Linfoadenectomia e nefrectomia citoriduttiva - overgroup.eu · Linfoadenectomia e nefrectomia citoriduttiva Vincenzo Ficarra Direttore Clinica di Urologia Azienda Ospedaliera Universitaria

Linfoadenectomia e Linfoadenectomia e

nefrectomia citoriduttivaVincenzo FicarraDirettore Clinica di Urologia

Azienda Ospedaliera Universitaria di Udine

" ... to occlude the " ... to occlude the renalrenal arteryartery atat an an earlyearly stage of stage of

the procedure and the procedure and removeremove the the renalrenal tumortumor en en blocbloc

with the with the lymphaticslymphatics""

Radical nephrectomy for RCC: the

Robson criteria

"The para"The para--aorticaortic ((leftleft) and para) and para--caval (right) caval (right) lymphlymph

nodesnodes shouldshould be be removedremoved from the from the cruscrus of the of the

diaphragmdiaphragm distallydistally to the to the biforcationbiforcation of the aorta".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

CrispenCrispen PL. et al. PL. et al. EurEur UrolUrol. 2011; 59: 18. 2011; 59: 18--2323

•• The The availableavailable technologytechnology isis capablecapable of of

accuratelyaccurately identifyingidentifying onlyonly large large lymphlymph nodenode

metastasesmetastases

Imaging techniques and nodal

metastases staging

metastasesmetastases

•• PatientsPatients with (micro)with (micro)metastasesmetastases in in normalnormal--

sizedsized nodesnodes whowho mightmight benefit from LND benefit from LND

cannotcannot be be visualizedvisualized by by anyany of the of the availableavailable

imagingimaging techniquestechniques (US, CT, MRI)(US, CT, MRI)

CapitanioCapitanio U. et al. U. et al. EurEur UrolUrol. 2011; 60: 1212. 2011; 60: 1212--12201220

Nomogram predicting hilar LNI in RCC

HuttererHutterer GC. et al. GC. et al. IntInt J J CancerCancer 2007; 121: 25562007; 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 %

BlomBlom JHM et al. JHM et al. EurEur UrolUrol. 2009; 55: 28. 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

SunSun M. et al. 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.

CrispenCrispen PL. et al. PL. et al. EurEur UrolUrol. 2011; 59: 18. 2011; 59: 18--2323

• Sarcomatoid dediff.

• Size >10 cm

• Coagulative necrosis

CapitanioCapitanio U. et al. BJU Inter. 2014; doi:10.1111/bju.12125U. 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


BekemaBekema HJ et al. HJ et al. EurEur UrolUrol. 2013; 64: 799. 2013; 64: 799--810810

*


*

EORTC trial 30881: cT3-4 subanalysis


*

Lymph node dissection in locally advanced

Renal Cell Carcinoma


*

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.


candidates 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

PierorazioPierorazio PM et al BJU Inter 2007; 100: 755PM et al BJU Inter 2007; 100: 755--759759


candidates for LND

• cT2b (>10 cm); N0

• cT3-4; N0• cT3-4; N0

• cN+

• M+

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

• Standard of cure in

patients receiving

cytokines [1, A]

• Role of CN needs to

be re-evaluated in the

• Curative intent in

patients with resectable

solitary metastasis

• Cytoreductive intent in

patients with good PS mRCC patients with good

PS when combined with

IFN-alfa (Grade A)

• Only limited data are

available addressing the

value of CN combined

with targeting agents

be re-evaluated in the

present era of molecular

targeted therapies

patients with good PS

and 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 Warren M. et al Can UrolUrol AssocAssoc J 2009; 3 (4): 281J 2009; 3 (4): 281--8989

Value of Cytoreductive Nephrectomy for

mRCC in the Era of Targeted Therapy

ChoueiriChoueiri TK. et al J TK. et al J UrolUrol 2011; 185: 602011; 185: 60--6666

Value of Cytoreductive Nephrectomy for

mRCC in the Era of Targeted Therapy

CN: 20% sarcomatoid features

Non CN: 3% sarcomatoid feature

YouYou D. et al J D. et al J UrolUrol 2011; 185: 542011; 185: 54--5959

Sarcomatoid feature: HR 2.7 (1.2-6.7)

Ideal candidate for cytoreductive

nephrectomy

• Lactate dehydrogenase

• Albumin level

MD Anderson: 470 CN and 88 medical therapy only

• Albumin level

• Symptoms (S3)

• Liver metastasis

• N+ retroperitoneal

• N+ supradiaphragmatic

• ≥ T3

CulpCulp SH et al SH et al CancerCancer 2010; 116: 33782010; 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

therapy planned

• Symptoms related to the primary tumor

NCCN NCCN GuidelinesGuidelines, 2013, 2013

Eligibility Criteria

• ECOG PS of 0 or 1

• Clear cell histology

• Resectable primary tumour

Cytoreductive Nephrectomy

+ Sunitinib

Ra

nd

om

iza

tio

n

(N=576)

CARMENA (NCT00930033) Trial

Study start data: May 2009 – Estimated Study completition: May 2013

HopitauxHopitaux de Paris and Pfizer 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 functionSunitinib alone

Ra

nd

om

iza

tio

n

Eligibility Criteria

• Clear cell histology


• Asymptomatic primary tumour

Sunitinib (3 course) +

Deferred CN

Ra

nd

om

iza

tio

n

(N= 458)

SURTIME (EORTC 30073) Trial

Study start data: April 2010 – Estimated Study completition: October 2014

HopitauxHopitaux de Paris and Pfizer 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)

Ra

nd

om

iza

tio

n

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

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Linfoadenectomia e nefrectomia citoriduttiva - overgroup.eu · Linfoadenectomia e nefrectomia citoriduttiva Vincenzo Ficarra Direttore Clinica di Urologia Azienda Ospedaliera Universitaria