1. Oliver Hakenberg Urologische Klinik und Poliklinik Universitätsklinikum Rostock Surgical treatment of renal cell carcinoma with caval thrombus

2. Tumor stage 90% 70% 35% 15% 5-year survival after surgery

3. Cava tumour extension

4. Mayo Clinic classification Classification Level Irenal or < 2cm IVC Level IIinfrahepatic Level IIIretrohepatic Level IVatrial Neves & Zincke, Brit J Urol 1987 50% 10%40% TNM T3bbelow diaphragm T3cabove diaphragm

5. Caval thrombus TEE transesophageal ultrasound MRI Duplex venous sonography cavography not necessary

6. Caval thrombus Renal vein vena cava kidney

7. Removal of suprahepatic caval thrombus cavotomy

8. Specimen after nephrectomy and resection of caval thrombus Rim of renal vein

9. Presentation  Up to 10% of patients with RCC (1990s)  majority right-sided (85%)  majority have symptoms –IVC syndrome –edema –cardiac dysfunction –abdominal pain –hematuria

10. Surgical technique  Exposure –Chevron bilateral subcostal –Median laparotomy with sternotomy  Standard –isolation of vena cava –extended hepatic mobilization –PRINGLE maneuver –Primary or patch closure of vena cava  Alternative –Endoluminal occlusion –Resection of vena cava  Cardiac bypass  Resection of vena cava/prosthetic interposition

11. Endoluminal caval occlusion  Through inferior vena cava –blind –transesophageal echography-guided  Through jugular vein –preoperatively

12. Surgical technique: endoluminal occlusion n=31 level II or III 2000-2005 Follow-up 22.1 months n= 131 splenectomy 1 thrombosis IVC n=7 M+ Avoids suprahepatic approach No complications due to endoluminal occlusion No air embolism Zini et al, BJU Int, 2006  Through inferior vena cava –blind –transesophageal echography-guided  through jugular vein –preoperatively

13. Intraatrial thrombectomy  Standard –Cardiopulmonary bypass with hypothermia  Alternative –mild hypothermia, cardiopulmonary bypass –beating, perfused heart –n= 6, no mortality (Chowdury et al, 2006) –venous cardiac bypass (superior vena cava + infrarenal vena cava) –endoluminal occlusion via cavotomy at renal vein level –N= 6, 1 postoperative death (Modine et al, 2007) Chowdhury et al, Ann Thorac Surg 2007 Modine et al, Int J Surg 2007

14. Interruption of vena cava  n=40 patients with vena cava interruption at surgery  Postoperative venous disability score –None class 3 –12/40 (30%) class 2 –12/40 (30%) class 1 – 16/40 (40%) no disability Blute et al, J Urol 2007

15. Perioperative mortality 3-16% n =Perioperative mortality Bissada et al, 200375n= 48 without M+2% (1) n= 26 with M+7% (2) Kaplan et al, 2002119.1% (1) Zini et al, 20051010% (1) Galluci et al, 2004150% Bastian et al, 200527n=8 with N+ Parekh et al, 2005498% (4) Bissada et al, Urology 2003 Kaplan et al, Am J Surg 2002 Parekh et al, J Urol 2005 Bastian et al, Eur J Surg Oncol 2005

16. Surgical series n= 63 1993-2003 5-yr-disease-free survival infrahepatic 35 Retrohepatic 20 Suprahepatic 5 Atrial 3 48.5% 50.6% 66.6% 40% operative mortality 3% complications 34% (conservative) Perinephric fat invasion yes no 31% 68%p<0.01 pN positive negative 30% 60.9% p<0.05 Kulkarni et al, Indian J Cancer 2007

17. Prognosis with treatment N+M1N0M0 2-year- survival N0M0 5-year survival n= 107 RCC with renal vein or vena cava thrombus 26%54% Vena cava83%72% Renal vein90%68% n= 100 RCC without 12%31%93%81% Prognostic factors: capsular penetration collecting system invasion extension into hepatic veins Zisman et al, J Urol 2003

18. Prognosis of surgery in non-metastatic RCC n3-year cancer- specific survival 5-yr overall survival 10-year overall survival Skinner, 19894357% Glazer, 19961857% Moinzadeh, 200415366% (renal vein) Kim, 200481renal vein 36% IVC 35% T3c 12% Lubahn, 20064456% Ciancio, 20075653% Skinner et al, Ann Surg 1989; Glazer et al, J Urol 1996; Moinzadeh et al, J Urol 2004; Kim et al, J Urol 2004; Lubahn et al, J Thora Cardiovasc Surg 2006; Ciancio et al, Eur Urol 2007

19. Impact of level of thrombus on survival? n5-yr overall survival 10-year overall survival Impact on survival Skinner, 198956Level I 35% Level II 18% Level III 0% yes Glazer, 199618Level III 60% Level IV 57% no Moinzadeh, 2004153Level not associated with local stage Level 1 66% Level II-IV 29% ? Kim, 2004221Level IV much worse than Level I/II yes Skinner et al, Ann Surg 1989; Glazer et al, J Urol 1996; Moinzadeh et al, J Urol 2004; Kim et al, J Urol 2004;

20. Prognosis with cytoreductive treatment in M1 disease M1 patients2-year- survival 5-year survival Nephrectomy + immunotherapy 52%41% nephrectomy45%32% immunotherapy13%0% No treatment0% Zisman et al, J Urol 2003

21. Impact of thrombus removal in metastatic RCC  30% of patients with IVC thrombus have M+ disease  patients are symptomatic  surgery is palliative: quality of life  cytoreductive surgery improves response to immunotherapy  impact of targeted therapies?

22. Outcome n= 134 FU 16.4 months median nMedian survival (months) Radical nephrectomy with thrombectomy 11119.8 N0M0: 51.7 NxM1: 6.9 ImmunoRx With 13.5 Without 5.1 Embolization + immunotherapy 236.9 Prognostic factors: localized tumour stage N0M0 vs N+M0, NxM1 Fuhrmann grades1 and 2 vs 3 and 4 thrombus levelI and II vs III and IV Haferkamp et al, J Urol 2007

23. Outcome nn (M+)Follow-up (months) DODAlive with M+Alive and NED Bissada et al, 2003 752624 (41%)22 (47%) Kaplan et al, 2002 1171.4% estimated survival at 10 years Zini et al, 200510 2 Galluci et al, 2004 15531 Bastian et al, 2005 278112 (7%)11 (40%) Parekh et al, 2005 49158 (16%)29% (14)21 (43%) Bissada et al, Urology 2003 Kaplan et al, Am J Surg 2002 Galluci et al, Eur Urol 2004 Parekh et al, J Urol 2005 Bastian et al, Eur J Surg Oncol 2005

24. Conclusions  thrombus carries worse prognosis because local prognostic indicators are worse  overall survival with R0 resection is > 50%  Level of thrombus –increases difficulties of surgery –probably correlates with reduced survival –increases the risk of recurrence  Surgery in non-metastatic disease improves survival  Surgery in metastatic disease –improves survival –is palliative –cytoreduction improves results of adjuvant therapy