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!
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