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Linfoadenectomia e
nefrectomia citoriduttiva
Vincenzo Ficarra
Direttore Clinica di Urologia
Azienda Ospedaliera Universitaria di Udine
Radical nephrectomy for RCC: the
Robson criteria
" ... to occlude the renal artery at an early stage of
the procedure and remove the renal tumor en bloc
with the lymphatics"
"The para-aortic (left) and para-caval (right) lymph
nodes should be removed from the crus of the
diaphragm distally to the biforcation of the aorta".
Robson CJ J Urol 1963; 89: 37-42
Lymphatic drainage of the Kidney and
extended LND dissection
Template for extended LND dissection
Crispen PL. et al. Eur Urol. 2011; 59: 18-23
Imaging techniques and nodal
metastases staging
• The available technology is capable of
accurately identifying only large lymph node
metastases
• Patients with (micro)metastases in normalsized nodes who might benefit from LND
cannot be visualized by any of the available
imaging techniques (US, CT, MRI)
Capitanio U. et al. Eur Urol. 2011; 60: 1212-1220
Nomogram predicting hilar LNI in RCC
(external validation) Accuracy: 78.4%
Hutterer GC. et al. Int J Cancer 2007; 121: 2556-61
Role of extended LND in cN0 RCC:
EORTC trial 30881
383 RN +
extended LND
772 cases
(T1-3, N0M0)
85 %
1. Expected 5-year survival rate
389 RN
alone
Blom JHM et al. Eur Urol. 2009; 55: 28-34
70 %
Role of extended LND in cN0 RCC:
EORTC trial 30881
Blom JHM et al. Eur Urol. 2009; 55: 28-34
EORTC trial 30881: clinical characteristics
*
* TNM, 1978
Blom JHM et al. Eur Urol. 2009; 55: 28-34
EORTC trial 30881: Pathological
characteristics
*
* TNM, 1978
Blom JHM et al. Eur Urol. 2009; 55: 28-34
Role of extended LND in M0 RCC:
SEER database
Sun M. et al. BJU Int 2014; 113: 36–42.
Pathological LNI prevalence according to
pathological characteristics
Capitanio U. et al. Eur Urol. 2011; 60: 1212-1220
High-risk clear cell RCC for LNI
•
•
•
•
•
pT3-4 tumors
Grade 3-4
Sarcomatoid dediff.
Size >10 cm
Coagulative necrosis
Crispen PL. et al. Eur Urol. 2011; 59: 18-23
*
Capitanio 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.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.12125
Rational algorithm for RCC patient
candidates for LND
Capitanio U. et al. Eur Urol. 2011; 60: 1212-1220
*
Bekema HJ et al. Eur Urol. 2013; 64: 799-810
*
Bekema HJ et al. Eur Urol. 2013; 64: 799-810
EORTC trial 30881: cT3-4 subanalysis
*
Blom JHM et al. Eur Urol. 2009; 55: 28-34
Lymph node dissection in locally advanced
Renal Cell Carcinoma
*
Bekema HJ et al. Eur Urol. 2013; 64: 799-810
Lymph node dissection in locally advanced
Renal Cell Carcinoma
*
Bekema HJ et al. Eur Urol. 2013; 64: 799-810
•
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.
Bekema HJ et al. Eur Urol. 2013; 64: 799-810
Rational algorithm for RCC patient
candidates for LND
Capitanio U. et al. Eur Urol. 2011; 60: 1212-1220
Role of extended LND in cN+ RCC
Role of extended LND in cN+M0 RCC
Pantuck AJ J Urol 2003; 169: 2076-83
Role of LND in patients with distan metastases:
fractional percentage of tumour volume removed
Pierorazio PM et al BJU Inter 2007; 100: 755-759
Rational algorithm for RCC patient
candidates for LND
• cT2b (>10 cm); N0
• cT3-4; N0
• cN+
• M+
Russell CM et al. J Urol. 2014; (in press)
Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)
Isolated Nodal Recurrences
L
Russell CM et al. J Urol. 2014; (in press)
R
Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)
Isolated Nodal Recurrences
• Surgical resection represents the best curative
option for patients who present with isolated
retroperitoneal lymph node recurrence of RCC
• Durable postoperative progression-free survival
is attainable in many patients regardless of
histology or clinical TNM stage
Russell CM et al. J Urol. 2014; (in press)
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)
13.6 months
+ 5.8 months
7.8 months
Flanigan RC et al J Urol 2004; 171: 1071-1076
Combined analysis (SWOG/EORTC)
• Cytoreductive nephrectomy significantly improve
overall survival in patients with mRCC treated
with IFN-alpha independent of patients
- performance status
- site of metastasis (lung)
- presence of measurable disease
- (?) single Vs multiple metastases
Flanigan RC et al J Urol 2004; 171: 1071-1076
Population-based assessment
(SEER - 1988-2004)
Zini L. et al Urology 2009; 73: 342-346
Guidelines on Renal Cell Carcinoma
EAU, 2013
ESMO, 2010
NCCN, 2013
• Palliative or
complementary systemic
treatments are necessary
• Standard of cure in
patients receiving
cytokines [1, A]
• Curative intent in
patients with resectable
solitary metastasis
• Recommended for
mRCC patients with good
PS when combined with
IFN-alfa (Grade A)
• Role of CN needs to
be re-evaluated in the
present era of molecular
targeted therapies
• Cytoreductive intent in
patients with good PS
and without brain
metastasis
• Only limited data are
available addressing the
value of CN combined
with targeting agents
• Role of CN and patients
selection may warrant
assessment in the setting
of targeted therapies
• Palliative in
symptomatic mRCC
Cytoreductive Nephrectomy in the era of
Targeted molecular agents
A population-based study examining the
role of nephrectomy prior to treatment
Warren M. et al Can Urol Assoc J 2009; 3 (4): 281-89
Value of Cytoreductive Nephrectomy for
mRCC in the Era of Targeted Therapy
Choueiri TK. et al J Urol 2011; 185: 60-66
Value of Cytoreductive Nephrectomy for
mRCC in the Era of Targeted Therapy
CN: 20% sarcomatoid features
Non CN: 3% sarcomatoid feature
Sarcomatoid feature: HR 2.7 (1.2-6.7)
You D. et al J Urol 2011; 185: 54-59
Ideal candidate for cytoreductive
nephrectomy
MD Anderson: 470 CN and 88 medical therapy only
• Lactate dehydrogenase
• Albumin level
• Symptoms (S3)
• Liver metastasis
• N+ retroperitoneal
• N+ supradiaphragmatic
• ≥ T3
Culp SH et al Cancer 2010; 116: 3378-88
Candidate for cytoreductive nephrectomy
• Good surgical risk (good performance status)
• Limited metastatic tumor burden to lung or bone
• Extensive metastatic disease with systemic
therapy planned
• Symptoms related to the primary tumor
NCCN Guidelines, 2013
CARMENA (NCT00930033) Trial
Study start data: May 2009 – Estimated Study completition: May 2013
• ECOG PS of 0 or 1
• Clear cell histology
(N=576)
• Resectable primary tumour
• No prior systemic treatment
Randomization
Eligibility Criteria
Cytoreductive Nephrectomy
+ Sunitinib
• Adequate organ function
Sunitinib alone
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
Hopitaux de Paris and Pfizer – www.clinicaltrials.gov
SURTIME (EORTC 30073) Trial
Study start data: April 2010 – Estimated Study completition: October 2014
• Clear cell histology
• Resectable primary tumour
• Asymptomatic primary tumour
• Measurable disease
• No prior systemic treatment
(N= 458)
Randomization
Eligibility Criteria
Sunitinib (3 course) +
Deferred CN
• Adequate organ function
Immediate CN +
Sunitinib (3 course)
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
Hopitaux de Paris and Pfizer – www.clinicaltrials.gov
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 is
still relevant
• Today, the more relevant question should
address the timing of and appropriate
patient selection for cytoreductive
nephrectomy