Surgery in Metastatic RCC
Lee Lui ShiongSenior Consultant and Head of Department, Urology, Sengkang General Hospital
Senior Consultant, Department of Urology, Singapore General HospitalVisiting Consultant, National Cancer Centre
• Has CARMENA and SURTIME answered the question of CNx in TKI era?
• What is the role of CNx in the IO era?
Original Article
Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma
Arnaud Méjean, M.D., Ph.D., Alain Ravaud, M.D., Ph.D., Simon Thezenas, Ph.D., Sandra Colas, M.D., Jean-Baptiste Beauval, M.D., Karim Bensalah, M.D., Ph.D., Lionnel Geoffrois, M.D., Antoine Thiery-Vuillemin, M.D., Ph.D., Luc Cormier, M.D.,
Ph.D., Hervé Lang, M.D., Ph.D., Laurent Guy, M.D., Ph.D., Gwenaelle Gravis, M.D., Frederic Rolland, M.D., Claude Linassier, M.D., Ph.D., Eric Lechevallier, M.D., Ph.D.,
Christian Beisland, M.D., Ph.D., Michael Aitchison, M.D., Stephane Oudard, M.D., Ph.D., Jean-Jacques Patard, M.D., Ph.D., Christine Theodore, M.D., Christine Chevreau, M.D., Brigitte Laguerre, M.D., Jacques Hubert, M.D., Marine Gross-
Goupil, M.D., Ph.D., Jean-Christophe Bernhard, M.D., Ph.D., Laurence Albiges, M.D., Ph.D., Marc-Olivier Timsit, M.D., Ph.D., Thierry Lebret, M.D., Ph.D.,
and Bernard Escudier, M.D.
N Engl J MedVolume 379(5):417-427
August 2, 2018
Study Overview
• A randomized trial • overall survival • sunitinib alone was noninferior to sunitinib after nephrectomy • among patients with metastatic renal-cell carcinoma
• Patients had to be suitable candidates for nephrectomy….
Randomization, Treatment, and Follow-up of the Patients.
Méjean A et al. N Engl J Med 2018;379:417-427
Conclusions
• Sunitinib alone was not inferior to nephrectomy followed by sunitinib
• ….metastatic renal-cell carcinoma
• ….intermediate-risk or poor-risk disease.
• Recruitment of poor risk (almost half of cohort)
• Operating on poor risk – 16% Clavien III complications
• Using MSKCC criteria as risk stratification –what about overlaps with IMDC poor risk
• Lack of equipoise – no good risk recruited, recruitment took 9 years
What CARMENA taught us..
• Poor risk MSKCC – upfront CNx not indicated• Intermediate risk – select patients with low
metastatic burden
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)
• Hence, in the TKI era….– CNx has a definite role in good risk– Possible role in intermediate risk– No role in poor risk
Lee LS et al. 2012 Nat. Rev. Urol. Predictive models for the practical management of renal cell carcinoma
• Patients can move between risk groups depending on the prognostic score one adopts
• Eg. MSKCC intermediate risk• Can be IMDC poor risk
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 InternationalVolume 106, Issue 9, pages 1266-1269, 23 MAR 2010 DOI: 10.1111/j.1464-410X.2010.09323.xhttp://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 InternationalVolume 100, Issue 4, pages 755-759, 15 AUG 2007 DOI: 10.1111/j.1464-410X.2007.07108.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2007.07108.x/full#f1
• Majority are pre-TKI era
• Selected cohort
• Solitary lung mets benefit most
• Indolent natural history after systemic therapy
• >1 mets site – some benefit but selection of patient not clear from this series
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
Selecting patients in 2019• Cytoreductive surgery candidate• IMDC criteria / MSKCC
– Good risk– OS >12 months– symptomatic tumour– Bulk of burden in kidney– Limited metastatic sites (bone / brain mets)
• Selected intermediate risk• Not for poor risk
• Metastatectomy– Not upfront unless very straightforward– Systemic therapy as a screen– single site (lung), long natural history
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