1. Linfoadenectomia e nefrectomia citoriduttiva
Vincenzo Ficarra
Direttore Clinica di Urologia
Azienda Ospedaliera Universitaria di Udine

2. 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

3. Lymphatic drainage of the Kidney and extended LND dissection

4. Template for extended LND dissection
Crispen PL. et al. Eur Urol. 2011; 59: 18-23

5. Imaging techniques and nodal metastases staging
The available technology is capable of accurately identifying only large lymph node metastases
Patients with (micro)metastases in normal-sized 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:

6. Nomogram predicting hilar LNI in RCC
(external validation) Accuracy: 78.4%
Hutterer GC. et al. Int J Cancer 2007; 121:

7. Role of extended LND in cN0 RCC: EORTC trial 30881
383 RN +
extended LND
85 %
772 cases
(T1-3, N0M0)
1. Expected 5-year survival rate
389 RN
alone
70 %
Blom JHM et al. Eur Urol. 2009; 55: 28-34

8. Role of extended LND in cN0 RCC: EORTC trial 30881
Blom JHM et al. Eur Urol. 2009; 55: 28-34

9. EORTC trial 30881: clinical characteristics*
* TNM, 1978
Blom JHM et al. Eur Urol. 2009; 55: 28-34

10. EORTC trial 30881: Pathological characteristics*
* TNM, 1978
Blom JHM et al. Eur Urol. 2009; 55: 28-34

12. Role of extended LND in M0 RCC: SEER database
Sun M. et al. BJU Int 2014; 113: 36–42.

13. Pathological LNI prevalence according to pathological characteristics
Capitanio U. et al. Eur Urol. 2011; 60:

14. 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

15. *
Capitanio U. et al. BJU Inter. 2014; doi: /bju.12125

16. Accuracy 86.9% *
Capitanio U. et al. BJU Inter. 2014; doi: /bju.12125

17. The use of a threshold of 3% would allow the avoiding of ~50% of the LNDs*
Capitanio U. et al. BJU Inter. 2014; doi: /bju.12125

18. Rational algorithm for RCC patient candidates for LND
Capitanio U. et al. Eur Urol. 2011; 60:

19. *
Bekema HJ et al. Eur Urol. 2013; 64:

20. *
Bekema HJ et al. Eur Urol. 2013; 64:

21. EORTC trial 30881: cT3-4 subanalysis*
Blom JHM et al. Eur Urol. 2009; 55: 28-34

22. Lymph node dissection in locally advanced Renal Cell Carcinoma*
Bekema HJ et al. Eur Urol. 2013; 64:

23. Lymph node dissection in locally advanced Renal Cell Carcinoma*
Bekema HJ et al. Eur Urol. 2013; 64:

24. * 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:

25. Rational algorithm for RCC patient candidates for LND
Capitanio U. et al. Eur Urol. 2011; 60:

26. Role of extended LND in cN+ RCC

27. Role of extended LND in cN+M0 RCC
Pantuck AJ J Urol 2003; 169:

28. Role of LND in patients with distan metastases: fractional percentage of tumour volume removed
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Pierorazio PM et al BJU Inter 2007; 100:

29. Rational algorithm for RCC patient candidates for LND
cT2b (>10 cm); N0
cT3-4; N0
cN+ M+

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

33. Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)

34. Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)

35. Isolated Nodal Recurrences
Russell CM et al. J Urol. 2014; (in press)

36. 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)

37. 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

38. Palliative Nephrectomy in mRCC
492/5378 (9.1%) cases surgically treated from
SATURN database – LUNA fundation (unpublished data)

39. Combined analysis (SWOG/EORTC)
13.6 months
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
+ 5.8 months
7.8 months
Flanigan RC et al J Urol 2004; 171:

40. 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
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Flanigan RC et al J Urol 2004; 171:

41. Population-based assessment (SEER - 1988-2004)
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Zini L. et al Urology 2009; 73:

42. 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 (Grade A)
Only limited data are available addressing the value of CN combined with targeting agents
Standard of cure in patients receiving cytokines [1, A]
Role of CN needs to be re-evaluated in the present era of molecular targeted therapies
Curative intent in patients with resectable solitary metastasis
Cytoreductive intent in 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
Gli obiettivi del nostro studio sono di… 42

43. Cytoreductive Nephrectomy in the era of Targeted molecular agents
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.

44. A population-based study examining the role of nephrectomy prior to treatment
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Warren M. et al Can Urol Assoc J 2009; 3 (4):

45. Value of Cytoreductive Nephrectomy for mRCC in the Era of Targeted Therapy
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Choueiri TK. et al J Urol 2011; 185: 60-66

46. 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 ( )
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
You D. et al J Urol 2011; 185: 54-59

47. 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
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
Culp SH et al Cancer 2010; 116:

48. 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
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.
NCCN Guidelines, 2013

49. CARMENA (NCT ) Trial
Study start data: May 2009 – Estimated Study completition: May 2013
Eligibility Criteria
ECOG PS of 0 or 1
Clear cell histology
Resectable primary tumour
No prior systemic treatment
Adequate organ function
Cytoreductive Nephrectomy
+ Sunitinib
(N=576)
Randomization
Sunitinib alone
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
Hopitaux de Paris and Pfizer –

50. SURTIME (EORTC 30073) Trial
Study start data: April 2010 – Estimated Study completition: October 2014
Eligibility Criteria
Clear cell histology
Resectable primary tumour
Asymptomatic primary tumour
Measurable disease
No prior systemic treatment
Adequate organ function
Sunitinib (3 course) +
Deferred CN
(N= 458)
Randomization
Immediate CN +
Sunitinib (3 course)
Primary endpoint: Overall Survival
Secondary endpoints: Objective response, PFS, Safety
Hopitaux de Paris and Pfizer –

51. 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
However, not only an ideal cancer staging system should aid the clinician in the appropriate selection of therapeutic options but above all, in my opinion, it should stratify the patient’s risk of cancer progression or cancer death.