Scope of the Problem Liver Disease Should be Resected First (with - - PowerPoint PPT Presentation

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Synchronous Hepatic Colorectal Metastases: Liver Disease Should be Resected First (with the primary tumor)

William R. Jarnagin, MD, FACS

Scope of the Problem

• Colorectal cancer in USA
• New cases

150,000

• Metastatic liver disease

75,000

Synchronous presentation

20,000*

Liver-only disease

7,000§

* - may vary depending on definition used § - candidates for potentially curative resection

Definitions

• Synchronous liver disease
• Identified at time of 1o diagnosis

? Within 12 months

• Primary tumor
• Asymptomatic

No obstruction, no bleeding

• Liver disease
• Resectable with one procedure

Staged resection not required ? Ablation plus resection

• Not found incidentally during 1o resection

Synchronous Colorectal Liver Metastases

Historical approach

• Resect the primary lesion
• Even if asymptomatic

‘To avoid bleeding or obstructive complications’

• Treat with chemotherapy
• Infrequently consider surgery for the liver disease
• ‘Synchronous disease carries a high risk for recurrence’

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Synchronous Colorectal Liver Metastases

Contemporary approach

• The primary tumor
• Infrequently requires resection due to symptoms
• Considered in the context of overall disease management
• Chemotherapy
• Should be part of the treatment plan
• Should not be a knee-jerk reflex to treat before resection

High risk patients likely to benefit most

• Should always consider surgery if resectable
• Synchronous disease does not preclude long-term survival

Synchronous Colorectal Liver Metastases

• Complete resection of all disease
• Should be the objective
• One operation is better than 2
• Morbidity/resource utilization related to both operations

Additive

• All studies retrospective
• Significant bias
• Colorectal resection first in nearly all staged procedures

Staged (n=160) Synchronous (n=70) p Age (years) 61 58 0.06 Comorbidities Cardiac Pulmonary Diabetes Hypertension 86% 5% 10% 33% 87% 3% 18% 34% 0.8 0.4 0.2 1.0 # Liver Tumors 3 (1-8) 3 (1-16) 1.0 Largest Size (cm) 4 (1-13) 3.7 (0.3-9) 1.0 Clinical Risk Score 3 67% 64% 0.8 Rectal 1o 23% 30% NS

J Am Coll Surg 2009;208:842

• July 1997 – June 2008
• 230 patients with synchronous

liver metastases

• Staged = 160
• Synchronous = 70
• Unmatched
• No differences
• Demographics
• Disease extent

Staged (n=160) Synchronous (n=70) p Pre-op Chemotherapy 70% 52% 0.001 Lobe Resection 40% 47% 0.2 LAR/APR/Total 35% 40% 1.0 Complications Overall Grade 3 Mortality 55% 21% 2% 56% 19% 2% 1.0 0.5 1.0 OR time 235 min 180 min NS EBL 350 ml 300 ml 0.9 Transfused 45% 50% NS Length of Stay 18 days 10 days 0.001

Synchronous Colorectal Liver Metastases

Martin et al. J Am Coll Surg 2009;208:842

All patients

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Staged (n=64) Synchronous (n=33) p Complications Overall Grade 3 Mortality 60% 32% 2% 50% 15% 0% 0.6 0.5 1.0 OR time 268 min 202 min 0.06 EBL 750 ml 450 ml 0.01 Length of Stay 18 days 12 days 0.001

Synchronous Colorectal Liver Metastases

Martin et al. J Am Coll Surg 2009;208:842

Major hepatic resections only

• Similar results when only major hepatic resections considered

EJSO 2010;36:365

Staged (n=32) Synchronous (n=32) p Age (years) 67 69 ns ASA 2 2 ns Clinical Risk Score 2 2 ns LAR/APR 38% 38% ns Lobe Resection 22% 22% ns Adjuvant/Neoadjuvant Tx 53% 41% ns

• Consecutive synchronous

resections matched to staged procedures

• Matching variables:
• Age
• Gender
• ASA
• Hepatic resection
• Primary resection

Synchronous Colorectal Liver Metastases

EJSO 2010;36:365

Staged (n=32) Synchronous (n=32) p EBL 425 ml 475 ml ns Morbidity 59% 34% 0.7 Mortality

• Length of Stay

20 days 12 days 0.008 Survival Recurrence-Free Overall 5-Year 14 months 42 months 24% 10 months 39 months 21% 0.5 0.8 0.8

• Shorter hospital stay in synchronous group
• No difference in long-term survival

Synchronous Colorectal Liver Metastases

Author Years N Major Hepatectomy Morbidity Mortality Yan et al

• Synch 73

Staged 30 73% 77% 32% 43% 0% 0% Jaeck et al 1982-96 Synch 28 Staged 31 32% 52% 18% 16% 0% 0% Turrini et al 1994-05 Synch 57 Staged 62

• 25%

21% 3.5% 5.0% Stojanovic et al

• Synch 31

Staged 51

• 19%

20% 0% 0% Vassiliou et al 1996-04 Synch 25 Staged 78 28% 29% NS 0% 0% Capussotti et al 1985-04 Synch 70 Staged 57 34% 56% 33% 56% 1% 0% Chua et al 1996-99 Synch 64 Staged 32 16% 41% 53% 41% 0% 0% Tanaka et al 1992-03 Synch 39 Staged 37 13% 54% 28% 16% 0% 0% Martin et al 1984-01 Synch 134 Staged 106 34% 72% 48% 68% 2% 2% Weber et al 1987-00 Synch 35 Staged 62 31% 56% 32% 23% 0% 0%

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Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Analysis

Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS

J Am Coll Surg 2013;216:707-716

• 1,004 Patients with synchronous colorectal liver metastases
• 1982 – 2011
• 4 Institutions
• Treated with curative intent

Resection + ablation of liver disease allowed Extrahepatic metastases allowed if completely resected

• Staged (colorectal first) = 647
• Staged (liver first) = 28
• Simultaneous = 329

Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Analysis

Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS

J Am Coll Surg 2013;216:707-716

Variable Colorectal First (n=647) Simultaneous (n=329) p Age (years) 61 60 ns Primary Colon 74% 72% ns > 2 Liver Metastases 33% 35% ns Major Hepatectomy 39% 24% <0.001 Resection + Ablation 11% 9% ns Chemotherapy (pre or post) 63% 56% <0.001

Surgical Management of Patients with Synchronous Colorectal Liver Metastasis: A Multicenter International Analysis

Skye C Mayo, MD, MPH, Carlo Pulitano, MD, Hugo Marques, MD, Jorge Lamelas, MD, Christopher L Wolfgang, MD, PhD, FACS, Wassila de Saussure, MD, Michael A Choti, MD, MBA, Isabelle Gindrat, MD, Luca Aldrighetti, MD, Eduardo Barrosso, MD, Gilles Mentha, MD, Timothy M Pawlik, MD, MPH, PhD, FACS

Variable Colorectal First (n=647) Simultaneous (n=329) p R0 Resection (liver) 72% 79%

• Severe Complications

11% 11% ns 90-Day Mortality 3.2% 2.7% ns Recurrence 60% 53% ns

J Am Coll Surg 2013;216:707-716

• Staged and simultaneous resections: similar outcomes

Ann Surg Onc 2007;14:3481

• 610 patients over 21 years at 3 centers
• Staged procedures done at same institution: 205 patients
• Simultaneous major hepatic resections: 36 patients

< 1 patient per center per year Combined bias of 3 different institutions

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Synchronous Colorectal Liver Metastases

Staged Synchronous p MAJOR HEPATECTOMY # Length of Stay Severe Morbidity Mortality 51 14 days 18% 36 9 days 36% 8% <0.0001 0.07 0.05 MINOR HEPATECTOMY # Length of Stay Severe Morbidity Mortality 19 14 days 11% 99 8.5 days 14% 1% <0.0001 0.7 0.8

• Authors conclude: combined major hepatectomies should not be done
• Questionable at best
• Based on very small numbers (3 patients)

Accrued over a long time interval

Synchronous Colorectal Liver Metastases

Liver first resection: Why?

• ‘Increasing complexity of care of 1o colorectal cancers’
• Preoperative radiotherapy for rectal cancer

Prevent progression of liver disease Possibility of a complete response

• ‘Liver metastases give rise to widespread systemic disease’
• ‘Option to give systemic therapy as a first step’
• Do these arguments mandate a paradigm shift?

Ann Surg 2012;256:772

Liver 1st (n=58) Colorectal 1st (n=729) p Rectal 1o 57% 23% <0.001 Pre-Colectomy XRT 31% 6% <0.001 Pre-Hepatectomy Chemo Irinotecan + Oxali 21% 4% <0.001 1o Nodal Metastases 41% 72% <0.001 Clinical Risk Score 3 51% 49% 0.2

• Colorectal 1st
• Liver 1st

P = 0.96

• Colorectal 1st
• Liver 1st

P = 0.96

• Liver 1st approach:
• Survival similar to colorectal 1st approach
• Applicable to a very small fraction of all patients

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JAMA Surg 2013;148:385-391

• 4 studies, 121 patients
• Majority of patients with stage IV rectal cancer
• Variable approaches and outcomes
• Represent a small minority of staged resection cases

‘…the title is somewhat misleading…The first treatment in all series was, in fact, chemotherapy…A strong argument could be made that deciding whether the colorectal tumor or the hepatic metastases should be removed first, second or together is not the critical issue. The pivotal factor limiting improvement in patient outcomes appears to be responsiveness to chemotherapy… [Improvement in outcome] will be predicated on the development

• f increasingly effective chemotherapeutic agents, not the

timing of surgical extirpation.’

Klein JAMA Surg 2013;148:392

Summary

• Synchronous resection of hepatic colorectal metastases
• Safe and effective

Shorter overall hospital stay Similar to lower operative morbidity Less utilization of hospital resources Similar long-term results

• Additional potential benefits

Lower cost Shorter time to starting/resuming chemotherapy

• Should be considered for all patients

Summary

• Liver first approach
• Rarely indicated

Rectal cancer with borderline resectable liver disease No evidence of superiority over standard approaches

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Synchronous Colorectal Liver Metastases

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1 Operation is better than 2