Transcript Vascular Endothelial Growth Factor

Surgical and Ablative Strategies
for Treatment of Metastatic
Colorectal Cancer
Kim M. Olthoff, MD
Associate Professor of Surgery
Liver Transplantation and Hepatobiliary Surgery
University of Pennsylvania
Philadelphia, Pennsylvania, USA
Penn
Cancer Center
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Colorectal Cancer Demographics
 Fourth most common cancer in the United States
 Second leading cause of cancer death
– An estimated 146,940 cases will be diagnosed, with 56,700
deaths resulting from CRC
 Lifetime risk of developing CRC is 6%
 90% of CRC cases occur in patients over 50 years old
 Poor long-term survival in Stage IV disease (<5%)
 Only 40% of patients in the United States detected
through screening
Cancer Facts & Figures 2004. American Cancer Society.
Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
2
CRC Stage at Diagnosis
21.2% Stage IV
13.7% Stage I
27.9% Stage II
37.2% Stage III
Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
3
CRC: Treatment by Stage
 Stage I
– Surgery
 Stage II
– Surgery, adjuvant chemotherapy (controversial)
 Stage III
– Surgery and adjuvant chemotherapy
 Stage IV
– Primary chemotherapy; resection of metastatic
disease when possible
Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
4
Colorectal Metastases to the Liver
 The most common site of metastases from CRC
 50%-75% of patients with advanced CRC
will develop liver metastases
 15%-25% of patients have liver metastases at
presentation
 20%-35% of patients have metastatic disease
confined to the liver
Kemeny and Fata. J Hepatobiliary Pancreat Surg. 1999;6:39.
Seifert et al. J R Coll Surg Edinb. 1998;43:141.
Borner. Ann Oncol. 1999;10:623.
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Colorectal Cancer Metastatic to the Liver
Outline
 Surgical indications
 Surgical approaches
 Strategies to increase resectability
– Adjuvant therapy
– Ablative therapy
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Strategies for Metastatic Colorectal Cancer
Surgical Decision Making
Metastatic Disease
Assessment of Resectability
Tumor conference discussion
Resectable
Neoadjuvant
Unresectable
Surgery
?
Chemotherapy
Ablative therapy
Adjuvant
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Strategies for Metastatic Colorectal Cancer
Prognosis
1,001 Patients at MSKCC 1985-1998
< Lobe
n=370
> Lobe
n=631
All
n=1,001
Periop mortality (%)
0.5
4
2.8
Median survival (mos)
46
39
42
5 year survival (%)
40
33
37
Fong et al, Ann Surg 1999; 230:309
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Hepatectomy for Colorectal Metastases
Surgical Decision Making
Postop
Preop
Multivariate Analysis of Survival (N=1,001)
Factor
%
p
Hazard
> 1 Tumor
CEA > 200 ng/ml
Size > 5 cm
Node + primary
Dz-free interval < 1 yr
51
9
45
60
49
0.0004
0.01
0.01
0.02
0.03
1.5
1.5
1.4
1.3
1.3
Positive micro margin
Extrahepatic disease
11
9
0.004
0.003
1.7
1.7
Fong et al, Ann Surg 1999; 230:309
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Hepatectomy for Colorectal Metastases
Surgical Decision Making
Preop Clinical Risk Score Predicts Survival
Survival
Score
Median
5 year
0
1
2
3
4
5
74 months
51
47
33
20
22
60%
44
40
20
25
14
The problem with scoring:
no one preoperative factor can be used to exclude
Fong et al, Ann Surg 1999; 230:309
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Hepatectomy for Colorectal Metastases
Surgical Decision Making
Liver Metastases >4
Number
of tumors
4
N
49
5 year
survival (%)
33
5
38
22
6-8
23
19
9-20
45
14
155
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Conclusion: Take an Aggressive Surgical
And Adjuvant Therapy Approach!
Ann Surg Onc 2000; 7:643
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Hepatectomy for Colorectal Metastases
Staged vs Simultaneous Operations
Primary resection
Right colectomy
Left colectomy
LAR
APR
Liver resection
Wedge
Segmental
≥ Lobe
Staged
(n=106)
Simultaneous
(n=134)
15 (14%)
31 (29%)
49 (46%)
11 (10%)
53 (40%)
30 (22%)
46 (33%)
5 (4%)
9 (8%)
20 (19%)
77 (73%)
49 (37%)
28 (20%)
57 (43%)
p
0.001
0.001
No difference in major complications or survival
Martin et al JACS 2003; 197:233
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Hepatectomy for Colorectal Metastases
Surgical Decision Making: Laparoscopy
50
40
30
Unresectable
Disease Present
20
Identified at
Laparoscopy
%
10
0
Score < 3
Score > 3
N=57
N=45
Cancer 2001; 91:1191
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Surgical Approaches:
Intra-operative Ultrasound
Operative U/S probes (open)
T probe
Finger-grip probe
Microvascular flow probe
Open abdomen curvilinear probe
Laparoscopic U/S probes
Rigid laparoscopic probe
4-way flexible laparoscopic probe
End-fire probe
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Intra-op U/S of IVC and 3 hepatic veins
MH
V
RH
V
LH
V
IV
C
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Techniques for Dividing Liver
Parenchyma/Achieving Hemostasis
Monopolar cautery (bovie)
Blunt fracture/clips
Argon Beam Coagulator
Ultrasonic dissector (CUSA)
Harmonic scalpel
Ligasure
Endovascular stapler
Fibrin glue
Erbe Hydrojet
TissueLink Floating Ball/ DS3.0/3.5
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Surgical Approaches
Laparoscopic resection of liver tumor
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Hepatectomy for Colorectal Metastases
Advantages of laparoscopic liver surgery
 Band-aid sized incisions
 Less pain
 Shorter LOS
 No blood transfusions
 No oncological disadvantages
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Port placement: lap. resection R. lobe
5 mm
5 mm
12
mm
Old, open
incision
11 mm
5 mm
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Port Placement for Lap. resection of R. lobe tumor
X 5 mm - retractor
lesion
X
12 mm - Stapler
X 12 mm - Scope
Scissors
TissueLink
Argon
Harmonic
Suction irrig.
X
5 mm
(working)
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Laparoscopic partial R hepatic lobectomy
44 yo F, 5 cm lesion
Ideal lesion
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Hand Assisted Laparoscopic Resection
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Port sites for Lap. hand-assisted resection R. lobe tumor
lesion
X 12 mm - Stapler
X 5 mm - working
X 12 mm - Scope
Hand
port
23
No post-op pain, d/c’d home on POD #2
12
mm
5
mm
Hand
port
12
mm
5
mm
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Lap. hand-assisted L lateral segmentectomy
72 yo WM, met to liver
tumor
Cut edge of liver
tumor
Resected LLS
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Strategies to increase resectability
of liver metastases
 Portal vein embolization
 2 stage hepatectomy
 In situ and ex vivo resection
 Downstaging chemotherapy
– 5-FU with leucovorin or folinic acid
– Irinotecan hydrochloride (CPT-11)
– Oxaliplatin
 Local ablation techniques
– Cryotherapy, RFA
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Survival Outcomes in CRC Patients With Liver Metastasis:
Role of Neoadjuvant Irinotecan- or Oxaliplatin-Based Therapy
100
% Survival
80
58/77 patients had complete resection
60
77 patients resected (complete and partial)
after chemotherapy
40
20
74 nonoperative patients
0
0
1
2
3
4
5
6
7
8
9
Years
CRC Patients With Liver
Metastasis
(n=151)
CRC Patients With Resected
Liver Metastasis after downstaging
(n=77)
5-y survival (%)
28
50
Median OS (mo)
24
48
Topham and Adams. Semin Oncol. 2002:29:3.
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Hepatic Resection of Colorectal Metastases
Strategies to increase resectability: Ablation
 Goals of Ablation in metastatic CRC
– Prolong survival
 No proven benefit (yet)
– Treat unresectable disease
 Makes us feel like we did something
– In combination with resection
 To clear positive or narrow margin
 To ablate residual tumor
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Hepatic Resection of Colorectal Metastases
Strategies to increase resectability: Ablation
 Experience still limited in downstaging process
 No good studies to confer benefit or increase
resectability rates
 Wallace et al Surgery 1999 – Cryotherapy with
surgery. Two-thirds recurrence by 2 years.
 Pawlik et al ASO 2003 – combined RFA with
surgical resection in 172 patients. Median f/u 21
months – 56% recurrence
 RFA with less EBL, shorter LOS, but longer ablation
times, higher recurrence for large lesions (> 3 cm)
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Hepatic Resection of Colorectal Metastases
Strategies to increase resectability
 Conclusions
– Be aggressive in your approach
– Consider preoperative adjuvant
chemotherapy to increase resectability rates
– Utilize ablative techniques as a complement
to surgical resection when able to
completely eradicate viable tumor
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