Surgical treatment of colorectal liver metastases

Every patient with colorectal liver metastases should be discussed with a centre with expertise in relation to liver surgery, local treatment techniques of the liver and the (metastatic) colorectal carcinoma.

 

Partial liver resection is preferable above systemic therapy only in patients that meet the criteria for resectability.

 

Liver resections and combination treatments should be performed in centres with:

  • expertise
  • suitable equipment and
  • experience with
    • systemic therapy for colorectal carcinoma
    • local treatment techniques for the liver (surgical and percutaneous treatments)
    • intensive care and
    • anaesthetics in this area

 

Criteria for resectability

With normal liver parenchyma and if there is no neoadjuvant systemic therapy, at least 20 percent of the liver should remain after resection (=residual volume), if extensive resections are being considered.

 

If primary insufficient liver parenchyma would remain after resection, induction systemic therapy and/or portal vein embolisation and/or ‘two-stage’ resections must be considered.

 

The following are not absolute contra-indications; bilobar liver metastases, size of the metastases, synchronicity or no synchronicity, extra-hepatic metastases, stage of the primary tumour, age and value of the serum CEA.

 

Not a contraindication is an expected narrow resection margin. In centres with a lot of expertise, there is the possibility of performing resections directly adjacent to the large vascular and/or bile duct structures with smaller margins. However, a wide margin of 10 mm is recommended because it is difficult to determine the margin beforehand.

 

Simultaneous surgery of the primary tumour and synchronous metastases is not the standard in patients with synchronous liver metastases. The guideline development group is of the opinion that this treatment may be considered after careful selection in centres with vast experience in both colorectal surgery and liver surgery.

 

Surgery should spare as much of the parenchyma as possible.

 

In patients with new liver metastases after earlier liver surgery, re-resection is recommended if the patient meets the criteria for resectability.

 

Radicality is the most important and the desired margin is dependent on the individual patient situation.

 

A limited margin is not a contraindication for (offering) resection.

 

Resection may be considered in patients with limited extrahepatic metastases. This must take place in expertise centres and preferably within a trial context.

 

Age is not an absolute contraindication for partial liver resection.

 

Local therapy for non-resectable liver metastases

Local thermal ablation is an important component in the multidisciplinary treatment of patients with colorectal liver metastases of a relatively limited size (to 3 cm).

 

Local thermal ablation is not an alternative for surgical resection in patients with resectable liver metastases, but may be applied in selected patients in combination with resection in order to make resection possible.

 

Percutaneous local thermal ablation may be applied as local treatment in patients with colorectal liver metastases that are less suitable for surgical resection due to higher age, comorbidity, an unfavourable location of the lesion for resection or a history of extensive abdominal surgery.

 

RFA is currently the local ablation technique of choice.

 

MW ablation may be a good alternative, especially for tumour localisations in which a negative effect of large blood vessels can be expected (heat-sink).

 

With the current RFA and MW techniques, the guideline development group does not see an indication for the use of cryotherapy with colorectal liver metastases.

 

Isolated liver perfusion should only be offered within a trial context.

 

TACE should only be offered within a trial context.

 

Radioembolisation may be considered as salvage therapy in patients with metastases limited to the liver. The value compared to palliative systemic therapy in an earlier phase is not sufficiently known. Treatment should be performed in centres with expertise and preferably within a trial context.

 

The guideline development group is of the opinion that stereotactic radiotherapy may be considered for patients with irresectable colorectal liver metastases in which the location is unfavourable for RFA.

 

Peritonitis carcinomatosa

Selected patients with peritonitis carcinomatosa of colorectal origin are eligible for cytoreductive surgery (CR) and hyperthermic intraperitoneal chemotherapy (HIPEC).

 

The selection criteria for CR and HIPEC are:

  • the disease has spread to at the most 5 of the 7 regions of the abdomen
  • an adequate cytoreduction can be achieved
  • there are no metastases elsewhere (chest and abdominal CT)

It must be determined in advance if a patient meets this criteria.

 

There is no proven added value of PET-CT in preoperative staging for CR and HIPEC.

 

If peritonitis carcinomatosa is found by accident during exploration for the primary tumour and a patient appears to be eligible for CR and HIPEC, it is recommended to leave the primary tumour in situ. Cytoreduction including the primary tumour and HIPEC can then be performed in one intervention, in which implantation does not take place in the resulting surgical tumour bed or the CR with HIPEC is made difficult or postponed by adhesion and complications.

 

Due to the lack of reliable radiological staging of peritonitis carcinomatosa, assessing the indication may be difficult and it is recommended that this takes place in a centre that can also offer CR and HIPEC treatment.

 

Adjuvant chemotherapy may be considered after a HIPEC treatment.

 

Systemic treatment

The choice of systemic therapy in metastatic colorectal carcinoma is largely determined by distinguishing between patients with:

  1. primarily resectable metastasis (aim of treatment: curation)
  2. primarily irresectable but potentially resectable metastases after sufficient response to systemic therapy (aim of treatment: curation)
  3. permanent irresectable metastases (aim of treatment: extending life with maintaining or improving quality of life)

 

Primarily resectable metastases

There is no clear preference for perioperative compared to postoperative chemotherapy.

 

With primarily resectable metastases, perioperative or adjuvant chemotherapy is not considered standard treatment.

 

Certainly with patients who have been treated previously with adjuvant therapy for a stage II/III colon carcinoma, a wait-and-see approach seems justified.

 

Primarily irresectable but potentially resectable metastases

Patients with primarily irresectable but potentially resectable liver metastases should be treated with at least doublet chemotherapy in combination with targeted therapy.

 

In relation to the choice of targeted therapy with RAS wild type tumours, there is no clear preference for an anti-EGFR antibody (cetuximab or panitumumab) above bevacizumab.

 

Neoadjuvant systemic therapy does not increase morbidity of liver surgery unless the duration is limited. Frequent evaluation of the response with imaging (every 8-9 weeks) and multidisciplinary consultation is indicated.

 

Permanent irresectable metastases

For patients with permanent irresectable metastases, chemotherapy plus targeted therapy is standard first-line treatment.

 

Chemotherapy

With patients in good general condition who appear eligible for multiple lines of treatment, and for whom local palliation of symptomatic metastases is not an aim, fluoropyrimidine monotherapy is an alternative to combination chemotherapy. For combination chemotherapy, there is no difference between irinotecan- and oxaliplatin-containing schedules on the basis of effectiveness and incidence of toxicity. The results of triple chemotherapy (fluoropyrimidine, irinotecan, oxaliplatin) are promising. Capecitabine is a good alternative for 5-fluorouracil.

 

Targeted therapy

Standard treatment for patients with a RAS mutated tumour is chemotherapy + bevacizumab. In patients with a RAS wild type tumour who are eligible for multiple lines of treatment, there is a preference for bevacizumab so that anti-EGFT therapy in the second-line in combination with chemotherapy or in a later line as monotherapy can be administered. When only the first-line is considered, there is still insufficient evidence that anti-EGFR is preferable above bevacizumab. Bevacizumab should be administered in combination with chemotherapy. For both bevacizumab and anti-EGFR therapy there is no preferred chemotherapy schedule, with the understanding that there is no data on the combination of anti-EGFR with fluoropyrimidine monotherapy or triple chemotherapy.

 

Continuing bevacizumab after first progression during second-line therapy with an irinotecan- of oxaliplatin-containing schedule, addition of aflibercept to FOLFIRI in the second-line after earlier oxaliplatin-containing chemotherapy with or without bevacizumab, and treatment with regorafenib in late line after failure of all available drugs show a statistically significant survival benefit. Indication for these treatments is made difficult by the limited size of this benefit and the lack of predictive factors.

 

Duration of treatment

The guideline development group is of the opinion that on the basis of current data, continuation of chemotherapy + targeted therapy could be considered until there is progression or unacceptable toxicity.

 

Treatment of elderly patients

The guideline development group is of the opinion that systemic treatment should not be withheld on the basis of elderly age.

Authorization date and validity

Last review : 16-04-2014

Last authorization : 16-04-2014

The validity of this guideline and its associated modules is five years. For various reasons, it may be necessary to edit modules sooner than intended. The National Working Group on Gastrointestinal Cancers therefore annually assesses the content of the guideline and its associated modules. By 2016 it is decided whether a new multidisciplinary working group should be installed to revise the entire guideline.

Initiative and authorization

Initiative : Nederlandse Vereniging voor Radiotherapie en Oncologie

Authorized by:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Klinische Geriatrie
  • Nederlandse Vereniging voor Nucleaire geneeskunde
  • Nederlandse Vereniging voor Pathologie
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging voor Radiotherapie en Oncologie
  • Vereniging Klinische Genetica Nederland

General details

All members were mandated by a scientific, professional or patient association. In the composition of the working group we tried to take national distribution, input from participants from both academic and general hospitals and representatives of various disciplines into account. Patients are also represented by delegation into the working group, as well as a focus group meeting.

Scope and target group

Goal

This guideline and its associated modules are - as much as possible - based on scientific research and / or consensus. It is a document with recommendations to support the daily practice of health care professionals involved in patients with (possible) colon cancer, rectal cancer or colorectal liver or lung metastases. It provides recommendations for diagnosis, treatment, follow-up and organization of care. The guideline and its associated modules are thus seeking to improve the quality of care, to increase transparency of choice for treatment and reduce diversity.

 

Target population

Each year colorectal cancer is identified in approximately 13,000 new patients. Rectal carcinoma occurs in about 1 in 3 patients of this. In the Netherlands, the colorectal cancer in both men and women rank third place in incidence of oncological diseases. The expected number of patients diagnosed with colorectal cancer are increased in 2020 to about 17,000, reflecting a slight increase in incidence (especially in men), population growth and aging.

Colorectal cancer is slightly more common in men than in women and ninety percent of patients 55 years or older. More information about the Dutch population can be found at the Netherlands Cancer Registry: www.cijfersoverkanker.nl

This guideline is applicable to all adult patients with (suspected) a primary colorectal carcinoma and patients with metastatic disease. Particular attention is given to the elderly. A separate guideline is available for adult patients with an increased risk of hereditary colon cancer.

Target Audience

This guideline and its associated modules are intended for all professionals involved in the diagnosis, treatment and rehabilitation of patients with (metastatic) colorectal cancer, such as surgeons, general practitioners, consultants, internists, gastroenterologists, (specialist) nurses, clinical geneticists, paramedics, pathologists, radiologists and radiotherapists. The complete guideline is used to develop a patient education text from the Dutch patients Consumer Federation (NPCF).

 

Samenstelling werkgroep

Name

Function

Hospital

Mandated

Mw. prof. dr. C.A.M. Marijnen chair

Radiotherapist

LUMC Leiden

NVRO

Mw. prof. dr. R.G.H. Beets-Tan

Radiologist

MUMC Maastricht

NVVR

Mw. S. de Bruijn

Specialist nurse

Renier de Graaf hospital Delft

V&VN

Mw. dr. A. Cats

Gastroenterologist

NKI-AVL Amsterdam

NVMDL

Prof. dr. E.F.I. Comans

Nuclear doctor

VUMC Amsterdam

NVNG

Dr. A.R. van Erkel

Intervention radiologist

LUMC Leiden

NVVR

Mw. dr. M.A.M. Frasa

Clinical chemist

Groene Hart hospitalGouda

NVKC

Mw. C. Gielen

Specialist nurse

MUMC Maastricht

V&VN

Dr. E.J.R. de Graaf

Surgeon

IJsselland hospital Capelle a/d IJssel

NVVH

Mw. dr. M. Hamaker

Geriatrician

Diakonessenhuis Utrecht

NVKG

Mw. dr. J.E. van Hooft

Gastroenterologist

AMC Amsterdam

NVMDL

Mw. H.J.A.M.. Kunneman

Researcher

LUMC Leiden

n.v.t.

Mw. dr. M.E. van Leerdam

Gastroenterologist

NKI-AVL Amsterdam

NVMDL

Dr. H. Martijn

Radiotherapist

Catharina-hospital Eindhoven

NVRO

Mw. dr. A.M. Mendez

Romero

Radiotherapist

EMC Cancer Insititute Rotterdam

NVRO

Mw. prof. dr. I.D. Nagtegaal

Pathologist

UMCN St Radboud Nijmegen

NVVP

Dr. L.A. Noorduyn

Pathologist

Lab. Voor Pathologie Dordrecht e.o.

NVVP

Mw. A. Ormeling

Patient

Stomavereniging

NFK

Drs. T.A.M. van Os

Klinisch Geneticus

AMC Amsterdam

VKGN

Dr. F.T.M. Peters

Gastroenterologist

UMCG Groningen

NVMDL

Mw. J. Pon

Patient

NFK/SPKS

NFK

Mw. dr. J.E.A. Portielje

Medical oncologist

Haga hospital Den Haag

Gerionne

Prof. dr. C.J.A. Punt

Medical oncologist

AMC Amsterdam

NIV

Mw. dr. H. Rütten

Radiotherapist

UMCN Radboud Nijmegen

NVRO

Prof. dr. H.J.T. Rutten

Surgeon

Catharina-hospitalEindhoven

NVVH

Prof. dr. J. Stoker

Radiologist

AMC Amsterdam

NVVR

Dr. P.J. Tanis

Surgeon

AMC Amsterdam

NVVH

Dr. J.H. von der Thüsen

Pathologist

MC Haaglanden Den Haag

NVVP

Prof. dr. H.M.W. Verheul

Medical oncologist

VUMC Amsterdam

NIV

Prof. dr. C. Verhoef

Surgeon

EMC Cancer Insititute Rotterdam

NVVH

Dr. Tj. Wiersma

General practitioner

NHG

NHG

 

 

Name

Function

Location

Mw. drs. A.Y. Steutel

process manager

Utrecht

Drs. T. van Vegchel

process manager

Amsterdam

Mw. S. Janssen-van Dijk

secretary

Rotterdam

M.P.  van den Berg

Researcher

Bilthoven

P.F. van Gils

Researcher

Bilthoven

Mw. J. Robays

Methodologist

Brussels

Mw. drs. Y Smit

Methodologist

Germany

Mw. A. Suijkerbuijk

Researcher

Bilthoven

Mw. dr. L. Veerbeek

Methodologist

Groningen

Mw. dr. L. Verheye

Methodologist

Brussels

Mw. dr. G.A. de Wit

Researcher

Bilthoven

 

Patient involvement

Two patient experts have been part of the guideline development group. One on behalf of the Dutch Ostomy Association and on behalf of SPKS/NFK. Based on a focus group meeting experiences of patients regarding care were collected. The guideline also has been used to develop a patient education text for the Dutch patients Consumer Federation (NPCF).

Method of development

Evidence based

Implementation

Promoting the use of recommendations begins with a broad (digital) distribution of the guideline, using direct mailing and an article published in the Dutch Journal of Oncology. In other journals or training sessions, for example, the guideline is brought to the attention. An implementation plan for this guideline contains the key recommendations and an overview of barriers and facilitators for implementation.

Methods and proces

The working group met in July 2012 for the first time. Based on an initial list of problems by working group members a survey among professionals involved in patients with colorectal carcinoma was held. Through this survey, sixty professionals supplied and prioritized possible subjects for revision. Also, a focus group meeting was held, collection patients' experiences. The eleven most relevant questions were answered, and translated into English. Also, alle recommendations were translated into English.

 

Each clinical question was andwered by a subgroup within the development group. External methodologists provided the literature search, review, critical assessment, evidence tables and a draft literature review. Workgroup members suggested other considerations and recommendations.

Responsibility

The Comprehensive Cancer Organisation the Netherlands (IKNL) promotes that people with cancer and their families have access to a consistent and qualitatively adequate care as close to home as possible. IKNL was established to improve treatment, care and clinical research in oncology. It also has a role in setting up and supporting networks for palliative care. IKNL supports multidisciplinary guideline development for oncology and palliative care and facilitates the maintenance, management, implementation and evaluation of these guidelines.

AGREE was used to check the methodological quality of the guideline.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.