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Carcinome Hépatocellulaire : Résection ou Transplantation pour un CHC de petite taille

Petit CHC : le Pr René Adam (AP-HP Hôpital Paul Brousse, France) indique les recommandations pour transplantation dans le cas d'un petit CHC.

1 of 51
Hôpital Paul Brousse
Université Paris-Sud
René Adam
Resection or Transplant as 1st line treatment ?
What are the Keys of Decision ?
LRLT vs Resection. Lee et al L Surg Oncol 2009
OS DFS
When comparing the results DFS : a major item…
What are the Keys of Decision ?
1- DFS more than OS…
Surgical Resection vs. Transplantation
Yamamoto J et al. Cancer 1999;86:1151
When comparing the results 10-Yr Survival mandatory…
OS DFS
Hepatectomy
Transplantation

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Carcinome Hépatocellulaire : Résection ou Transplantation pour un CHC de petite taille

  • 1. Hôpital Paul Brousse Université Paris-Sud René Adam Resection or Transplant as 1st line treatment ?
  • 2. What are the Keys of Decision ?
  • 3. LRLT vs Resection. Lee et al L Surg Oncol 2009
  • 4. OS DFS When comparing the results DFS : a major item…
  • 5. What are the Keys of Decision ? 1- DFS more than OS…
  • 6. Surgical Resection vs. Transplantation Yamamoto J et al. Cancer 1999;86:1151 When comparing the results 10-Yr Survival mandatory… OS DFS Hepatectomy Transplantation
  • 7. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years…
  • 8. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years… 3- Cirrhosis or not Cirrhosis ?
  • 9. Study Flow • Local Ablation n = 1,550 • Segmental Resection n = 703 • Lobectomy (incl. extended resection) n = 619 • Transplant n = 1,117 16,209 Patients with HCC in SEER Database (2004-2007) 3,989 Patients Include only patients who underwent surgical treatment. Exclude patients with metastatic disease, no staging data.
  • 11. Overall Survival with Minimal Fibrosis
  • 12. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years… 3- Cirrhosis or not Cirrhosis ? 4- Within Milan or Beyond ?
  • 13. Within Milan Beyond Milan A large difference in DFS !… No difference at all !…
  • 14. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years… 3- Cirrhosis or not Cirrhosis ? 4- Within Milan or Beyond ? 5- Comparative results
  • 15. Study N 5-year survival Mortality (%) Iwatsuki (2000) 344 49 % – Tamura (2001) 53 61 % – Hemming (2001) 112 57 % 13 Jonas (2001) 120 59 % 1.7 Figueras (2001) 307 63 % – Yao (2001) 60 75 % 1.4 Todo (2004) 316 69 % (3-y ) – Gondolesi (2004) 36 45 % 22 Zavaglia (2005) 155 72 % 11 Takada (2006) 93 64 % – Cherqui (2009) 18a 70 %b 0 Lee (2010) 78 68 % 5.1 Coelho (2009) 45 4 recurrences 0 a Salvage transplantation after resection b From time of transplantation Selected series of Liver Transplantation for Hepatocellular Carcinoma since 2000
  • 16. Study N 5-year survival (%) Mortality (%) ____________________3540___________________________________________ Zhou (2001) 1000 63 1.5 Grazi (2001) 264 42 4.9 Yamamoto (2001) 58 62 – Poon (2002) 135 70 3.7 Wayne (2002) 249 41 – Grazi (2003) 308 42 4.9 Ercolani (2003) 224 42 – Hu (2005) 154 – – Pawlik (2005) 300 27 5 Wu (2005) 161 (1991-96) 28 3.7 265 (1997–02) 34 0.4 Taura (2007) 166 46 4 Yamashita (2007) 59 71 – Cherqui (2009) 67 72 4.5 Lee (2010) 130 52 0.8 Selected series of Hepatic Resection for Hepatocellular Carcinoma since 2000
  • 17. 49,43% 62,09% Mean 5-year survival (Resection vs Liver transplantation) Selected series published since 2000 with 5-y survival available 1376 patients (11 series) 3386 patients ( 14 series) P = 0.02
  • 18. 6,7% 3,3% Postoperative Mortality (Resection vs Liver transplantation) Selected series published since 2000 with PO mortality available 624 patients (8 series) 2780 patients (10 series) p=0.28
  • 19. 1. What are the respective results of Resection and LT for Small Single HCC (up to 5cm) ? 2. Is there a cut-off size for which Resection could be preferred to LT ? Adam et al, Ann Surg 2012
  • 20. Consecutive series of 97 Resections and 101 LT for: - Single HCC up to 5 cm - in cirrhotic patients - Operated by the same surgical team Potential bias : more Child B/C expected in the LT group: - Would penalize Transplantation compared to Resection - No influence on the tumor outcome « per se » (recurrence not influenced by liver function status…) Resection vs LT in Small HCC Paul Brousse Hospital 1990-2010
  • 21. VARIABLES GROUP R n = 97 GROUP T n = 101 p value Post Operative death (up to 2 months) Yes 4 (4.1%) 3 (3%) 0.72 Post Op Complications ≥ Grade 3 Clavien 18 (19.1%) 24 (24.7%) 0.35 Tumour recurrence Yes 60 (61.9%) 10 (10.9%) < 0.0001 Site of tumour recurrence Hepatic Extrahepatic Hepatic and Extrahepatic 49 (50.5%) 2 (2.1%) 9 (9.3%) 3 (3%) 5 (5%) 2 (2%) 0.33 Present Status Alive Alive without Disease 54 (55.7%) 26 (26.8%) 59 (58.4%) 55 (54.5%) 0.7 < 0.0001 Post operative Outcome Resection vs Transplantation for Single HCC ≤ 5 cm on Cirrhosis
  • 22. Survival for Single HCC ≤ 5 cm on Cirrhosis Overall Survival Disease-Free Survival Adam et al, Ann Surg 2012
  • 23. FACTOR AND GROUPS OVERALL PATIENT COHORT p value RR CI 95% ALL PATIENTS (n = 198) Overall Survival Resection group Maximum Diameter of nodule at diagnosis ≥ 3 cm Microvascular Invasion Disease free survival Resection group Maximum Diameter of nodule at diagnosis ≥ 3 cm Microvascular Invasion 0.002 0.0003 0.005 < 0.0001 0.0004 0.02 2.15 2.41 1.95 4.88 2.02 1.56 [1.32 ; 3.48] [1.5 ; 3.87] [1.23 ; 3.09] [3.11 ; 7.66] [1.37 ; 2.99] [1.06 ; 2.31] Multivariate analysis in patients who underwent resection (n = 97) or transplantation (n = 101) for single HCC on cirrhotic liver up to 5 cm diameter
  • 24. Is there a cut-off size for which Resection is at least equivalent to Transplantation ?
  • 25. Survival for Solitary HCC 3-5 cm on Cirrhosis Overall Survival Disease-Free Survival Adam et al, Ann Surg 2012
  • 26. FACTOR AND GROUPS OVERALL PATIENT COHORT p value RR CI 95% ALL PATIENTS (n = 77) Overall Survival Resection group Microvascular invasion Disease free survival Resection group Microvascular invasion 0.0006 0.0042 < 0.0001 0.0196 3.59 2.34 6.96 1.83 [1.73 ; 7.44] [1.31 ; 4.19] [3.22 ; 15.04] [1.1 ; 3.03] Multivariate analysis in patients who underwent resection (n= 51)or transplantation (n = 35) for single HCC on cirrhotic liver 3-5 cm diameter
  • 27. Survival for Solitary HCC ≤ 3 cm on Cirrhosis Overall Survival Disease-Free Survival Adam et al, Ann Surg 2012
  • 28. FACTOR AND GROUPS OVERALL PATIENT COHORT p value RR CI 95% ALL PATIENTS (n = 114) Overall Survival Resection group Age > 60 Period before 2000 Disease free survival Resection group - 0.0049 0.0086 < 0.0001 - 2.78 2.72 4.35 - [1.36 ; 5.67] [1.29 ; 5.74] [2.39 ; 7.92] Multivariate analysis in patients who underwent resection (n= 47)or transplantation (n = 68) for single HCC on cirrhotic liver < 3 cm diameter
  • 30. 2011
  • 31. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years… 3- Cirrhosis or not Cirrhosis ? 4- Within Milan or Beyond ? 5- Comparative results 6- Equity of access to cure with Salvage ?
  • 32. Salvage transplantation : the solution ?
  • 33. Resection as a bridge to LT 2 different situations… Decision LT Resection LT « Bridge » LT « Salvage » LT Resection 1st Recurrence LT
  • 34. Resection and Salvage LT ? Adam and coll, Ann Surg 2003 Overall Survival Disease-free Survival
  • 35. Belghiti et al, Ann Surg 2003 Resection as a Bridge / Salvage to LT ? Cherqui et al, Ann Surg 2009 Bridge Salvage
  • 36. Log rank p= 0.17 73% 70% 68% 53% 84% 88% Primary LT : 349 Secondary LT : 33 Secondary vs Primary Transplantation for HCC Overall Survival
  • 37. Secondary vs Primary Transplantation for HCC Disease-free Survival Log rank p= 0.015 70% 51% 65% 43% 81% 75% Primary LT : 349 Secondary LT : 33
  • 38. Yes because: More technical challenging Increased risk of recurrence Decreased disease-free survival Liver Resection: a risk for secondary LT ?
  • 39. Is recurrence after Resection always suitable for Transplant ?
  • 40. Resection 2nd LT 1st LT Decision LT Decision LT Drop out Recurrence Out of Milan criteria Life-threatening GI Bleeding Infected Ascites Liver Failure Drop out CANDIDATES ELECTED
  • 41. Author Adam Margarit DelGaudio Cherqui Fucks Present S Country France Spain Italy France France France Year 2003 - 2008 2009 2010 2011 Res / Rec 98 /75 37 80 / 39 67 / 36 118 / 90 117/ 91 % LT 23% 27% 26% 61% 43% 36% LT after Liver resection : A low transplantability rate overall…
  • 42. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. 26% Transplantability rate of recurrence ! 12.5% Transplantability rate of all LR !
  • 43. Transplantability rate is much lower in practice than it is theoretically expected : Up to 50% of patients could loose the chance to be transplanted… Transplantability after Resection The reality…
  • 44. « This low salvage rate may represent a lost opportunity for a number of patients who, had they received a primary transplant may have had better long term survival. For these patients the potential for cure has been lost » « Therefore, if we are going to propose resection to the patient with HCC and cirrhosis we are potentially treating the patient with an option that gives this patient a greater chance of recurrence and a questionable overall survival when compared to primary liver transplantation »
  • 45. Resection with possible LT vs Primary LT Overall Survival 68% 59% 56% 32% 88% 84% Log rank test, p<0.0001 Primary LT : 352 Primary resection ± LT : 115 From the time of LR From the time of LT
  • 46. Resection with possible LT vs Primary LT Disease-free Survival at last follow up 65% 31% 54% 20% 82% 70% Log rank test, p<0.0001 Primary LT : 352 Primary resection ± LT : 115
  • 47. Multivariate Analysis on Patients Eligible for Transplant Resected or Transplanted (n=466) RRP IC 95% Overall survival Disease-free survival No nodules > 3 2.030.0008 Max size > 30 mm 1.710.002 [1.34 ; 3.08] [1.22 ; 2.40] Resection + LT 1.910.02 [1.11 ; 3.28] No nodules > 3 1.710.02 Max size > 30 mm 1.770.002 [1.09 ; 2.67] [1.24 ; 2.52] Resection + LT 1.910.02 [1.11 ; 3.28]
  • 48. What are the Keys of Decision ? 1- DFS more than OS… 2- Survival at 10 years more than at 5 years… 3- Cirrhosis or not Cirrhosis ? 4- Within Milan or Beyond ? 5- Comparative results 6- Equity of access to cure with Salvage ? 7- Could organ shortage justify all strategies ?
  • 49. Shortage of Organs… 1- A living donor could sometimes be available… 2- Even not available, results of LT for HCC within Milan criteria are as good as that of Benign disease So…. Why to penalize patients with transplantatble HCC precluding 80% of them from a possibility of long term survival if not cure ?… Yes but…
  • 50. et al
  • 51. CONCLUSIONS 1- Although liver resection may provide good survival benefit to hyperselected patients, LT is overall the best option at long term and on a disease-free basis 2- Resection provides similar survival only for single HCC< 3 cm with however a lower disease-free survival compared to LT 3- Salvage transplantation is not the solution since a significant proportion of pts loose the chance to be transplanted… 4- Provided that the survival benefit of HCC patients is similar to that of ESLD, there is no ethical reason to discriminate HCC…