Management of Colorectal Liver Metastasis

Joint Hospital Grand RoundDr. Edgar Lau

Department of Surgery, PYNEH12/1/2008

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

Background

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

Treatment Modalities

Surgery

Local Ablative Therapy Radiofrequency ablation

Chemotherapy

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%

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

Long-term Outcome

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

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)

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

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

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

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

RFA + Surgery Abdalla EK et al. Recurrence and outcomes following

hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal metastases. Ann Surg, 2004

RFA + Surgery Recurrence

RFA 84% RFA + resection 64% Resection 52%

4 year survivial RFA 22% RFA + resection 36% Resection 65%

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. 22.2 months)

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

Pre-op vs. Post-op ChemotherapyAdvantages 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

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

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

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

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

Thank you