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Surgery in Metastatic RCC
Lee Lui ShiongSenior Consultant and Head of Service, Sengkang General Hospital
Senior Consultant, Department of Urology, Singapore General Hospital
Visiting Consultant, National Cancer Centre
Clinical Senior Lecturer Yong Loo Lin School of Medicine
Adjunct Asst Professor, Dukes-GMS School of Medicine
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Disclosures
• Advisory board
– Janssen
– Bayer
– MSD
– BMS
• Clinical trial funding
– Janssen
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Fig. 1. Duration of survival in combined SWOG and EORTC trials. O, observation. N, nephrectomy
13.8 vs 7.6 months
7% CR
ROBERT C. FLANIGAN, G. MICKISCH, RICHARD SYLVESTER, CATHY TANGEN, H. VAN POPPEL, E. DAVID CRAWFORD
Cytoreductive Nephrectomy in Patients With Metastatic Renal Cancer: A Combined Analysis
The Journal of Urology, Volume 171, Issue 3, 2004, 1071–1076
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• Phase III
• CN+Sutent vs Sutent alone
• sunitinib - 50 mg daily , 28 on /14 off every 6 weeks
• primary end point overall survival
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Planned n=576
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• Did not recruit to size
• Weighted towards poor risk patients
• Median OS
– 18 month Sutent
– 13 months CN + Sutent
• Cytoreductive in these patients not likely to be
beneficial
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Why does CN work?
• Primary tumor ( immunologic ‘sink’)
• Reducing systemic burden of disease
• Reducing production of angiogenic factors
• J. Urol. 144; 1990: 614–617
• J. Urol. 147; 1992: 24–30
• Int. J. Urol. 2001; 275–281
• Am. J. Pathol. 158,2001: 735–743
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Utilisation of CN
Tsao, C et al. World J Urol (2013) 31: 1535
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Poor risk have limited incremental OS benefit
with CN
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No CN CN
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• Good prognosis – zero
• Intermediate – 1- 2
• Poor - ≥3
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Median OS 43.2 mths (95%CI 31.4-50.1)
Median OS 22.5 mths (95%CI 18.7- 25.1)
Median OS 7.8 mths (95%CI 6.5- 9.7)
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Lee LS et al. 2012 Nat. Rev. Urol. Predictive models for the practical management of renal cell
carcinoma
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Association of percentage of tumour burden removed with debulking nephrectomy and progression‐‐‐‐free survival in patients with metastatic renal cell carcinoma treated with
vascular endothelial growth factor‐‐‐‐targeted therapy
BJU International
Volume 106, Issue 9, pages 1266-1269, 23 MAR 2010 DOI: 10.1111/j.1464-410X.2010.09323.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2010.09323.x/full#f1
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Outcome after cytoreductive nephrectomy for metastatic renal cell carcinoma is predicted by fractional percentage of tumour volume removed
BJU International
Volume 100, Issue 4, pages 755-759, 15 AUG 2007 DOI: 10.1111/j.1464-410X.2007.07108.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2007.07108.x/full#f1
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Immediate versus deferred nephrectomy
Recruitment closed
Sunitinib
Primary outcome PFS
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Computed tomography scans showing partial response in primary tumor of metastatic renal cell carcinoma in patient treated with nivolumab; 48-year-old patient with low-volume but
poorly differentiated disease who developed progressive disease after sunitinib...
David F. McDermott et al. JCO 2015;33:2013-2020
©2015 by American Society of Clinical Oncology
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Metastatectomy
J Urol
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• Majority are pre-TKI era
• Selected cohort
• Solitary lung mets benefit most
• >1 mets site – some benefit but selection of patient not clear from this series
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Making Cytoreductive surgery safer
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Predicting surgical outcomes
• n=294, complication 12%, Clavien 5%
– Liver mets, intra-op transfusion, pN1
• n=195, 8% Clavien 3 complications
– age, Karnofsky status <80%
• n=279 patients, complication rate 22.6% Clavien 3 rate 8%.
– age,tumor size >10 cm, WHO performance status >2
• Eur Urol 2015;69:84-91
• BJU Int 2012;110:1276–82
• BJU lnt 2015; 116: 905-910
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• N=25
• Sunitinib n=12, others n=13
• 84% stable thombi level
• 4% (n=1) increase
• 12 % (n=3) decrease, median 1.5 cm
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Figure 1. OS following upfront surgery (M1 cohort)Clavien III and above (12%)
MVA -Atrial thrombus predictive of surgical complications
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Reducing surgical morbidity
• Patient selection is the key!!!
• Minimally invasive techniques if possible
• Optimise the patient
• No “occasional go” surgeon
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Alternatives to surgery
• Embolisation
• Radiation therapy
• Analgesia
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Selecting patients in 2018
• Cytoreductive surgery candidate
• IMDC criteria / MSKCC– Validated using population data
• Good to intermediate risk patients– OS >12 months
– symptomatic tumour
– Bulk of burden in kidney
– Limited metastatic sites (bone / brain mets)
• Part of multimodality therapy – minimising surgical morbidity
• Metastatectomy
– Not upfront unless very straightforward
– Systemic therapy as a screen
– single site (lung), long natural history