control) will be utilized.  Study will be conducted at Washington University and will enroll 
approximately 80 participants over the course of the study. 
 
9.3 
Data Analysis 
 
Data analysis for this study will be descriptive in nature. Demographic and clinical 
characteristics of the sample, as well as local recurrence and post-surgery complications 
will be summarized using descriptive statistics. Kaplan-Meier product limit method will 
be used to estimate the 2-year overall and disease-free survival. The median disease-free 
survival, overall survival and their 95% confidence interval will also be estimated.  
  
 
 

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10.0 
REFERENCES 
 
 
1. Chow WH, Deresa SS, Warren JL, et al: Rising incidence of renal cell cancer in the 
United States. JAMA 1999; 281: 1628-1631. 
2. National Cancer Institute at the National Institute of Health.  Kidney Cancer- Estimated 
new cases and deaths.  (http://www.cancer.gov/cancertopics/types/kidney) 
3. Kane CJ, Mallin K, Ritchey J, et al:  Renal cell cancer stage migration:  analysis of the 
National Cancer Data Base.  Cancer 2008; 113: 78. 
4. Cooperberg MR, Mallin K, Kane CJ, et al:  Treatment trends for stage I renal cell 
carcinoma.  J Urol 2011; 186(2): 394-9. 
5. Miller DC, Ruterbusch J, Colt JS, et al:  Contemporary clinical epidemiology of renal cell 
carcinoma:  insight from a population based case-control study.  J Urol 2010; 184: 2254-
8. 
6. Jewett MAS, Mattar K, Basiuk J, et al:  Active surveillance of small renal masses: 
progression patterns of early stage kidney cancer.  Eur Urol 2011; 60: 39-44. 
7. Go AS, Chertow GM, Fan D, et al:  Chronic kidney disease and the risks of death, 
cardiovascular events, and hospitalization.  NEJM 2004; 351: 1296-1305. 
8. Huang WC, Levey AS, Serio AM, et al: Chronic kidney disease after nephrectomy in 
patients with renal cortical tumors:  a retrospective cohort study.  Lancet Oncol 2006; 7: 
735-740. 
9. Thompson RH, Boorjian SA, Lohse CM, et al: Radical nephrectomy for pT1a renal 
masses may be associated with decreased overall survival compared with partial 
nephrectomy.  Cancer 2008; 112: 511-520. 
10. Weight CJ, Lieser G, Larson BT, et al:  Partial nephrectomy is associated with improved 
overall survival compared to radical nephrectomy in patients with unanticipated benign 
renal tumors.  Eur Urol 2010; 58(2): 293-8. 
11. Fergany A.F, Hafez KS, and Novick AC: Long-term results of nephron sparing surgery 
for localized renal cell carcinoma: 10-year followup.  J Urol 2000; 163: 442. 
12. Campbell SC, Novick AC, Belldegrun A, et al:  Practice Guidelines Committee of the 
American Urological Association.  Guidelines for management of the clinical T1 renal 
mass.  J Urol 2009; 182:1271-9. 
13. Clark PE, Schover LR, Uzzo RG, et al:  Quality of life and psychological adaptation after 
surgical treatment for localized renal cell carcinoma:  impact of the amount of remaining 
renal tissue.  Urology 2001; 57: 252. 
14. Thompson RH, Boorjian SA, Lohse CM, et al.  Radical nephrectomy for pT1a renal 
masses may be associated with decreased overall survival compared with partial 
nephrectomy.  Cancer 2008; 122: 511-520.  
15. American Urological Association Education and Research (AUA) Guidelines: 
“Guidelines for Management of the Clinical Stage I Renal Mass.” Renal Mass Clinical 

Figenshau  
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05.01.15 
Panel Chairs:  Novick AC (Chair), Campbell SC (Co-Chair): 
www.auanet.org/content/media/renalmass09.pdf 
16. Gill IS, Kavoussi LR, Lane BR, et al.  Comparison of 1,800 laparoscopic and open partial 
nephrectomies for single renal tumors.  J Urol 2007; 178: 41-46.  
17. Benway BM, Bhayani SB, Rogers CG, et al.  Robot assisted partial nephrectomy versus 
laparoscopic partial nephrectomy for renal tumors: a multi-institutional analysis of 
perioperative outcomes.  J Urol 2009; 182: 866-873. 
18. Every minute counts when the renal hilum is clamped during partial nephrectomy.  
Thompson RH, Lane BR, Lohse CM, Leibovich BC, Fergany A, Frank I, Gill IS, Blute 
ML, Campbell SC. Eur Urol. 2010 Sep;58(3):340-5. 
19. Figenshau RS.  Laparoscopic partial nephrectomy with segmental renal vascular control.  
J Endourol 2005; 19 (supplement 1): A257. 
20. Viprakasit DP, Altamar HO, Miller NL, and Herrell SD.  Selective renal parenchymal 
clamping in robotic partial nephrectomy:  initial experience.  Urology 2010; 76: 750-753. 
21. San Francisco IF, Sweeney MC and Wagner AA.  Robot-assisted partial nephrectomy:  
early unclamping technique.  J Endourol 2011; 25: 305-308. 
22. Gill IS, Eisenberg MS, Aron M et al.  ‘Zero ischemia’ partial nephrectomy:  novel 
laparoscopic and robotic technique.  Eur Urol 2011; 59: 128-134. 
23. Tanagho Y, Bhayani S, Sandhu G, Vaughn N, Nepple K, Figenshau R.  Renal Functional 
and Perioperative Outcomes of Off-Clamp vs. Clamped Robot-Assisted Partial 
nephrectomy:  Matched Cohort Study.  (Accepted for publication in Urology) 
24. Kutikov A and Uzzo RG.  The RENAL nephrometry score: a comprehensive 
standardized system for quantitating renal tumor size, location and depth.  J Urol 2009; 
182: 844-853. 
25. Levey AS, Stevens LA, Schmid CH, et al.  A new equation to estimate glomerular 
filtration rate.  Ann Intern Med 2009; 150: 604-612.  
26. Spana G, Haber G, Dulabon L, Petros F, Rogers C, Bhayani S, Stifelman M, and 
Kaouk J. Complications after robotic partial nephrectomy at centers of excellence: a 
multi-institutional analysis of 450 cases. J Urol. 186: 417-422. 
 
    

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APPENDIX A: Karnofsky Performance Scale 
 
Description 
Percent (%) 
Normal; no complaints; no evidence of disease 
100 
Able to carry on normal activity; minor signs and 
symptoms of disease 
90 
Normal activity with effort; some signs and symptoms of 
Disease 
80 
Cares for self; unable to carry on normal activity or do 
Work 
70 
Requires occasional assistance, but is able to care for 
most personal needs 
60 
Requires considerable assistance and frequent medical 
Care 
50 
Disabled; requires special care and assistance 
40 
Severely disabled; hospitalization indicated although 
death not imminent 
30 
Very sick; hospitalization necessary; requires active 
support treatment 
20 
Moribund; fatal processes progressing rapidly 
10 
Dead 
0 

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APPENDIX B: The Clavien-Dindo Classification of Surgical Complications 
 
Full Scale  
 
Contracted Form  
Grades  
Definition  
Grades 
Definition 
Grade  I:  
Any deviation from the normal 
postoperative course without the need for 
pharmacological treatment or surgical, 
endoscopic and radiological interventions.  
 Grade  I:  
Same as for Full Scale 
Allowed therapeutic regimens are: drugs as 
antiemetics, antipyretics, analgetics, 
diuretics and electrolytes and 
physiotherapy. This grade also includes 
wound infections opened at the bedside.  
 
Grade  II:  Requiring pharmacological treatment with 
drugs other than such allowed for grade I 
complications. 
Blood transfusions and total parenteral 
nutrition are also included.  
 Grade  II: Same as for Full Scale 
 
Grade  III:  Requiring surgical, endoscopic or 
radiological intervention  
 Grade  III:  
 
Grades IIIa & IIIb  
Grade III-a: intervention not under general anesthesia  
Grade III-b: intervention under general anesthesia  
 
Grade IV:  Life-threatening complication (including 
CNS complications)‡ requiring IC/ICU-
management  
 Grade IV:  Grades IVa & IVb  
Grade IV-a: single organ dysfunction (including 
dialysis)  
Grade IV-b: multi organ dysfunction  
 
Grade V:  
Death of a patient  
 Grade V:  Same as for Full Scale 
Suffix 'd':  If the patients suffers from a complication 
at the time of discharge,  the 
suffix  “d”  (for ‘disability’) is added to the 
respective grade of complication. This label 
indicates the need for a follow-up to fully 
evaluate the complication.  
 
 
 
‡ brain hemorrhage, ischemic stroke, subarrachnoidal bleeding,but excluding transient ischemic attacks (TIA);IC: 
Intermediate care; ICU: Intensive care unit. 
Dindo D., Demartines N., Clavien P.A.; Ann Surg. 2004; 244: 931-937 

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APPENDIX C: Study Schedule of Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
Scans (Renal Scan, CT/MRI of abdomen and Chest Xray (CXR)) performed prior to or at time of baseline assessments per standard of care  
2 
From the date of 3-mo follow up for total of 3 years only for patients with malignant pathological outcome  
 
Pre-Operative 
Assessments 
Surgery 
Post-Operative Assessments 
 
Baseline1 
 
RAPN 
 
1 day 
Post RAPN 
3 months 
Post RAPN 
 
Every 12 months2 
 
Informed Consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical & Surgical History 
X 
 
 
 
 
Height & Weight 
X 
 
 
 
 
Serum Creatinine/eGFR 
X 
 
X 
X 
X 
Renal Scan 
X1 
 
 
X 
 
CT/MRI of abdomen 
X1 
 
 
X 
X 
CXR 
X1 
 
 
X 
X 
Incl./Excl. Criteria Confirmation 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
Perioperative Outcomes 
 
X 
 
 
 
Pathology results 
 
X 
 
 
 
Adverse Event Assessment 
 
 
 
X 
 
Assessment of Evidence of Disease 
Recurrence 
 
 
 
X 
X