1. Management of Colorectal Liver Metastasis
Joint Hospital Grand Round
Dr. Edgar Lau
Department of Surgery, PYNEH
12/1/2008

2. Background
Liver metastasis is most frequently seen in patient with colorectal carcinoma
15-25% present at the time of diagnosis
Additional 20-25% develop metachronous hepatic tumors
In 30%, liver is the only site of metastatic disease

3. Background Carries a dismal prognosis without intervention
5-year survival 0-2%
Median survival 6-12 months

4. Treatment Modalities Surgery Local Ablative Therapy Chemotherapy
Radiofrequency ablation
Chemotherapy

5. Surgery
Hepatic resection remains the only hope for cure in metastatic colorectal carcinoma
Large series from 1960s through mid-1990s reported 5-year survival rates around 33-36%

6. Prognostic Factors
Stage, grade, nodal status of primary colorectal tumor
Disease-free interval
Number and distribution of liver metastases
Pre-operative CEA level
Extrahepatic disease
Fong Y et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 1999
Positive nodal status
Multiple tumors
Disease-free interval < 12 months
CEA level > 200 ng/mL
Tumor size > 5 cm

7. Long-term Outcome

8. Reasons for Improvement
Better patient selection
Improved anesthetic monitoring
Greater understanding of hepatic anatomy
Advances in surgical technique
Improved perioperative critical care
More effective adjuvant therapy

9. Resectability
Macroscopic and microscopic (R0) treatment of the disease is feasible with either resection alone or resection combined with RFA
Two adjacent liver segments can be spared
Vascular inflow, outflow, and biliary drainage can be preserved
Sufficient remnant liver volume (> 20% of total estimated liver volume)

10. Extent of Surgical Margin
Multiple studies have shown that clear margins are essential for long-term outcomes
Extent of margin is controversial
earlier series reported at least 1 cm
recent series have shown that survival is not associated with width of negative margin

11. Two-stage Hepatectomy
For patients with multiple hepatic colorectal metastasis who are not candidates for a complete resection by single hepatectomy
even after portal vein embolization (PVE) or downsizing by chemotherapy
Adam R et al: Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Annals of Surgery, 2000
16 patients
post-op complication higher in second stage
3-year survival = 35%; Median survival 44 months from diagnosis

12. Two-stage Hepatectomy
Done with curative intent
Future functional liver remnant resected in first stage
followed by PVE to contralateral side and allow remnant hypertrophy

13. Radiofrequency Ablation
To treat tumors which do not meet resectability criteria, but disease confined to the liver or stable extra-hepatic disease
Not as a replacement for resection
Expand the number of surgical candidates
Solbiati L et al. Percutaneous radiofrequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology, 2001
117 patients
3-year survival 46%
median survival 36 months
Only 6 studies that reported at least 3-year survival were identified, with results ranging from 37-58%
McKay et al: Current role of radiofrequency ablation for the treatment of colorectal liver metastases. BJS, 2006

14. RFA + Surgery
Abdalla EK et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal metastases. Ann Surg, 2004

15. RFA + Surgery Recurrence 4 year survivial RFA 84% RFA + resection 64%

16. Neoadjuvant Chemotherapy
Enable downstaging of unresectable tumors to potentially resectable
Masi G et al: Treatment with 5-FU/folinic acid, oxaliplatin and irinotecan enables surgical resection of metastases in patients with initially unresectable metastastic colorectal cancer. Ann Surg Oncol. 2006
74 patients
26% were able to undergo surgery
median survival 36.8 months (vs months)

17. Adjuvant Chemotherapy
Role of adjuvant chemotherapy after potentially curative resection is ill-defined
High percentage of patients with resection develop recurrence
undetectable disease likely present at time of surgery

18. Pre-op vs. Post-op Chemotherapy
Advantages
Allows time for other metastastic sites to become clinically evident
Allows for in vivo gauge of chemoresponsiveness, facilitating post-operative chemotherapy planning
Response may allow for easier resection and increased rate of negative surgical margins
Response may be a prognostic factor
Disadvantages
Tumor may progress to unresectable status
Perioperative morbidity may be increased because of hepatotoxicity of chemotherapy
Possible loss to surgical follow-up
Patient anxiety and desire to have tumor resected as soon as possible

19. Chemotherapy for Palliation
Traditional therapy include fluorouracil in addition to leucovorin
response rate from 20-30%
median survival 11.5 months
Irinotecan
higher response rate when added to traditional 5-FU/leucovorin and longer overall survival (14.8 months)
Oxaliplatin
less toxic compared to irinotecan/5-FU/leucorvorin

20. Synchronous Hepatic Metastasis
Noted in 15-20% of patients
Synchronous or delayed (8-12 weeks)
Optimal timing is not well defined
Recent studies have shown comparable hospital stay, morbidity and perioperative mortality
Martin R et al: Simultaneous liver and colorectal resections are safe for synchrous colorectal liver metastasis. J Am Coll Surg, 2003
Chua HK et al: Concurrent vs. staged colectomy + hepatectomy for primary colorectal cancer with synchrous hepatic metastasis. Dis Colon Rectum, 2004
Synchronous therapy allows earlier completion of all phases of therapy +/- adjuvant therapy initiation
Decision should be individualized based on complexity of surgery

21. Recurrence 50-60% develop recurrent liver metastasis after resection
Approximately 20-30% potentially amendable to further resection with isolated intrahepatic disease
5-year survival rates ranging from 16-41%
Same criteria as for initial hepatectomy

22. Take Home Message Surgery remains the only reliable long-term cure
Increasing number of modalities to tackle patients who are deemed “unresectable”
Treatment modalities should be tailored according to individual patients

23. Thank you