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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

PennCancer 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.

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CRC Stage at Diagnosis

13.7% Stage I

27.9% Stage II37.2% Stage III

21.2% Stage IV

Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.

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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.

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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 LiverOutline

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 ResectabilityTumor conference discussion

Resectable Unresectable

Neoadjuvant Surgery ChemotherapyAblative therapy

Adjuvant

?

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Strategies for Metastatic Colorectal Cancer

Prognosis

< Lobe > Lobe Alln=370 n=631 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

1,001 Patients at MSKCC 1985-1998

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Hepatectomy for Colorectal Metastases

Surgical Decision Making

Factor % p Hazard

> 1 Tumor 51 0.0004 1.5CEA > 200 ng/ml 9 0.01 1.5Size > 5 cm 45 0.01 1.4Node + primary 60 0.02 1.3Dz-free interval < 1 yr 49 0.03 1.3

Positive micro margin 11 0.004 1.7Extrahepatic disease 9 0.003 1.7

Pos

top

P

reop

Fong et al, Ann Surg 1999; 230:309

Multivariate Analysis of Survival (N=1,001)

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Hepatectomy for Colorectal MetastasesSurgical Decision Making

SurvivalSurvivalScore Median 5 year

0 74 months 60% 1 51 442 47 40 3 33 20 4 20 25 5 22 14

Fong et al, Ann Surg 1999; 230:309

The problem with scoring: no one preoperative factor can be used to exclude

Preop Clinical Risk Score Predicts Survival

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Hepatectomy for Colorectal Metastases

Surgical Decision Making

Number 5 yearof tumors N survival (%)

4 49 33

5 38 22

6 - 8 23 19

9-20 45 14

155 23

Ann Surg Onc 2000; 7:643

Liver Metastases >4

Conclusion: Take an Aggressive SurgicalAnd Adjuvant Therapy Approach!

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Hepatectomy for Colorectal Metastases

Staged vs Simultaneous Operations

Staged (n=106)

Simultaneous (n=134)

p

Primary resection

Right colectomy

Left colectomy

LAR

APR

15 (14%)

31 (29%)

49 (46%)

11 (10%)

53 (40%)

30 (22%)

46 (33%)

5 (4%)

0.001

Liver resection

Wedge

Segmental

≥ Lobe

9 (8%)

20 (19%)

77 (73%)

49 (37%)

28 (20%)

57 (43%)

0.001

No difference in major complications or survivalMartin et al JACS 2003; 197:233

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UnresectableDisease Present

Identified atLaparoscopy

0

10

20

30

40

50

Score < 3 Score > 3

Cancer 2001; 91:1191

Hepatectomy for Colorectal MetastasesSurgical Decision Making: Laparoscopy

N=45N=57

%

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Surgical Approaches:Intra-operative Ultrasound

Operative U/S probes (open)T probeFinger-grip probeMicrovascular flow probeOpen abdomen curvilinear probe

Laparoscopic U/S probesRigid laparoscopic probe4-way flexible laparoscopic probeEnd-fire probe

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Intra-op U/S of IVC and 3 hepatic veins

IVC

RHV

MHV

LHV

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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 ApproachesLaparoscopic 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

11 mm

5 mm

12 mm

5 mm

5 mm

Old, open incision

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Port Placement for Lap. resection of R. lobe tumor

ScissorsTissueLinkArgonHarmonicSuction irrig.

X

X 12 mm - Scope

12 mm - Stapler

5 mm(working)

X

5 mm - retractor

X

lesion

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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

lesionX

X 12 mm - Scope

Hand port

X

12 mm - Stapler

5 mm - working

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No post-op pain, d/c’d home on POD #2

12 mm

12 mm

5 mm

5 mm

Hand port

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Lap. hand-assisted L lateral segmentectomy

72 yo WM, met to liver

tumor Resected LLS

Cut edge of liver

tumor

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Strategies to increase resectabilityof 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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77 patients resected (complete and partial) after chemotherapy

58/77 patients had complete resection

Topham and Adams. Semin Oncol. 2002:29:3.

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

Survival Outcomes in CRC Patients With Liver Metastasis:

Role of Neoadjuvant Irinotecan- or Oxaliplatin-Based Therapy

0 1 2 3 4 5 6 7 8 9

Years

0

20

40

60

80

100%

Su

rviv

al

74 nonoperative patients

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Hepatic Resection of Colorectal MetastasesStrategies 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 MetastasesStrategies 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 MetastasesStrategies 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