MANAGEMENT OF COLORECTAL METASTASES. Robert Warren, MD. The Postgraduate Course in General Surgery March 22, /22/2011

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1 MANAGEMENT OF COLORECTAL METASTASES Robert Warren, MD The Postgraduate Course in General Surgery March 22, 2011 Local Systemic LIVER TUMORS:THERAPEUTIC OPTIONS Hepatoma Cholangio. Neuroendo. Colorectal Melanoma Sarcoma Breast Pancreas Gastric Ovarian Others Transplantation Resection Radiofrequency ablation Microwave ablation Chemoembolization Percutaneous alcohol Systemic chemotherapy Investigational therapy Supportive care Curative Palliative Most patients with liver metastases are not candidates for resection Metastatic Colorectal Cancer: Liver Too many tumors Extrahepatic disease 1

2 Results of Hepatic Resection for Metastatic Colorectal Cancer Survival (%) Author (year) No. Pts Mortality (%) Median Survival (mos) 1-Year 5-Year 607 Gayowski et al. (199) Scheele et al. (1995) Fong et al. (1995) Jenkins et al. (1997) Jamison et al. (1997) Fong et al. (1999) 1, _ 36 Hepatectomy (n=338): Median Survival=38 months; 5 year survival = 32% HAIP placement (n=356): Median survival=16 months; 5 yr. survival= 5% Scheele et al. (2001) Choti et al. (2002) _ 6 _ Overview How Do We Define Resectable? What defines resectability, or unresectability Predictors and patterns of recurrence How can we maximize the number of patients who might benefit from metastasectomy Role of Ablation Before By what comes out How many metastases? < lesions, unilobar How large? < 5 cm resectable Extrahepatic disease? If none, resectable By what stays in Can R 0 resection (negative margins) be achieved? Can two contiguous liver segments be preserved? Can adequate future liver remnant (> 25%) be preserved? Now 2

3 Defining Candidacy for Resection Condition of hepatic parenchyma Patient health status and comorbid diseases Extent and distribution of hepatic metastatic disease (i.e. number and location of the tumors and the size of remnant liver-flr) Overview How can we maximize the number of patients who might benefit from metastasectomy Strategies to Increase the Number of Patients Eligible for Liver Resection? Reduce tumor size Chemotherapy Increase hepatic reserve Portal vein embolization Staged liver resection Mullen & Vauthey,

4 Downstaging Hepatic Metastases 13 Strategies to Increase the Number of Patients Eligible for Liver Resection? Reduce tumor size Chemotherapy Increase hepatic reserve Portal vein embolization Staged liver resection Mullen & Vauthey, 2006.

5 PVE: Increasing Hepatic Reserve Preoperative Portal Vein Embolization Should be considered in cases when the future liver remnant is too small to tolerate resection Accurate CT (or MR) volumetrics are required Ratio of future liver remnant (FLR) estimated liver volume (TELV) Indication for preoperative PVE < < 25% 30% in normal liver < < 30% 0% in steatosis/steatohepatitis < < 0% 50% in cirrhotic liver Kubota et al., 1997; Vauthey et al.,

6 PVE can be safely combined with neoadjuvant chemotherapy: 100 consecutive pts subjected to PVE at MSKCC PVE can be safely combined with neoadjuvant chemotherapy: 100 consecutive pts subjected to PVE at MSKCC Regimens varied; timing of post-pve chemoemoblization not clear Covey, et al. Annals of Surgery, Liver growth occurs after PVE even when cytotoxic chemotherapy is given No major complications occurred with PVE PVE should be considered during neoadjuvant chemotherapy to improve recovery after resection Covey, et al. Annals of Surgery, Increasing Hepatic Reserve Staged Liver Resection Overview Predictors and patterns of recurrence Image courtesy of Michael Choti, MD. 6

7 Defining Candidacy for Resection Presence of extrahepaticmetastases Prior chemotherapy, original extent of disease Quality of imaging (e.g., pre-chemo PET?, etc.) Prognosis if resected: MULTIVARIATE PREDICTORS OF RECURRENCE Hazard Coefficient p Positive Margin Extrahepatic disease > 1 tumor CEA > 200 ng/ml Size > 5 cm Node-positive primary Disease-free interval < 12 M Bilateral tumor > 0.05 Fong Y et al, MSKCC MSKCC CLINICAL RISK SCORE FOR TUMOR RECURRENCE Score yr Survival (%) 2-yr 3-yr -yr yr Median (mo)

8 Pattern of recurrence after resection of liver mets Adam, R Jarnigan et al 2010 Ann. Surgical Oncology What is the role of ablation for treating colorectal metastases? 8

9 Long-Term Outcome Following RFA in Patients With UnresectableHepatic Colorectal Metastases Outcomes Following RFA vs. Resection of Colorectal Liver Metastases 100 patients with unresectable liver mets; 2.5 months follow-up Median number = 3.5 Median size = 3.0 cm 17% complication rate 31% 5-yr OS 23% 5-yr DFS 2% 5% 9% Worse outcome with Prior chemotherapy Extrahepatic disease Percutaneous approach Median survival: 28 months Machi et al., patients (5% res, 2% RFA + res, 1% RFA alone); -yr survival of 65% vs. 36% vs. 22% Reprinted with permission; Abdalla et al., 200 9

10 Does the Approach Make a Difference? Local Recurrence Size Percutaneous (%) Laparoscopy/Laparotomy (%) < 3 cm cm cm Mulier et al., Local Recurrence Following RFA in Patients With Hepatic Colorectal Metastasis HR vs. RFA for Solitary Hepatic Metastasis (n=180) All Patients 37% local recurrence Tumors 3 cm Reprinted with permission; Aloia et al.,

11 Current Role of Ablation for Treating Colorectal Metastases? No randomized trials comparing ablation to resection Efficacy of local control appears lower than that of resection Resection remains the treatment of choice when possible in patients with hepatic colorectal metastases The goal in most cases when ablation is considered should be complete destruction with adequate margins with curative intent Guidelines for resection of colorectal at UCSF Multidisciplinary team essential Patients with solitary, multiple or bilateral mets OK Medically fit, > 25% residual, resectable extrahepatic disease Consider chemo for synchronous patients Ablation only if medically unfit Synchronous resection for synchronous mets? Duration of neo-adjuvant chemo? Stop bev early PVE helps NCCN,