Management of colorectal cancer with liver metastasis

1. Management of colorectal cancer with liver metastasis Dr. Vivian Lee Department of Surgery, UCH

2. Incidence • UP to 70 % of patients with colorectal cancer develop liver metastasis during the course of their disease • 50% are isolated liver metastasis • 25% are synchronous • 5-10% resectable Cady B, et al. Arch Surg 1992

3. Natural history • Untreated patient • open-and-close cases • Median survival 6-12 months Bengmark S, et al. Cancer, 1969

4. Treatment • Direct lesional approach • Surgical • Local ablative therapy • Systemic approach • Systemic chemotherapy • Vascular approach • Intraarterial infusion of chemotherapy

5. Surgical treatment is the gold standard for isolated liver metastasis !

6. Surgical treatment • Prerequisites: • Medical fittness for major surgery • No sign on preoperative imaging of disseminated disease • Tumors anatomically confined within liver such that adequate liver parenchyma could be preserved.

7. Surgical treatment • 122 cases (74 metachronous lesions) over 8 years • postoperative complication: 20 % • pneumonia, pleural effusion • hepatic insufficiency • bile leak and biliary fistula Schlag P, et al. Eur J Surg Oncol, 1990

8. Operative mortality • personal series • 247 cases over 12 years • operative mortality: < 5% Fortner JG, et al. Ann Surg. 1984

9. Surgical resection – early experience • Multi-institutional review • 859 patients of 24 centers • 5-year survival 33% • 5-year disease-free survival 21% Surgery 1998; 103: 278-288.

10. Major contraindications • Positive perihepatic lymph nodes • Presence of resectable extrahepatic metastasis • Presence of 4 or more metastasis Surgery 1988; 103: 278-288.

11. Conditions with poor survival • Margin of resection < 1 cm • Positive mesenteric LN in primary tumor specimen • Disease-free survival < 1 year NB. Presence of any one of these factors is not contraindication for surgery. Surgery 1988; 103: 278-288.

12. Survival rate nowadays

13. Predictors of poor long-term outcome • 1001 consecutive cases from 1985 to 1998 • multivariate analysis • positive margin • node-positive primary • extrahepatic disease • disease-free interval from primary to metastasis < 12 month • number of hepatic tumor > 1 • largest hepatic tumor > 5 cm • CEA level > 200 ng/ml Fong Y, et al. Ann Surg, 1999

14. Recurrence after hepatectomy • 50% develop another liver metastasis • Half of them develop extrahepatic metastasis • How could this be treated?

15. Repeat liver resection for recurrence ? • 130 patients with 143 repeat liver resections(14 had both liver and extra-hepatic) • Operative mortality 0.9% • 3-year survival 33% • 12 patients had the 3rd liver resection→ mean survival 12.5 months Nordlinger B, et al. J Clin Oncol 1994.

16. How can we prevent recurrence after surgery?

17. Hepatic artery chemotherapy • implantable pump connected to intra-arterial catheter, GDA • Complications • Hepatic toxicity • Peptic ulcer

18. Hepatic artery chemotherapy

19. HAI after hepatectomy • Memorial Sloan- Kettering Cancer Center Trial • Intrahepatic chemotherapy verse systemic chemotherapy after surgery • 2 years survival : 86% vs 72%(p=0.03) • Hepatic 2 years disease free survival: • 90% vs 60 %( p<0.001)

20. HAI after hepatectomy • Southwest Oncology Group study • Surgery vs HAI after surgery • 4-yr hepatic disease-free survival • 43% vs 66.9% ( p=0.03) • 4-yr overall disease-free survival • 25.2% vs 45.7% ( p=0.04) • 4-yr overall survival • 52.7% vs 61.5% ( p=0.06)

21. Local Ablative Therapy • Radiofrequency ablation • Several advantages over cryotherapy • Can be performed percutaneously • Evenly distributed heat, unlike the ice ball formation

22. Local Ablative Therapy • RFA Disadvantage • Limited by the size, up to 3 or 4cm only • Complete ablation rate • HCC: 86% • Metastasis: 11% T Kaneko, et al. HBP, 2003

23. Radiofrequency ablation • Prospective non randomized trial • 123 patient • HCC: 39.1% • Colorectal liver metastasis: 49.6% • Only 1 patient with local recurrence Curley SA, Ann Surgery. 1999

24. Is RFA with HAI feasible?

25. RFA and HAI • Prospective non randomized study • 50 patient treated with RFA and HAI with or without resesction • Follow up: 20 months • 32% patient remained disease free • 30% developed new liver metastasis • 48% developed extrahepatic disease Curley SA, Ann Surg Oncol. 2003

26. How can we treat systemic spread after surgery?

27. Systemic Chemotherpy • Treat the entire patient • Low response rates with short duration of response

28. Treated with chemotherapy • 64 cases • I.A. or I.V. 5-fluorodeoxyuridine • Median survival 12-18 months Chang AE, et al. Ann Surg, 1987

29. Chemotherapy for metastatic colorectal carcinoma

30. First line chemotherapy • 5FU + Leucovorin • meta-analysis: • response rate 23% vs 11% for 5FU alone • no impact on overall survival

31. Second line chemotherapy • Irinotecan (CPT 11) • inhibit topoisomerase I • just completed phase II study • tumor growth control: 60% • Gil-Delgado MA, American Journal of Clinical Oncology, 2001

32. Summary • Surgical resection is the gold standard. • Survival improves by post-operative hepatic arterial chemotherapy. • Post-operative systemic chemotherapy is needed to cover micro-metastasis.