vincenzo ficarra direttore clinica di urologia azienda ... · linfoadenectomia e nefrectomia...

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

Lymphatic drainage of the Kidney and extended

LND dissection

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


EORTC trial 30881: clinical characteristics


* TNM, 1978

*

EORTC trial 30881: Pathological

characteristics


* 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


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%


*

The use of a threshold of 3% would allow

the avoiding of ~50% of the LNDs


*

Rational algorithm for RCC patient candidates

for LND


Bekema HJ et al. Eur Urol. 2013; 64: 799Bekema HJ et al. Eur Urol. 2013; 64: 799--810810

*

EORTC trial 30881: cT3-4 subanalysis


*

Lymph node dissection in locally

advanced Renal Cell Carcinoma


*

• There is insufficient evidence to draw any conclusions on


*

• 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.


for LND


Role of extended LND in cN+ RCC

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


for LND

• cT2b (>10 cm); N0

• cT3-4; N0• cT3-4; N0

• cN+

• M+

Russell CM et al. J Urol. 2014; (in press)Russell CM et al. J Urol. 2014; (in press)

Isolated Nodal Recurrences



L R


• 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

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

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): 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


• No prior systemic treatment

• Adequate organ function Sunitinib alone

Random

ization

Eligibility Criteria

• Clear cell histology


• 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

vincenzo ficarra direttore clinica di urologia azienda ... · linfoadenectomia e nefrectomia...

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