Dr Ho lectured at the Asian Oncology Summit 2013 in Bangkok on the surgical opinion on management of renal cell carcinoma. He presented to a varied audience of medical oncologist, radiation oncologist, urologists, researchers, para clinical staff and nurses. The most interesting aspect of the lecture was on the role of urologists in management of Stage 4 kidney cancer in the era of 'targeted therapy'. The role of cytoreductive nephrectomy was reviewed potential future developments in this area was discussed

1. Ho Siewhong
Urologist
Gleneagles & Mt Elizabeth Novena Hospitals
Singapore
SURGERY FOR RENAL CELL CARCINOMA

2. OUTLINE
Renal cell carcinoma
• Small renal mass
• Stage 1 & 2
• Stage 3 – vein involvement
• Stage 3 – lymphadenopathy
• Stage 4 – role cytoreductive nephrectomy

3. SMALL RENAL MASS
• < 4 cm lesions in kidney
• Increasing incidence with ‘routine’ abdominal imaging
• Renal cell carcinoma, angiomyolipoma, oncocytoma
• Treatment options of watchful wait, laparoscopic or open partial
neprhrectomy, enucleation, cyroablation, radio frequency
ablation
• Trending towards biopsy driven management algorithm

4. STAGING OF RENAL CELL CARCINOMA

5. STAGE 1 AND 2 (T1, T2) RENAL CELL CARCINOMA
• Surgery is the established
treatment
• Good results
Stage 5 Year Survival Rate
I 81%
II 74%
III 53%
IV 8%
2001 and 2002 by the National Cancer Data Base, American
Cancer Society

6. SURGICAL TRENDS IN STAGE 1 & 2 RENAL CELL
CARCINOMA
• Gradual movement from open surgery to laparoscopic radical nephrectomy in
last 15 years
• Laparoscopic radical nephrectomy can be performed for tumors up to 10 cm in most centers
•
• Followup was 11.2 years. Mean tumor size was 5 cm. Pathological stage was pT1a in 41% of
cases, pT1b in 30%, pT2 in 15%, pT3a in 10%, pT3b in 3% and pT4 in 1%. High grade tumors
(Fuhrman 3 or greater) were present in 18 cases (28%). A positive surgical margin occurred in 1
case. Actual 10-year overall, cancer specific and recurrence-free survival rates were 65%, 92%
and 86%, respectively.
Gill et al, Journal of Urology. 182(5):2172-6, 2009 Nov
• Followup was 73 months for the laparoscopic group and 80 months for the open group. Of the
67 patients who underwent laparoscopic surgery, 53 survived without any recurrence of
disease,. Laparoscopic port site metastasis did not develop in any patients. A comparison of the
5 and 10-year disease-free survival rates of the laparoscopic and open groups revealed no
significant differences. In addition, the 5 and 10-year cancer specific and actuarial survival rates
were not significantly different.
Kavoussi et al, J Urol. 2005 Oct;174(4 Pt 1):1222-5

7. LAPAROSCOPIC RADICAL NEPRHECTOMY
• No RCT between open and
laparoscopic radical nephrectomy
• Comparable oncology outcome as
open radical nephrectomy
• Less analgesia requirement post
surgery, quicker return to work
Hemal et al. J Urol. 2007
Mar;177(3):862-6
• Similar surgery time, blood loss,
transfusion rate

8. LAPAROSCOPIC RADICAL NEPHRECTOMY
• The standard of care for patients with T2
tumours and those renal masses not
treatable by nephron-sparing surgery
• Should not be performed in patients with
T1 tumours for whom partial nephrectomy
is indicated
EUA Guidelines 2013 Update

9. SURGICAL TRENDS IN STAGE 1 & 2 RENAL CELL
CARCINOMA – NEPHRON SPARING SURGERY
• Nephron sparing surgery for small tumors, T1a (<4 cm)
• Open partial nephrectomy
• Laparoscopic partial nephrectomy – technically demanding surgery
• 541 patients with small (<=5 cm), solitary, T1-T2 N0 M0 (Union Internationale Contre le
Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) were randomised
to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-
Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904. Median follow-up was 9.3
yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and
75.7% for NSS. The test for noninferiority is not significant (p=0.77), and test for
superiority is significant (p=0.03). In RCC patients and clinically and pathologically eligible
patients, the difference is less pronounced (HR=1.43 and HR=1.34, respectively), and the
superiority test is no longer significant (p=0.07 and p=0.17, respectively). The study was
prematurely closed due to poor accrual
Van Poppel et al, European Urology. 59(4):543-52, 2011 Apr.

10. PARTIAL NEPHRECTOMY
• Challenges of partial nephrectomy – margins and clamp time
• Laparoscopic and open partial nephrectomy: a matched-pair comparison of 200 patients.
LPN provides similar results compared to open surgery. Positive Surgical Margin rates
were comparable after LPN and OPN
Marszalek et al. Eur Urol. 2009 May;55(5):1171-8
• Retrospective analysis of 982 patients who underwent standard partial nephrectomy and
537 who had simple enucleation. Median follow up 51 and 54.4 months. 5 and 10 year
progression free survival 88.9% and 82% for partial nephrectomy, and 91.4% and 90.8%
after enucleation (p=0.09). 5 and 10 year cancer specific survival 93.9% and 91.6% for
partial nephrectomy, and 94.3% and 93.2% after enucleation (p=0.94)
Minervini et al, Journal of Urol. 185(5): 1604-10, 2011 May

11. PARTIAL NEPHRECTOMY
Hilar clamping
decreases blood
loss, better
visual field
Intra operative
ultrasound
guided
resection

12. SURGICAL TRENDS IN STAGE 1 & 2 RENAL CELL
CARCINOMA
• Percutaneous / laparoscopic cryoablation or radio frequency ablation
• Observational single-institution cohort study, involving consecutive patients
with a solitary histologically confirmed T1a RCC treated by RFA or PN and
followed for a minimum of 5 yr. 37 patients in each. The RFA cohort was
significantly older and had more advanced comorbidities. Median follow-up
was 6.5 yr. The 5-yr OS was 97.2% versus 100% (p = 0.31), CSS was 97.2%
versus 100% (p = 0.31
Olweny et al. Eur Urol. 61(6):1156-61, 2012 Jun
• Percutaneous biopsy confirmation is essential
• Older patient, impaired renal function, solitary kidney, multiple sites can be
treated

13. T3 RENAL CELL CARCINOMA – RENAL VEIN, IVC
THROMBUS
Thrombus

14. T3 RENAL CELL CARCINOMA – RENAL VEIN, IVC
THROMBUS
• Better survival results than LN involvement
• 35 patients underwent IVC thrombectomy with radical nephrectomy between January
1997 and December 2006. The limit of tumor extension was level I in 10 patients (28.6%),
level II in 17 (48.6%), and level III and IV in 4 patients each (11.4%). Liver mobilization
with hepatic vascular exclusion was performed in 12 patients and cardiopulmonary
bypass in 7. There was no operative mortality, and the overall survival at 5-yr was 50.8%.
Ahn et al, J Korean Med Sci. 2010 January; 25(1): 104–109.

15. T3 RENAL CELL CARCINOMA – NODE +VE
• Presence of pre-operative regional lymphadenopathy indicates poorer prognosis
Median survival of 14.7 mths v/s 8.5 mths (Vasselli et al. J Urol 2001)
20.4 mths v/s 10.5 mths (Pantuck et al. J Urol 2003)
• Role of lymph node dissection
• Routine regional LN dissection in pre-operative undetectable LN does not offer improvement in
overall survival, time to progression of disease, or progression-free survival. EORTC
Genitourinary Group, randomized phase 3 trial comparing radical nephrectomy with a complete
lymphadenectomy to radical nephrectomy alone
Blom et al. Eur Urol. 2009; 55(1):28-34
• Extended lymphadenectomy is not recommended since it does not appear to improve survival.
Restricted to staging purposes with dissection of palpable and/or enlarged lymph nodes
EAU Guidelines, 2013
• Regional LN dissection in pre-operative lymphadenopathy should be considered to render the
patient radiographically disease free
- resectable with acceptable morbidity
- candidates for adjuvant trials

16. STAGE IV RENAL CELL CARCINOMA
• 1/3 incidentally detected renal cell carcinoma – metastatic / locally advanced
at presentation
• SWOG, EORTC trials – benefits of cytoreductive surgery (improvement in
overall survival by 6 mths)
Flanigan et al. J Urol 2004; 171(3)
• Radical nephrectomy (laparoscopic or open), resection of affected adjacent
organs, lymphadenectomy if lymphadenopathy is present
• Cytoreductive nephrectomy – not to be used indiscriminately, in most cases
cannot achieve cure
- part of a multimodality management

17. CYTOREDUCTIVE NEPHRECTOMY
• Palliates local symptoms
• Acceptable morbidity in selected patients
• Primary tumor may not respond to systemic therapy
• Improves patient outcomes (earlier studies)

18. HOW DOES CYTOREDUCTIVE NEPHRECTOMY
WORK?
• Effect of debulking of the tumor mass
• Concept of Fractional percentage tumor volume (FPTV)
Barbastefano et al. BJU int (2010), Pierorazio et al. BJU Int (2007)
• Interrupts negative influence of tumor micro enviroment
Changes Effect on host
Secretion of VEGF, PDGF, FGF and TGF-β1
by tumor cells
Angiogenesis and cell proliferation
Expression of costimulatory molecules CTLA-4
and the B7 family on tumor cell surface
Downregulation of effective immune response
Migration of Tregs, MDSCs and TAMs into the
tumor environment
Downregulation of T-cell-mediated anti-tumor
response

19. CYTOREDUCTIVE NEPHRECTOMY IN THE ERA
OF TARGETED THERAPY
• Tyrosine kinase inhibitors, VEFT antibodies, mTOR inhibitors
• No results from RCT that cytoreductive nephrectomy is beneficial in era of targeted
therapy
• Competition from ‘better’ systemic therapy
• Morbidity of Cytoreductive nephrectomy may delay administration of ‘effective’ systemic
therapy
• Role of presurgical targeted therapy to help identify patients that may or may not benefit
from surgery

20. LAPAROSCOPIC CYTOREDUCTIVE
NEPHRECTOMY

21. CYTOREDUCTIVE NEPHRECTOMY IN THE ERA
OF TARGETED THERAPY
Biopsy proven
Clear Cell RCC,
completion 2016

22. PROPOSED ALGORITHM FOR TIMING OF
CYTOREDUCTIVE NEPHRECTOMY

23. Christopher Wood, MD Anderson Cancer Center

24. No role for
adjuvant therapy,
EUA Guidelines
for T3 LN +ve
Decision

25. CONCLUSIONS
• Surgery with potential for cure for stage 1 and 2 disease
• Move towards laparoscopic radical nephrectomy and
laparoscopic partial nephrectomy in smaller tumors
• No role for routine lymph node dissection
• Multi surgical approach for IVC thrombectomy – liver and
cardiothoracic surgeon
• Evolving role of cytoreductive nephrectomy for metastatic
disease in the era of target chemotherapy

26. THANK YOU