Tamer Abou Youssif

26/4/2008

1
 Surgical resection remains the
cornerstone of treatment for RCC.

 ORN was the ‘gold standard’ of care

for localized RCC against which all
other forms of surgery for RCC were
measured.

 This standard has been challenged

by the introduction of elective NSS
for SRMs 2
3
Pantuck, A. J., Zisman, A., Belldegrun, A. S.: The changing natural history of
renal cell carcinoma. J Urol, 166: 1611, 2001

4
  Increase in survival after RN is true,
whereas increase in survival due to
imaging is false
length bias lead-time bias

5
 We are now sparing more adrenal glands, as
adrenalectomy with RN is no longer necessary
for most tumors

 Unconditional ipsilateral adrenalectomy with

radical nephrectomy for RCC should be
avoided (poor response to the rapid ACTH
stimulation test )

 Preoperative efficacy of CT is effective in

predicting adrenal involvement with sensitivity
and specificity of 87.5–100% and 76–98%,
respectively.
6
 Lymphadenectomy in the treatment of RCC is
controversial, but the prognostic role is
without question.

Pantuck, A. J., Zisman, A., Dorey, F. et al.: Renal cell carcinoma with retroperitoneal
lymph nodes: role of lymph node dissection. J Urol, 169: 2076, 2003
7
 Patients with micrometastatic lymph
node involvement (4.7%) who might
benefit from prophylactic
lymphadenectomy.
 30% of patients with enlarged LNs on
CT might have inflammatory nodal
enlargement only.
 EORTC 30881 ,A prospective
randomized controlled study , failed to
show a survival difference between
patients treated with and without lymph
node dissection at the 5-year follow-up
8
9
Schlichter et al*
 372 RN specimens.
 The nephrectomy specimens were cut into 3-
mm sections
 Cytogenetic and molecular genetic studies
were also performed
 92 multifocal lesions were found in 61
specimens (16.4%)
 Multifocality was independent of primary
tumor size
 1/3 of all cases demonstrated concordance
regarding chromosomal aberrations between
the primary and secondary tumors 10
Kletscher et al prospective study**
 100 RN specimens with localized RCC.
 preoperative CT /MRI, standard pathologic
examination , and 3-mm step-sectioning
under magnification were done.
 Multifocal RCC was found in 16 specimens.
 Imaging studies suggested multifocal cancer
in 7/16 cases (44%).
 Standard pathology techniques identified
multifocal cancer in 10 /16 specimens (63%).

11
 Papillary and mixed histologic patterns
occurred at a significantly increased rate in
specimens with multifocal disease (P .011).
 Tumor size and volume, histologic grade, and
DNA ploidy did NOT correlate with the
presence or extent of multifocality
 Risk of unknown multifocality in a surgical
setting seems to be 6% that corresponds to
the incidence of locally recurrent disease in
published large series of NSS.

Kletscher BA, Qian J, Bostwick DG, et al: Prospective analysis of multifocality in renal cell
carcinoma: Influence of histological pattern, grade, number, size, volume and
deoxyribonucleic acid ploidy. J Urol 153:904-906, 1995

12
 Kidney donors as well as RN patients
both scarify a renal unit
 Patients undergoing donor
nephrectomy
 minimal adverse effects on overall
health status
 ↑ GFR with consequent ↑ in renal length
 In long-term follow-up renal function is
well preserved
 no evidence of progressive renal
deterioration or other serious disorders
 GFR ↓with age as individuals with two 13
 LRN has emerged as a less morbid
alternative to ORN
 LRN is associated with
 Diminished postoperative discomfort
 Shortened recovery
 CSS after LRN is comparable to that
after ORN

14
15
 Interest in elective NSS
stimulated by
Shiftin RCC stage and size
Risk of benign tumors in SRMs

Good long-term survival

Preservation of Renal Function

16
 The introduction and mainstream use of
abdominal CT and US has resulted in an
increase in the incidental detection of
RCC in asymptomatic patients.

 70% of the tumors are detected

incidentally with a median tumor size of
below 4.0 cm.

 16.4 -23% of patients following surgical

resection of a SRM will have a benign
lesion. 17
18
Frank et al, 2003 ( a frequently cited article)
 2,770 adult patients who underwent RN or
NSS
 376 benign (12.8%) and 2,559 (87.2%)
malignant tumors
 98% of RCC tumors less than 1 cm were low
grade RCC
 The odds of having a malignant compared to a
benign tumor ↑ Less than 1
significantly More than 7
as tumor size ↑
Benign cm
43.3% cm
6.3%
(p 0.001, OR 1.17 , CI 1.08–1.26).
tumors
Clear cell 25.6% 83%
HighRCC
grade 2.3% 57.7%
RCC
19
 With each 1 cm increase there is
 17% increase in the odds of
malignancy
 32% increase in the odds of high
grade RCC
 These data provide a pathological basis
for the use of
 Minimally invasive techniques in the
treatment of SRMs
 Conservative management in select
cases.
20
Dechet et al studied the accuracy of
frozen section pathology for needle
biopsy of renal tumors
prospective analysis of 106 renal masses.
Each specimen was examined by two urologic
pathologists blinded to final pathology
15 lesions were considered benign after formal
final pathologic review
one pathologist read 3/15 needle biopsies as
malignant, while the other read 5/15 needle
biopsies as malignant
Both pathologists read 4/91 needle biopsies as
benign lesions
21
 100 patients with solid renal masses in which
role of renal biopsy and imaging were studied
 Final pathology: 85 lesions malignant and 15
lesions benign
 Sensitivity and specificity of CT imaging were
74% and 20%, respectively.
 Sensitivity and specificity of biopsy were 81%
and 60% for one pathologist and 83% and
33% for the other.
 Imaging was considered non diagnostic in
31% of cases for one radiologist and 23% for
the other radiologist.
 Permanent section of the renal biopsies was
considered non diagnostic in 20% of the 22
 Results of NSS with normal opposite
kidney
 17 studies with 909 patients
 Disease-specific survival 96.8% (90-100)
 Local recurrence 1.4% (0-7.3)
 Tumour size was 2-4.3cm
 Comparison of 5yr CSS in RN and PN
 Butler et al: RN 97% and PN 100%.
 Lerner et al : RN 96% and NSS 92%.
 Lau et al: Local tumor recurrence-free
survival was slightly higher in the NSS
cohort (5.4% v 0.8%; P .18)
23
 Distinct differences between kidney
donors and renal tumor patients exist.
 Donors tend to be carefully screened
for medical comorbidities, are generally
young and healthy
 Renal tumor patients are not screened,
are older (mean age 61 years) and
often have significant comorbidities
that can affect the kidney function
 As patients age, nephrons atrophy and
GFR progressively decreases
24
Harvard Medical School examined the
non tumor bearing kidney of patients
undergoing RN
110 nephrectomy specimens of which 39 were
less than 5 cm
Only 10% of patients had completely normal
adjacent renal tissue
28% were found to have vascular sclerotic
changes.
In the remaining 62% of cases diabetic
nephropathy, glomerular hypertrophy,
mesangial expansion and diffuse
glomerosclerosis, was noted 25
MSKCC investigators studied RF in their
partial and radical nephrectomies
161 PN and 857 RN
Renal insuffeciency was defined as sCr
above 2mg/dl
111 patients (10.9%), experienced renal
insufficiency at a median of 14.4 months
from operation.
105/111 (95%) underwent RN
On multivariate analysis, age, sex,
preoperative creatinine and percentage
change in kidney volume were all significant
factors associated with freedom from renal 26
 MSKCC compared PN & RN renal function
using GFR
 MDRD formula was used to estimate GFR in a
retrospective fashion
 GFR<60 ml/min/1.73m2 was considered a CKD
 662 patients with a normal serum creatinine
and two healthy kidneys that underwent
either elective PN or RN for a RCT 4cm or less.
 171 patients (26%) had preexisting CKD
(GFR<60) prior to operation despite two intact
kidneys and normal serum creatinine .

27
 3-year probability of freedom from new onset
of GFR<60 was 80% after PN, and only 35%
after RN.

 Multivariable analysis indicated that RN

remained an independent risk factor for the
development of new-onset CKD

 This important data makes RN for SRMs

unjustified and POTENTIALLY DANGEROUS to
the long-term health of the patient.

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.
28
Renal function & Nx (Most
recent article)
 86 RFA, 85 PN & 71 RN
 Preoperatively stage 3
CKD in 65/242 patients
(26.7%)
 3-year freedom from a
CKD
 95.2% RFA
 70.7% PN
 39.9% RN
 RN was an independent
risk factor for stage 3 CKD
 RN vs RFA HR 34.3, 95% CI
4.28–275
 RNSM,
Lucas vsStern
PNJM,HRAdibi10.9,
M, et al:95% CI Outcomes in Patients Treated for Renal Masses
Renal Function
Smaller Than 4 cm by Ablative and Extirpative Techniques. J UROL 179:75-80, 2008
1.36–88.7 29
Corman et al compared the morbidity
and mortality of patients undergoing
either RN or NSS
1,373 RN & 512 NSS
Rates of postoperative progressive renal failure,
acute renal failure, urinary tract infection,
prolonged ileus, transfusion, deep wound
infection, or length of hospitalization were
comparable.
The 30-day mortality rates were 2.0% and 1.6%
for patients undergoing RN and NSS,
respectively (P .58).
30
Shinohara et al

 15 RN and 51 NSS cases

 NSS had a significantly higher score on
physical function in a standardized quality-of-
life questionnaire than patients treated with
RN (P .05).
 NSS patients were also found to have less
postoperative fatigue, sleep disturbance, pain,
and constipation than patients who were
treated with RN.

Shinohara N, Harabayashi T, Sato S, et al: Impact of nephron-sparing surgery on quality of life in

patients with localized renal cell carcinoma.Eur Urol 39:114-119, 2001 31
 Shekarriz et al compared the costs of
RN and NSS in a retrospective study
 No significant differences were seen
in the length of hospital stay, or
complication rates between the RN
and NSS patients
 Cost of care was comparable

Shekarriz B, Upadhyay J, Shekarriz H, et al: Comparison of costs and complications of radical and
partial nephrectomy for treatment of localized renal cell carcinoma. Urology 59:211-215, 32
 Several improvements happened in
the field of PN
 Surgical margin
 Tumor size
 Tumor location
 Renal imaging
 Laparoscopic PN

33
Traditionally, 1 cm of normal
parenchyma is needed as a SM
In Centrally located tumors a 1 cm
SM may be techniqually difficult
Lerner et al compared the outcomes of NSS 185
patients with RN in 209 matched patients
NSS consisted of PN in 82 patients and
enucleation in 87 patients.
They found no difference in the rate of CSS or
PFS between patients treated by PN vs.
enucleation.

Lerner SE, Hawkins CA, Blute ML, et al: disease outcome in patients with low stage renal cell 34
 Sutherland et al examined the issue
of SM for NSS in 44 PN specimens.
 The mean and median sizes of negative
margins were 0.25 and 0.2 cm, respectively
(range, 0.05 to 0.7 cm)
 3 patients had positive SM
 One patient with positive SM developed
multiple local and systemic recurrences.
 None of the other patients had tumor
recurrence with a mean follow-up for this
series of 49 months.
 The authors concluded that only a minimal
margin of less than 5 mm is required when 35
Multiphasic CT with reconstruction Intra operative US

6.5mm (3D)

36
 Several studies now show that the
equivalent oncologic outcomes of PN
may extend to select 7 cm renal
masses
 Leibovich et al (Mayo clinic, 2004)
 NSS (n 91) vs RN (n 841) for tumors 4 to 7
5 yr NSS RN SIGNF.
cm.CSS 98% 86% NS
Recurrence-free 94% 98% NS
survival
metastasis-free 94% 83% NS
survival

 NSS for 4 to 7 cm RCC results in excellent

outcome in appropriately selected patients. 37
 19 central and 67 peripheral tumors.
 Ischemia time (55 vs 34 minutes, p <0.05)
 Entry of the collecting system (74% versus
47%, p <0.05)
 No impact on 5-year CSS (100% central v
97% peripheral )
 Comparable tumor recurrence rates (5.7% v
4.5%)
 Renal function (sCr 1.43 mg/dL in both
groups)
 NSS is technically more difficult in centrally
located lesions, leading to longer ischemia
times and increased incidence of collecting
38
system injuries
 LPN offers
 Shorter hospitalization, more rapid
convalescence.
 Decreased pain, and improved cosmesis.
 Comparable CSS and RF with OPN
(intermediate FU)

 LPN is associated with

 Techniqually difficult
 Longer warm renal ischemia time
 More major intraoperative complication
39
 According to SEER database, only
20% of all RCTs between 2 and 4cm
were treated by PN in 2001
 In England, in 2002, only 108 (4%)
PN out of 2671 nephrectomies were
performed .

 Widespread training in partial

nephrectomy and enhanced
utilization, whether by open or
laparoscopic approaches, is clearly
40
 RCC remains primarily a surgical
disease; however, the surgical
management of RCC continues to
evolve.

 For appropriately selected tumors,

NSS is equally effective for control of
cancer, diminishes the risk of renal
failure, and offers superior quality of
life with no significant differences in
complications or cost.
41