Neoadjuvant radiotherapy

All patients with a rectal carcinoma should be discussed prior to surgery in a multidisciplinary oncological consultation.

 

For low-risk resectable rectal carcinoma (cT1-3N0, extramural invasion to ≤5 mm, distance to MRF >1 mm), surgery according to the TME principle without neoadjuvant radiotherapy should be considered the standard.

 

For high risk and locally advanced rectal carcinoma (cT3 with a distance to the MRF ≤1 mm or cT4, and/or high chance of 4 or more positive lymph nodes within the mesorectum or positive lymph nodes outside the mesorectum on the basis of MRI), neoadjuvant chemoradiotherapy followed by surgery should be considered the standard.

As chemoradiotherapy, a radiotherapy schedule with a dose of 45-50 Gy (in fractions of 1.8-2 Gy) with oral chemotherapy (capecitabine 825-1.000 mg/m2 twice per day for a duration of 5-7 days per week throughout radiotherapy) should be considered.

 

For intermediate risk resectable rectal carcinoma (cT1-3N1 or cT3N0 with extramural invasion >5 mm, distance to the MRF >1 mm), short-lasting preoperative irradiation (25 Gy in fractions of 5 Gy) prior to TME surgery should be considered.

 

Given the uncertainty of the clinical N-stage, it is recommended to discuss the benefits and disadvantages of neoadjuvant radiotherapy expressly with the patient.

 

Possible postoperative (chemo)radiotherapy after TME surgery without pre-treatment should not be considered.

 

As alternative for chemoradiotherapy at, for example, a high age, or with comorbidity, a short schedule (25 Gy in fractions of 5 Gy) may be considered, with delayed surgery (interval of at least 8 weeks).

 

On the basis of the available data, no clear recommendation can be given in relation to the time interval between the end of chemoradiotherapy and surgery. The usual interval is 8-12 weeks.

 

The distance to the MRF of the primary rectal carcinoma is the leading factor in ascertaining the indication for neoadjuvant therapy and not the distance of a possible pathological node to the MRF.

 

Table 1 Schematic display of the indication for neoadjuvant treatment

Tumour stage (MRI staged)

Neoadjuvant   treatment

cT1-2N0 or cT3N0 ≤5 mm extramural invasion;

distance to the MRF >1 mm

None

cT1-3N1 or cT3N0 >5 mm extramural invasion; distance to the MRF >1 mm

5x5 Gy pre-operative radiotherapy

cT4 of cT3 with distance to the MRF ≤1 mm

and/or

cN2 / extramesorectal pathological nodes (each N)

Chemoradiotherapy

 

Total Mesorectal Excision (TME)

It is recommended to perform radical surgery for resectable rectal carcinoma according to the TME principles.

 

The quality of the TME sample is preferably classified and documented with colour photos in at least two orientations:

  • good quality in the case of an intact visceral covering of the mesorectum
  • moderate quality if there are rips in the surgical margin, and
  • poor quality if the muscularis propria of the rectum is visible

 

Possible perforation of the intestinal wall should be reported by the surgeon as well as the pathologist.

 

With distally located rectum carcinomas, a low anterior resection, possibly even intersphincteric resection, may be considered if a tumour-free distal margin with a CRM of >1 can be achieved.

 

In the case of proximal rectal carcinomas, resection of the distal mesorectum may be omitted if adhering to a distal margin of 5 cm (partial mesorectal excision or PME).

 

An AbdominoPerineal Resection (APR), Low Anterior Resection (LAR) or intersphincteric resection for treatment of rectal carcinoma should be based on:

  • a preoperative analysis of the height of the carcinoma
  • the stage (with distal rectal carcinomas)
  • the relationship with surrounding structures such as sphincter complex and the m. levator ani
  • the comorbidity
  • the age of the patient
  • the preoperative sphincter function
  • the distal boundary of the irradiation field (sphincter spared or not spared)
  • the preference of the patient

 

With an APR for a distal rectal carcinoma, the TME dissection should not be continued through to the pelvic floor, but an extralevator technique should be applied in which the pelvic floor muscles are included in the resection so that an extra margin around the tapered mesorectum is achieved.

 

Rectum-sparing treatment

Possible rectum-sparing treatment of a rectal carcinoma should only be considered after complete staging in a multidisciplinary oncological consultation, with the point of departure that this is an alternative treatment for radical TME surgery with less evidence for long-term oncological safety. In doing so, it is a condition that there is expertise.

 

Local excision of a rectal tumour should be performed by means of an endoscopic technique (transanal endoscopic microsurgery (TEM) or single port transanal endoscopic surgery (SPTS)). These techniques are preferable above a conventional transanal excision (TAE).

 

To determine tumour-free margins after local excision of a rectal tumour, carefully standardised pathological analysis should be performed.

 

If there is a clinically evaluated low-risk rectal carcinoma (diameter smaller than 3-4 cm, well to moderately differentiated, no lymphangioinvasion), local excision without neoadjuvant therapy may be considered.

 

If after local excision of a rectal abnormality an invasive carcinoma is found, additional radical surgery should be performed with a high risk T1 (poorly differentiated and/or lymphangioinvasion and/or tumour-free margin <1 mm / inconclusive resection margins) or T2 stage. If there is doubt about the radicality, radiotherapy prior to the completion TME surgery may be considered.

 

Neoadjuvant (chemo)radiotherapy followed by local excision with a clinically high-risk T1N0 (poorly differentiated, lymphangioinvasion) or T2-3N0 rectal carcinoma should only be considered if standard treatment by the patient is not tolerated (age, comorbidity) or is refused, or in a trial context.

 

If there is a complete clinical response after (chemo)radiotherapy, a local excision of the scar should be considered in order to determine the pathological response. If a ypT0-1 stage is found, follow-up may be decided. With a ypT2-3 stage, additional radical surgery with an interval of 6-8 weeks is recommended.

 

After (chemo)radiotherapy with a complete clinical response (therefore without local excision), a wait and see approach should not be applied outside of a trial context.

 

During follow-up after local excision of a rectal carcinoma, an endoscopic inspection of the scar and pelvic MRI with intervals of 3 to 6 months should be performed in the first 2 to 3 years, alongside the standard follow-up focused on distant metastases and surveillance colonoscopy.

 

A recommendation about possible endorectal ultrasound after local excision cannot be made on the basis of the available literature.

 

Centralisation of T4 and local recurrence

T4- and local recurrence rectal carcinomas should be treated in a centre with sufficient expertise in this area.

 

Part of the pre-treatment can take place in their own region in close consultation with the centre.

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).

 

Member of workgroup

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.