Overview Introduction and Historical Perspective Current Surgical - - PowerPoint PPT Presentation

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Carlos U. Corvera M.D. Associate Professor Department of Surgery Chief, Liver, Biliary and Pancreatic Surgery University of California, San Francisco School of Medicine

SURGICAL MANAGEMENT OF METASTATIC COLORECTAL CANCER

UCSF 2013 Postgraduate Course

Overview

• Introduction and Historical Perspective
• Current Surgical Management

– Patient Selection – Define Resectability

• Methods of Extending Resectability

– PVE – Staged Resections – ALPPS – HAIP

• Conclusion

Statistics/ Facts

• ~ 30% to 40% of patients will have liver-only

metastases at time of recurrence

• ~40-50% of patients with advanced CRC

develop recurrence.

• Liver and lung are the most common sites of

metastasis.

• Resection of distant disease can produce long-

term survival and cure in selected patients.

• Unfortunately, only 20-25% are suitable for

resection.

Historical Perspective

Natural History of Metastatic CRC Hepatic Metastases

Wanger and Adson, Ann Surg. 1984: May; 199(5):502-8

Solitary = 21 Solitary = 21 Solitary = 21 Solitary = 21 mos mos mos mos Multiple = 15 Multiple = 15 Multiple = 15 Multiple = 15 mos mos mos mos

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Arch Surg. 1989 Sep;124(9):1021-2. Review

Hunt M.T., Annals of the Royal College of Surgeons of England (1990) vol. 72, 199-2053

Historical Perspective

Improved Mortality Rates

Author N Operative Mortality (%) Scheele ‘91 219 6 Rosen ‘92 280 4 Gayowski ’94 204 Scheele ‘95 469 4 Nordlinger ’95 1568 2 Jamison, ’97 280 4 Fong ’99 1001 3 Belghiti ’00 747 4

Leonard et al. JCO 2005;23:2038-48

Management of Colorectal Metastases

5 yr survival rates remained the same from the 1980‘s- 2003, and only recently, have the 5 year survival rates now been approaching ~50% with modern chemotherapy.

• Stage of primary
• Size of metastasis
• Timing of liver metastases
• Number of metastases
• Preoperative CEA
• Level Bilobar disease
• Perioperative blood transfusion
• Positive Resection margin
• Extrahepatic disease

Factors Associated with Recurrence

Management of Colorectal Metastases

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Fong et al. Ann Surg 1999;230:309-18

Management of Colorectal Metastases

Patient Selection for Hepatectomy

Fong et al. Ann Surg 1999;230:309-18

Management of Colorectal Metastases

Clinical Risk Score*

• 1. Lymph node-positive primary
• 2. Dz-free Interval < 12 months
• 3. Size of liver Tumors > 5 cm
• 4. Number of Liver tumors > one
• 5. Preop CEA >200 ng/mL

*The sum of the positive characteristics is the total score

Fong-Score

Fong et al. Ann Surg 1999;230:309-18

Current Management of Colorectal Metastases

• Severe co-morbidities
• Non – resectable EH Dz
• Synchronous, Multiple

Bilobar Dz

• No tumour – free margin
• NO RESPONE TO CHEMO
• Single (<5cm)
• Metachronous (>1year)
• Favorable primary cancer
• Low CEA

* i.e Low Fong Score

• >4 lesions, especially when synchronous
• Synchronous liver and lung metastases
• Unresectable---->Chemo---->Resectable (~15%)

Who Should Undergo Resection?

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Technical Considerations

• Defining Resectability
• Methods for Improving Resectability
• Portal vein embolization
• Two-staged hepatectomy
• *ALPPS Procedure--Controversial
• Hepatic Arterial Infusion Pump
• High quality cross-sectional imaging
• Selective 3D rendering and CT volumetrics
• FDG PET to rule out more extra hepatic disease

Definition of Resectability

• Ability to remove all gross disease (R0 resection)

and leave an adequate inflow, outflow, and remnant liver volume

• 1. Initially resectable disease by standard

approach

• 2. Initially resectable but requires extended

approach

• staged resections
• preoperative portal vein embolization
• resection plus RFA or Microwave
• ALPPS procedure
• 3. Initially unresectable but likely convertible

with response

• 4. Initially unresectable and unlikely convertible

Categories of Resectability

BORDERLINE

Adam et al. Ann Surg 2004; 240:644-658

Management of Colorectal Metastases

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Adam et al. Ann Surg 2004; 240:644-658

Resection of the Previously Unresectable

Current Management of Colorectal Metastases

Conversion Chemotherapy

• Aim: to achieve potentially

curative surgical resection

• A correlation between

response rate and resection rate is shown.

• But for many patients

resection will not occur therefore consideration must be given to the continuum of care.

• 1. Folprecht, G., et al. Annals of Oncology, 2005. 16(8): p. 1311-1319.

■ studies/retrospective analyses with non-resectable metastases confined to the liver (‘selected patients’, r = 0.96, P=0.002) ▲Studies with non-selected patients with colorectal cancer. Due to the heterogeneity of these studies, the observed correlation is less strong (r = 0.74, P <0.001, solid line). (phase III trials (filled triangles) were separately analyzed (r = 0.67, P=0.024, dashed line).

RESPONSE

Issues with Conversion Chemotherapy

1. Chemotherapy induced hepatotoxicity

– Increases with duration of chemotherapy – Oxaliplatin induced sinusoidal obstruction syndrome >50%1-2 – Irinotecan induced steatohepatitis – Possible association with increased perioperative complications2-5

2. “Disappearing” metastases

• Majority contain viable tumour on resection6-8,
• Found in ~25% of patients treated with preop chemo8
• Approximately 50% are detected during surgery with IOUS8
• True path CR predicted by normalising CEA, inability to detect lesion on MRI7

Minimize treatment duration Surgery as soon as possible8,9

• 1. Rubbia-Brandt , L, et al, Ann Oncol. 2004;15(3):460. 2. Soubrane, O., et al, Ann Surg. 2010;251(3):454 3. Aloia, T., et al., Journal of Clinical Oncology, 2006. 24(31): p.

4983-4990. 4. Vauthey, J.-N., et al.,. Journal of Clinical Oncology, 2006. 24(13): p. 2065-2072. 5. Tamandl, D., et al., Ann Surg Oncol, 2011. 18(2): p. 421-30. 6. Benoist et al, Journal of Clinical Oncology, 2006. 24(24): p. 3939-3945. 7. Auer, R.C., et al., Cancer, 2010. 116(6): p. 1502-1509. 8. vanVledder et al J Gastrointest Surg. 2010 Nov;14(11):1691-700. 9 Nordlinger, B., et al., Ann Oncol, 2009. 20(6): p. 985-92.

Timing of Hepatic Resection

• Traditional Approach: Two-stage approach

1)Colorectal resection (Primary) 2) F/b chemo and delayed hepatic resxn.

Disadvantage = dz progression of CLM b/w the colorectal and hepatic surgery

• Simultaneous resxn of Primary & CLM

– Disadvantage = increased post-op complications when a major hepatic resection of CLM is performed

• Liver First (Reverse) Approach: chemo given

upfront f/b hepatic resxn and finally colorectal cancer resection

Mentha et al. 2006

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Parenchymal-preserving Resections

• Offer greater technical flexibility
• Less extensive resections in patients with limited disease
• Bilateral resections in patients with multiple tumors

Technical Considerations

Metastasis Right hepatic vein Right hepatic vein

Technical Considerations Technical Considerations

Resection of segments VI/VII Posterior Sectorectomy-(Bisegmentectomy)

RHV

Technical Considerations

Central Hepatectomy

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• 1. Conversion Systemic Chemotherpay
• 2. Preoperative Portal Vein Embolization
• 3. Two-Stage Hepatectomy
• 4. “ALPPS” for Associating Liver Partition and

Portal vein Ligation for Staged hepatectomy.

• 5. HAIP

Methods of Improving Resectability

Preoperative Portal Vein Embolization

Methods of Improving Resectability

Tumor Normal Portal Vein Post Embolization

Left Right Left

Required resection

Right

Technical Considerations

Preoperative Portal Vein Embolization PV embolization - regeneration before resection Before Embolization After Embolization

Anticipated liver remnant

Technical Considerations

5/17/2013 8 Gallbladder

PVE- regeneration before resection

Technical Considerations Two-Stage Hepatectomy Methods of Improving Resectability

Jaeck et al. Ann Surg 2004; 240:1037-51

n =25/33

Technical Considerations

Jaeck et al. Ann Surg 2004; 240:1037-51

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Jaeck et al. Ann Surg 2004; 240:1037-51

Technical Considerations

One year after resection

Methods of Improving Resectability

Schnitzbauer et al, 2012

N = 25; 5 centers in Germany 14 patients = metastatic colorectal cancer

“ALPPS” -Associating Liver Partition and Portal vein Ligation for Staged hepatectomy.

Methods of Improving Resectability

de Santibanes and Clavien; 2012

This procedure leads to explosive hypertrophy of ~ 75% of the Left lat. Seg in ~ 9 days.

Kemeny, JCO 23:4888-4896, 2005

Hepatic Arterial Infusion Pump

Methods of Improving Resectability

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Hepatic Arterial Infusion Oxaliplatin Combinations

Kemeny, JCO 23:4888-4896, 2005

Methods of Improving Resectability

Limited to small # of centers; not generally embraced by the Med Oncologists

Summary

• Hepatic resection remains critical to the long-

term outcome of patients with colorectal metastases

• Resectability is an important endpoint.
• Patients should not be consider to be

unresectable unless determined by a competent liver surgeon.

• Those patients determined to be unresectable at

presentation should be followed closely and resectability should be reassessed when significant responses to chemotherapy are

• bserved.
• Progression on Systemic Chemotherapy, in

general should preclude hepatectomy.

CONTACT INFORMATION: Carlos U. Corvera M.D. Associate Professor Department of Surgery Gastrointestinal Surgical Oncology Chief, Liver, Biliary and Pancreatic Surgery University of California, San Francisco School of Medicine Helen Diller Family Comprehensive Cancer Center Email: carlos.corvera@ucsfmedctr.org Phone: Mobile # (415) 317-4602 Direct Line: (415) 502-1690 Clinic Line (referrals) Fax: (415) 353-9931 Tel: (415) 353-9888 Academic Practice: Address: Room U-370 521 Parnassus Avenue San Francisco, CA. 94143 Assistant (Marjorie Galicha) email: Marjorie.Galicha@ucsfmedctr.org tel: (415) 415-476-0762