Transcript Colorectal liver metastasis Mx

Management of colorectal cancer with
liver metastasis
Dr. Vivian Lee
Department of Surgery, UCH
Incidence
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UP to 70 % of patients with colorectal cancer
develop liver metastasis during the course of their
disease
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50% are isolated liver metastasis
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25% are synchronous
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5-10% resectable
Cady B, et al. Arch Surg 1992
Natural history
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Untreated patient
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open-and-close cases
Median survival 6-12 months
Bengmark S, et al. Cancer, 1969
Treatment
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Direct lesional approach
 Surgical
 Local ablative therapy
Systemic approach
 Systemic chemotherapy
Vascular approach
 Intraarterial infusion of chemotherapy
Surgical treatment is the gold
standard for isolated liver metastasis !
Surgical treatment
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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.
Surgical treatment
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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
Operative mortality
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personal series
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247 cases over 12 years
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operative mortality: < 5%
Fortner JG, et al. Ann Surg. 1984
Surgical resection – early experience
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Multi-institutional review
859 patients of 24 centers
5-year survival 33%
5-year disease-free survival 21%
Surgery 1998; 103: 278-288.
Major contraindications
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Positive perihepatic lymph nodes
Presence of resectable extrahepatic
metastasis
Presence of 4 or more metastasis
Surgery 1988; 103: 278-288.
Conditions with poor survival
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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.
Survival rate nowadays
surgical
survival
Study
N
mortality
1y%
3y%
5y%
10y%
Butler
62
10
_
50
34
21
Nordlinger
80
5
5
41
25
16
Scheele
219
6
_
_
39
21
Scheele
469
4
_
45
38
23
Jamison
280
4
84
46
27
20
Fong, 99
1001
3
89
57
37
22
overall
2111
35.6% 21.6%
Predictors of poor long-term outcome
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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
Recurrence after hepatectomy
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50% develop another liver metastasis
Half of them develop extrahepatic
metastasis
How could this be treated?
Repeat liver resection for recurrence ?
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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.
How can we prevent recurrence after surgery?
Hepatic artery chemotherapy
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implantable pump connected to
intra-arterial catheter, GDA
Complications
 Hepatic toxicity
 Peptic ulcer
Hepatic artery chemotherapy
HAI after hepatectomy
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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)
HAI after hepatectomy
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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)
Local Ablative Therapy
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Radiofrequency ablation
 Several advantages over cryotherapy
 Can be performed percutaneously
 Evenly distributed heat, unlike the ice
ball formation
Local Ablative Therapy
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RFA Disadvantage
 Limited by the size, up to 3 or 4cm only
 Complete ablation rate
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HCC:
Metastasis:
86%
11%
T Kaneko, et al. HBP, 2003
Radiofrequency ablation
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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
Is RFA with HAI feasible?
RFA and HAI
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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
How can we treat systemic spread after
surgery?
Systemic Chemotherpy
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Treat the entire patient
Low response rates with short duration of
response
Treated with chemotherapy
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64 cases
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I.A. or I.V. 5-fluorodeoxyuridine
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Median survival 12-18 months
Chang AE, et al. Ann Surg, 1987
Chemotherapy for metastatic colorectal
carcinoma
First line chemotherapy
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5FU + Leucovorin
meta-analysis:
 response rate 23%
vs 11% for 5FU alone
no impact on overall survival
Second line chemotherapy
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Irinotecan (CPT 11)
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inhibit topoisomerase I
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just completed phase II study
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tumor growth control: 60%
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Gil-Delgado MA, American Journal of Clinical
Oncology, 2001
Summary
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Surgical resection is the gold standard.
Survival improves by post-operative
hepatic arterial chemotherapy.
Post-operative systemic chemotherapy is
needed to cover micro-metastasis.