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

Lee.lui.shiong@singhealth.com.sg

Disclosures

• Advisory board

– Janssen

– Bayer

– MSD

– BMS

• Clinical trial funding

– Janssen

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

• Phase III

• CN+Sutent vs Sutent alone

• sunitinib - 50 mg daily , 28 on /14 off every 6 weeks

• primary end point overall survival

Planned n=576

• 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

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

Utilisation of CN

Tsao, C et al. World J Urol (2013) 31: 1535

Poor risk have limited incremental OS benefit

with CN

No CN CN

• Good prognosis – zero

• Intermediate – 1- 2

• Poor - ≥3

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)

Lee LS et al. 2012 Nat. Rev. Urol. Predictive models for the practical management of renal cell

carcinoma

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

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

Immediate versus deferred nephrectomy

Recruitment closed

Sunitinib

Primary outcome PFS

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

Metastatectomy

J Urol

• 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

Making Cytoreductive surgery safer

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

• N=25

• Sunitinib n=12, others n=13

• 84% stable thombi level

• 4% (n=1) increase

• 12 % (n=3) decrease, median 1.5 cm

Figure 1. OS following upfront surgery (M1 cohort)Clavien III and above (12%)

MVA -Atrial thrombus predictive of surgical complications

Reducing surgical morbidity

• Patient selection is the key!!!

• Minimally invasive techniques if possible

• Optimise the patient

• No “occasional go” surgeon

Alternatives to surgery

• Embolisation

• Radiation therapy

• Analgesia

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