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

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 Chemotherapy 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 4 year survivial RFA 84% RFA + resection 64%

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 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

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

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