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Linfoadenectomia e nefrectomia citoriduttivaLinfoadenectomia e nefrectomia citoriduttiva
Vincenzo Ficarra
Direttore Clinica di Urologia
Azienda Ospedaliera Universitaria di Udine
" ... to occlude the renal artery at an early stage of " ... to occlude the renal artery at an early stage of
the procedure and remove the renal tumor en bloc the procedure and remove the renal tumor en bloc
with the lymphatics"with the lymphatics"
Radical nephrectomy for RCC: the Robson
criteria
"The para"The para--aortic (left) and paraaortic (left) and para--caval (right) lymph caval (right) lymph
nodes should be removed from the crus of the nodes should be removed from the crus of the
diaphragm distally to the biforcation of the aorta".diaphragm distally to the biforcation of the aorta".
Robson CJ J Urol 1963; 89: 37Robson CJ J Urol 1963; 89: 37--4242
Template for extended LND dissection
Crispen PL. et al. Eur Urol. 2011; 59: 18Crispen PL. et al. Eur Urol. 2011; 59: 18--230230
•• The available technology is capable of The available technology is capable of
accurately identifying only large lymph node accurately identifying only large lymph node
metastasesmetastases
Imaging techniques and nodal metastases
staging
metastasesmetastases
•• Patients with (micro)metastases in normalPatients with (micro)metastases in normal--
sized nodes who might benefit from LND sized nodes who might benefit from LND
cannot be visualized by any of the available cannot be visualized by any of the available
imaging techniques (US, CT, MRI)imaging techniques (US, CT, MRI)
Capitanio U. et al. Eur Urol. 2011; 60: 1212Capitanio U. et al. Eur Urol. 2011; 60: 1212--12201220
Nomogram predicting hilar LNI in RCC
Hutterer GC. et al. Int J Cancer 2007; 121: 2556Hutterer GC. et al. Int J Cancer 2007; 121: 2556--6161
(external validation) Accuracy: 78.4%
Role of extended LND in cN0 RCC:
EORTC trial 30881
772 cases
383 RN +
extended LND
1. Expected 5-year survival rate
85 %
Blom JHM et al. Eur Urol. 2009; 55: 28Blom JHM et al. Eur Urol. 2009; 55: 28--3434
772 cases
(T1-3, N0M0)389 RN
alone
1. Expected 5-year survival rate
70 %
Role of extended LND in cN0 RCC:
EORTC trial 30881
Blom JHM et al. Eur Urol. 2009; 55: 28Blom JHM et al. Eur Urol. 2009; 55: 28--3434
EORTC trial 30881: clinical characteristics
Blom JHM et al. Eur Urol. 2009; 55: 28Blom JHM et al. Eur Urol. 2009; 55: 28--3434
* TNM, 1978
*
EORTC trial 30881: Pathological
characteristics
Blom JHM et al. Eur Urol. 2009; 55: 28Blom JHM et al. Eur Urol. 2009; 55: 28--3434
* TNM, 1978
*
Role of extended LND in M0 RCC:
SEER database
Sun M. et al. Sun M. et al. BJU Int 2014; 113: 36BJU Int 2014; 113: 36––4242. .
Pathological LNI prevalence according to
pathological characteristics
Capitanio U. et al. Eur Urol. 2011; 60: 1212Capitanio U. et al. Eur Urol. 2011; 60: 1212--12201220
High-risk clear cell RCC for LNI
• pT3-4 tumors
• Grade 3-4
• Sarcomatoid dediff.
Crispen PL. et al. Eur Urol. 2011; 59: 18Crispen PL. et al. Eur Urol. 2011; 59: 18--2323
• Sarcomatoid dediff.
• Size >10 cm
• Coagulative necrosis
Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125
*
Accuracy 86.9%
Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125
*
The use of a threshold of 3% would allow
the avoiding of ~50% of the LNDs
Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125Capitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125
*
Rational algorithm for RCC patient candidates
for LND
Capitanio U. et al. Eur Urol. 2011; 60: 1212Capitanio U. et al. Eur Urol. 2011; 60: 1212--12201220
EORTC trial 30881: cT3-4 subanalysis
Blom JHM et al. Eur Urol. 2009; 55: 28Blom JHM et al. Eur Urol. 2009; 55: 28--3434
*
Lymph node dissection in locally
advanced Renal Cell Carcinoma
Bekema HJ et al. Eur Urol. 2013; 64: 799Bekema HJ et al. Eur Urol. 2013; 64: 799--810810
*
Lymph node dissection in locally
advanced Renal Cell Carcinoma
Bekema HJ et al. Eur Urol. 2013; 64: 799Bekema HJ et al. Eur Urol. 2013; 64: 799--810810
*
• There is insufficient evidence to draw any conclusions on
Bekema HJ et al. Eur Urol. 2013; 64: 799Bekema HJ et al. Eur Urol. 2013; 64: 799--810810
*
• There is insufficient evidence to draw any conclusions on
oncologic outcomes for patients having concomitant LND
compared with patients having RN alone for cT3–T4N0M0
RCC
• The quality of evidence is generally low and the
results potentially biased.
Rational algorithm for RCC patient candidates
for LND
Capitanio U. et al. Eur Urol. 2011; 60: 1212Capitanio U. et al. Eur Urol. 2011; 60: 1212--12201220
Role of extended LND in cN+M0 RCC
Pantuck AJ J Urol 2003; 169: 2076Pantuck AJ J Urol 2003; 169: 2076--8383
Role of LND in patients with distan metastases:
fractional percentage of tumour volume removed
Pierorazio PM et al BJU Inter 2007; 100: 755Pierorazio PM et al BJU Inter 2007; 100: 755--759759
Rational algorithm for RCC patient candidates
for LND
• cT2b (>10 cm); N0
• cT3-4; N0• cT3-4; N0
• cN+
• M+
Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)Russell CM et al. J Urol. 2014; (in press)
Isolated Nodal Recurrences
L R
Russell CM et al. J Urol. 2014; (in press)Russell CM et al. J Urol. 2014; (in press)
Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)Russell CM et al. J Urol. 2014; (in press)
• Surgical resection represents the best curative
option for patients who present with isolated
retroperitoneal lymph node recurrence of RCC
Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)Russell CM et al. J Urol. 2014; (in press)
• Durable postoperative progression-free survival
is attainable in many patients regardless of
histology or clinical TNM stage
Role of Nephrectomy in mRCC
• Curative (Nephrectomy + metastasectomy)
• Cytoreductive (To resect primary tumor in the
prior to the initiation of systemic therapy for
unresectable metastases)
• Palliative (To improve symptoms)
- pain related to the kidney mass
- intractable hematuria
- paraneoplastic syndrome
Palliative Nephrectomy in mRCC
492/5378 (9.1%) cases surgically treated from 1995-2007
SATURN database – LUNA fundation (unpublished data)
Combined analysis (SWOG/EORTC)
Flanigan RC et al J Urol 2004; 171: 1071Flanigan RC et al J Urol 2004; 171: 1071--10761076
13.6 months
7.8 months
+ 5.8 months
• Cytoreductive nephrectomy significantly improve
overall survival in patients with mRCC treated
with IFN-alpha independent of patients
Combined analysis (SWOG/EORTC)
- performance status
- site of metastasis (lung)
- presence of measurable disease
- (?) single Vs multiple metastases
Flanigan RC et al J Urol 2004; 171: 1071Flanigan RC et al J Urol 2004; 171: 1071--10761076
Population-based assessment
(SEER - 1988-2004)
Zini L. et al Urology 2009; 73: 342Zini L. et al Urology 2009; 73: 342--346346
Guidelines on Renal Cell Carcinoma
EAU, 2013 ESMO, 2010 NCCN, 2013
• Palliative or complementary
systemic treatments are
necessary
• Recommended for mRCC
patients with good PS when
combined with IFN-alfa
• Standard of cure in
patients receiving
cytokines [1, A]
• Role of CN needs to be
re-evaluated in the present
era of molecular targeted
• Curative intent in patients
with resectable solitary
metastasis
• Cytoreductive intent in
patients with good PS and
without brain metastasiscombined with IFN-alfa
(Grade A)
• Only limited data are
available addressing the
value of CN combined with
targeting agents
era of molecular targeted
therapies
without brain metastasis
• Role of CN and patients
selection may warrant
assessment in the setting of
targeted therapies
• Palliative in symptomatic
mRCC
A population-based study examining the
role of nephrectomy prior to treatment
Warren M. et al Can Urol Assoc J 2009; 3 (4): 281Warren M. et al Can Urol Assoc J 2009; 3 (4): 281--8989
Value of Cytoreductive Nephrectomy for mRCC
in the Era of Targeted Therapy
Choueiri TK. et al J Urol 2011; 185: 60Choueiri TK. et al J Urol 2011; 185: 60--6666
Value of Cytoreductive Nephrectomy for mRCC
in the Era of Targeted Therapy
CN: 20% sarcomatoid features
Non CN: 3% sarcomatoid feature
You D. et al J Urol 2011; 185: 54You D. et al J Urol 2011; 185: 54--5959
Sarcomatoid feature: HR 2.7 (1.2-6.7)
Ideal candidate for cytoreductive nephrectomy
• Lactate dehydrogenase
• Albumin level
• Symptoms (S3)
MD Anderson: 470 CN and 88 medical therapy only
• Symptoms (S3)
• Liver metastasis
• N+ retroperitoneal
• N+ supradiaphragmatic
• ≥ T3
Culp SH et al Cancer 2010; 116: 3378Culp SH et al Cancer 2010; 116: 3378--8888
Candidate for cytoreductive nephrectomy
• Good surgical risk (good performance status)
• Limited metastatic tumor burden to lung or bone
• Extensive metastatic disease with systemic • Extensive metastatic disease with systemic
therapy planned
• Symptoms related to the primary tumor
NCCN Guidelines, 2013NCCN Guidelines, 2013
Eligibility Criteria
• ECOG PS of 0 or 1
• Clear cell histology
• Resectable primary tumour
Cytoreductive Nephrectomy
+ Sunitinib
Random
ization
(N=576)
CARMENA (NCT00930033) TrialStudy start data: May 2009 – Estimated Study completition: May 2013
Hopitaux de Paris and Pfizer Hopitaux de Paris and Pfizer –– www.clinicaltrials.govwww.clinicaltrials.gov
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
• Resectable primary tumour
• No prior systemic treatment
• Adequate organ function Sunitinib alone
Random
ization
Eligibility Criteria
• Clear cell histology
• Resectable primary tumour
• Asymptomatic primary tumour
Sunitinib (3 course) +
Deferred CN
Random
ization
(N= 458)
SURTIME (EORTC 30073) TrialStudy start data: April 2010 – Estimated Study completition: October 2014
Hopitaux de Paris and Pfizer Hopitaux de Paris and Pfizer –– www.clinicaltrials.govwww.clinicaltrials.gov
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
• Asymptomatic primary tumour
• Measurable disease
• No prior systemic treatment
• Adequate organ function
Immediate CN +
Sunitinib (3 course)
Random
ization
Conclusions
• Nephrectomy is still an important part of
the multidisciplinary treatment of RCC
• Targeted agents represent a substantial
improvement but since they are not
curative, the cytoreductive paradigm iscurative, the cytoreductive paradigm is
still relevant
• Today, the more relevant question should
address the timing of and appropriate
patient selection for cytoreductive
nephrectomy