How to deal with synchronousprimary and liver metastases

Dimitri Dorcaratto MD, PhD, FEBSDepartment of Surgery. Liver-Biliary and Pancreatic UnitHospital Clínico. University of Valencia

DISCLOSURE

Nothing to disclose

Definition

• Diagnosed at the same time as the CRC

Pre-operative stagingIntraoperative finding (urgent surgery CRC)

• 3-6 months after resection

Adam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

Definition

• Diagnosed at the same time as the CRC

Pre-operative stagingIntraoperative finding (urgent surgery CRC)

• 3-6 months after resection

20-30% of patients with CRC

Adam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

• Simultaneous: Liver metastases and the primary tumor are resected in the same operation (Vogt, 1991)

• Sequential bowel-first: First resection of the CRC and then the liver metastases.With or without Chemo during the interval

• Sequential liver first (reverse approach):Resection first of all liver metastases and later the CRC (Mentha G, 2006)

Definition

Advantages Disadvantages

Avoid two operations Long surgical time

Shorter length hospital stay Specialised surgeons required

Lower costs Bacterial contamination

Resection of all disease, lower risk of dissemination

Safety of bowel anastomosis

Chemo starts early and in betteroncological conditions

The biological behaviour of the tumor is not observed

Simultaneous

Simultaneous

Advantages Disadvantages

Avoid two operations Long surgical time

Shorter length hospital stay Specialised surgeons required

Lower costs Bacterial contamination

Resection of all disease, lower risk of dissemination

Safety of bowel anastomosis

Chemo starts early and in betteroncological conditions

The biological behaviour of the tumor is not observed

Advantages DisadvantagesLess aggressive surgery Two surgical operations

Better management of complexsurgeries

Longer length of hospital stay

Evaluation of tumor behaviour If complications, delays liver surgery orChemo

Increase in global morbidity

Disease progression during postoperativeperiod

Higher costs

Sequential bowel-first

Advantages DisadvantagesLess aggressive surgery Two surgical operations

Better management of complexsurgeries

Longer length of hospital stay

Evaluation of tumor behaviour If complications, delays liver surgery orchemo

Increase in global morbidity

Disease progression during postoperativeperiod

Higher costs

Sequential bowel-first

.Rationale1 : the lesion that kills the patient is the metastasis

Rationale 2: metastases usually determine resectability

Rationale 3: progression of the CRLM during treatment of the primary tumour

Sequential liver-first

Mentha G et al. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006 Jul;93(7):872-8.

Advantages Disadvantages

To treat what determines resectabilityComplications of primary CRC requiringurgent or palliative surgery (5-11 %)

Avoids progression of livermetastases

CRC progression (rare)

Allows the most appropriatte timing of administration of pelvis Chemo-RDT

Small size liver M1 disappearance

Chemo treatment of liver metastases and the primary CRC

Two surgical operations

Increase OS if conversion of M1 to resectables

Sequential liver-first

Sequential liver-first

Advantages Disadvantages

To treat what determines resectability Complications of primary CRC requiringurgent or palliative surgery (5-11%)

Avoids progression of liver metastases CRC progression (rare)

Allows the most appropriatte timing of administration of pelvis Chemo-RDT

Small size liver M1 disappearance

Chemo treatment of liver metastases and the primary CRC

Two surgical operations

Increase OS if conversion of M1 to resectables

Summary Scientific Evidence

• No randomized (RCT) studies

• Important selection biases

• Sequential in patientes with greater liver disease

• Increased evidence on simultaneous resections

Scientific EvidenceSIMULTANEOUS vs Sequential BOWEL FIRST vs Sequential LIVER FIRST

Brouquet A, Mortenson MM, Vauthey J-N et al. Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy?J Am Coll Surg 2010; 210: 934-941

Scientific Evidence

Simultaneous resection

N=922

N=922

Simultaneous resection

N=922

Patients selection is crucial

Simultaneous resection

135 HospitalsNew York State2005-14

Abelson JS et al. J Gastrointest Surg 2017

Simultaneous resection

135 HospitalsNew York State2005-14

Abelson JS et al. J Gastrointest Surg 2017

Simultaneous resection

Abelson JS et al. J Gastrointest Surg 2017

Simultaneous resection

Abelson JS et al. J Gastrointest Surg 2017

Simultaneous resection

5 years OS:Simultaneous: 38,5%Staged: 38,9%

N=429Simultaneous=320Staged=109

Simultaneous resection

5 years DFS:Simultaneous: 24,3%Staged: 25,3%

N=429Simultaneous=320Staged=109

Simultaneous resection

Gavriilidis et al. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis. HBP 2018.

30 studies5300 patients

Simultaneous resection

Gavriilidis et al. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis. HBP 2018.

30 studies5300 patients Overall survival

Simultaneous resection

Sturesson Ch et al. Liver-first strategy for synchronous colorectal liver metastases-an intention-to treat analysis. HBP 2017; 19: 52-58

Liver first strategy

Classical30 %

Do not complete the plannedtreatment

(two surgeries)

Liver-first35 %

Do not complete the plannedtreatment

(two surgeries)

Sturesson Ch et al. Liver-first strategy for synchronous colorectal liver metastases-an intention-to treat analysis. HBP 2017; 19: 52-58

Liver first strategy

Liver first strategy

54,0%

49,0%

Liver first strategy

Vallance AE et al. The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis 2018

Synchronous primary CRC and liver metastases

Trends in surgical strategy

Scientific EvidenceSIMULTANEOUS vs Sequential BOWEL FIRST vs Sequential LIVER FIRST

• No differences in survival... ... in selected cases

• No differences in complications… … in selectedcases

• Simultaneous: shorter length of hospital stay andlower costs

• Liver first approach: severe liver disease and asymptomatic primary tumour

Summary Scientific Evidence

Indications and clinical recommendations

Primary tumor• Symptoms• Rectal vs colonic• Extent of the surgery

Liver mets• Resectability• Extent of the surgery/disease• Extrahepatic disease

• Fit for surgery?Patient

Indications and clinical recommendations

Primary tumor• No symptoms• Colon• Easy

Liver mets• No extrahepatic disease• Easy• Limited disease

ChemotherapyCombined resection

Adam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

1

Indications and clinical recommendations

Primary tumor• No symptoms• RECTAL• Easy

Liver mets• No extrahepatic disease• Easy• Limited disease

Chemotherapy+RT

Combined resection

Adam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

2

Indications and clinical recommendations

Primary tumor• No symptoms• Colon• Easy

Liver mets• No extrahepatic disease• Extensive disease• Bilateral disease

ChemotherapyLiver first surgery

AAdam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

3

Indications and clinical recommendations

Primary tumor• No symptoms• Colon• Easy

Liver mets• No extrahepatic disease• Extensive disease• Bilateral disease

ChemotherapyCombined

BSecond stage liver

PORTALEmbolization

3

Indications and clinical recommendations

Primary tumor• No symptoms• Colon• Easy

Liver mets• No extrahepatic disease• Extensive disease• Bilateral disease

ChemotherapyCombined

BSecond stage liver

PORTALEmbolization

3

Indications and clinical recommendations

Primary tumor• No symptoms• Colon• Easy

Liver mets• No extrahepatic disease• Extensive disease• Bilateral disease

ChemotherapyCombined

BSecond stage liver

PORTALEmbolization

3

Indications and clinical recommendations

Primary tumor• SYMPTOMS• Colon• Easy

Liver mets• No extrahepatic disease• Easy• Limited disease

Primary surgeryChemotherapy

Liver surgeryAdam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

4

Indications and clinical recommendations

Primary tumor• SYMPTOMS• Colon• Easy

Liver mets• No extrahepatic disease• Extensive disease• Bilateral disease

Primary surgeryChemotherapy

Liver surgeryAdam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

5

SIMULTANEOUS Surgery

Indications and clinical recommendations

• Patients fit for surgery

• “Easy” hepatic resection

• Uncomplicated primary tumor

• Specialized surgeons

Adam R et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary internationalconsensus. Cancer Treat Review 2015.

SEQUENTIAL COLON FIRST Surgery

Indications and clinical recommendations

• Symptomatic CRC

• Patient not fit for simultaneous

• Surgeon not an expert in liver surgery

• Doubtful resectability of CCR

• Complex surgery of the CRC and the M1

SEQUENTIAL LIVER FIRST Surgery

Indications and clinical recommendations

• Asymptomatic primary tumor

• Unresectable or borderline resectable liver M1

• Risk of M1 progression during treatment of the primary

Management of the disappearing metastases

Incidence: 5-38 %

Try to avoid this problem• Early involvement of surgeon: Multidisciplinary board

• Limit the duration of chemo

• Coils to mark M1 if risk of disapearing

Adams RB et al. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HBP 2013; 15: 91-103Lucidi V et al. Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases. World J Gastroenterol2016; 22: 3937-3944

1. M Karoui, et al. Ann Surg vol 243, Number 1; January 20062. Folprecht G. Eur J Cancer. 2011 Sep;47 Suppl 3:S52-60.

Incidence: 5-38 %

Try to avoid this problem• Early involvement of surgeon: Multidisciplinary board

• Limit the duration of chemo

• Coils to mark M1 if risk of disapearing

Management of the disappearing metastases

Surgical resection should include all original sites of M1…when feasible

Complete radiological response IS NOT EQUIVALENT to complete pathological response

Watch-and-wait strategy can be a reasonable alternative

Adams RB et al. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HBP 2013; 15: 91-103Lucidi V et al. Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases. World J Gastroenterol2016; 22: 3937-3944

Management of the disappearing metastases

Recurrence in 30-70%

Summary

• Multidisciplinary treatmnent strategies

• Selection of patients

• Planification for an appropriate timing

• Complex surgical procedures requiring surgical expertise

Synchronous primaryand liver metastases

Painting: Sandra Villa LagoPhotograph: David Gimeno VesesSchool of Medicine. Universitat de Valencia

Thank you!