Question

What is the added value of local treatment, either in combination or not in combination with neoadjuvant (chemo)radiotherapy, compared to conventional surgery in patients with a stage I-IV rectal carcinoma in relation to local follow-up, quality of life and survival?

Recommendation

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.

Conclusions

Stage I patients

For patients with T1 rectal carcinoma:

  • there is evidence of very low quality that no local recurrence occurs after 5 years, and metastasis develop in 11% of patients

 

General quality of evidence=very low

 

Stage II patients

For patients with a T2N0M0 rectal carcinoma, treatment with neoadjuvant chemoradiation and transanal endoscopic microsurgery or laparoscopic resection:

  • there is evidence of low quality that there is an equal chance of developing a local recurrence and metastases
  • there is evidence of moderate quality that the 10-year disease-specific and general survival are equal
  • there is evidence of moderate quality that less patients will have a permanent stoma after microsurgery

 

General quality of evidence=moderate


Stage III patients

For patients with a clinical T3 rectal tumour, treated with neoadjuvant (chemo)radiation, and not suitable for radical resection due to comorbidity or with a complete clinical response to neoadjuvant therapy:

  • there is evidence of very low quality that local recurrences after 10 years are as common after local excision compared to radical resection
  • there is evidence of very low quality that the disease-specific survival and general survival after local excision are the same as with radical resection
  • there is evidence of very low quality that after six to 178 months, 0-27% local recurrences develop after a local resection
  • there is evidence of very low quality that after approximately 5 years, 74-100% are still alive after local resection, and that 71-91% are still alive without (locoregional) recurrence

 

General quality of evidence=very low

Literature summary

Stage I patients

An observational study followed 18 patients after neoadjuvant radiotherapy and local resection (Luglio 2011 1). Only an abstract was reported for this study and it was not completely clear if in fact all patients underwent neoadjuvant radiotherapy.

 

Quality of the evidence

The quality of the evidence started at 'low’ because it concerned observational studies. The value was lowered due to the small number of patients and events, so that the results are fragile. The resulting quality of evidence was therefore very low.

 

Desired effects

Effect on local follow-up (crucial outcome)

After five years, no local recurrence was seen in the 18 patients after neoadjuvant radiotherapy and local excision (Luglio 2011). A metastasis was found in two patients (11%).

 

Effect on survival (crucial outcome)

An effect on survival was not described in the selected studies.

 

Quality of life (crucial outcome)

An effect on the quality of life was not described separately for T1 patients in the studies selected.

 

Undesired effects

Undesired effects were not described in the studies selected.

 

Stage II patients

A trial randomised 100 T2N0M0 patients between transanal endoscopic microsurgery and laparoscopic resection (Lezoche 2012 2). Both groups received neoadjuvant chemoradiation for surgery. A randomised trial was available, and a search was therefore not made for observational studies.

 

Quality of the evidence

The value was lowered for the outcome recurrence because patients and assessors were not blinded, in which it was assumed that this would not present a risk of bias for the outcome survival or stoma. The value was lowered for all outcomes because of inaccuracy in relation to the small number of events.

 

Desired effects

Effect on local follow-up (crucial outcome)

After 10 years of follow-up, there were an even number of recurrences and metastases in both groups (12%, 95%BI 6-25% versus 10%, 95%BI 4-22%, p=0.69) (Lezoche 2012). In a regression analysis, the type of surgery was strongly related to the risk of recurrence and metastases (RR 14.24, 95%CI: 1.36-149.16; p=0.03). This can probably be explained by the fact that recurrences & metastases developed earlier in the microsurgery group (five of the six events in the first year) compared to the laparoscopic group (none of the five events in the first year).

 

Effect on survival (crucial outcome)

After 10 years, the disease-specific survival was equally high after microsurgery (89%, 95%BI 70-96%), compared to laparoscopic resection (94%, 95%BI 82-98%) (p=0.69) (Lezoche 2012). The same applied to general survival (72%, 95%BI: 51-86%) versus 80% (95%BI: 62-90%) (p=0.61).

 

Quality of life (crucial outcome)

None of the patients after microsurgery had a permanent stoma, compared to 12 patients after laparoscopic resection (p<0.01) (Lezoche 2012).

 

Undesired effects

Postoperative death did not occur in either of the two treatment groups (Lezoche 2012). Changes in the surgical treatment plan and/or conversions to open surgery were more common in the laparoscopic resection group (0 versus 6, p<0.001). Side effects (6 versus 7, p=0.77) and serious side effects (1 versus 3, p=0.25) were equally common in both groups. 

Stage III patients
Nine studies described the effect of local excision in patients with a stage III rectal carcinoma (Callender 2010 3; Guerrieri 2008 4; Nair 2008 5; Meadows 2006 6; Mohiuddin 1994 7; Kennelly 2012 8; Schell 2002 9; Tennyson 2012 10; Yeo 2010 11). One study was a comparative cohort study (Callender 2010), and compared 47 T3N0-1 patients who underwent local excision with 473 patients who underwent TME (Callender 2010). All patients received neoadjuvant chemoradiation. Patients underwent a local excision due to comorbidity (n=12), refusing TME (n=15) or a complete clinical response to neoadjuvant therapy with a strong preference for local excision (15) or other/not documented reasons (n=5). Patients who underwent local excision were older, had a smaller tumour and less often macroscopic residual tumour after chemoradiation, compared to patients who underwent TME. The other eight studies followed in total 172 T3N0-1 patients after neoadjuvant (chemo)radiation and local excision (Guerrieri 2008 4; Nair 2008 5; Meadows 2006 6; Mohiuddin 1994 7; Kennelly 2012 8; Schell 2002 9; Tennyson 2012 10; Yeo 2010 11). Patients underwent local excision because they were not eligible for radical resection due to comorbidity or because they refused radical resection (Guerrieri 2008; Kennelly 2012; Mohiuddin 1994; Nair 2008; Tennyson 2012; Yeo 2010). A small proportion of the patients made an informed consent choice for local excision after (a) the tumour was ≤T2 and <3 cm after radiation (n=15) (Mohiuddin 1994); or (b) after the tumour was T0-1 and <2 cm after chemoradiation (n=11) (Schell 2002). The study by Kennelly et al, excluded patients who had no or barely a clinical response to neoadjuvant chemoradiation.

 

Quality of the evidence

The quality of the evidence started at 'low’ because it concerned observational studies. The value was lowered due to the small number of patients and events in one group, so that the results are fragile. The resulting quality of evidence was therefore very low.

 

Desired effects

Effect on local follow-up (crucial outcome)

In the study by Callender et al., 10-year local recurrences were as common in the local excision group compared with the TME group (10.6 versus 7.6%; p=0.52) (Callender 2010). In seven cohort studies that followed patients after local excision, local recurrences developed in 0-27% of patients after a follow-up of 4 to 153 months (Table 1 Number and percentages local recurrences in T3N0-1M0 patients after neoadjuvant (chemo)radiation and local excision ). The two small studies that only included patients with a good response to chemoradiation found no local recurrences during follow-up (Kennelly 2012; Schell 2002).

 

Table 1 Number and percentages local recurrences in T3N0-1M0 patients after neoadjuvant (chemo)radiation and local excision

Study

Follow-up

Patient characteristics

Number of patients

Number of local   recurrences

%  

Guerrieri 2008

Range: 12-1 and <3 cm 78 months 1

Too much comorbidty for radical   resection, or refused

61

3

5%

Kennelly 2012 2

Median: 24 months (range: 9-42)

Patients with no/barely a response   to chemoradiation were excluded

10

0

0%

Mohiuddin 1994

Median 40 months (range: 12-96) 1

Too much comorbidty for radical   resection or ≤T2 after neoadjuvant radiotherapy

30

3

10%

Nair 2008

Median 64 months (range: 6-153) 1

Too much comorbidty for radical   resection, or refused

22

2

10%

Schell 2002 3

Median 48 months (range: 18-105)

Elective, after significant   response to neoadjuvant therapy

11

0

0%

Tennyson 2012

Median 5.9 year (range: 0.3-11.1 jaar)

Too much comorbidty for radical   resection, or refused

11

3

27%

Yeo 2010

Median 59 months (range: 24-85)

Refused radical resection

11

1

9%

  1. Only available for T2+T3 patients
  2. Patients with little or no clinical response to neoadjuvant chemoradiation were excluded
  3. Included elective patients with a significant clinical response to neoadjuvant chemoradiation

 

Effect on survival (crucial outcome)

In the study by Callender et al., the 10-year disease-free survival did not differ between the local excision group and the TME group (data reported in a figure, p=0.59) (Callender 2010). The same applied to the 10-year disease-specific survival (data reported in a figure, p=0.64) and the 10-year general survival (data reported in a figure, p=0.81). In the six studies that followed T3 patients after local excision, survival after approximately five years was between 74% and 90%; the disease-free survival was between 71% and 77% (Table 2 (Disease-free) survival in T3N0-1M0 patients after neoadjuvant (chemo)radiation and local excision ).

 

Table 2 (Disease-free) survival in T3N0-1M0 patients after neoadjuvant (chemo)radiation and local excision

Study

Follow-up

Patient characteristics

Number of patients

Survival

Survival without   (loco-regional) recurrence

Guerrieri 2008

Range: 12-178 months 1

61

Too much comorbidty for radical   resection, or refused

-

77%

Meadows 2006

Median 27 months (range: 2-123) 1

16

Not reported

-

71%

Mohiuddin 1994

5 years

15

Too much comorbidty for radical   resection

74%

-

Mohiuddin 1994

5 years

15

≤T2 after neoadjuvant radiotherapy

88%

-

Nair 2008

Median 64 months (range: 6-153) 1

22

Too much comorbidty for radical   resection, or refused

90%

-

Schell 2002

Median 48 months (range: 18-105)

11

Elective, after significant   response to neoadjuvant therapy

100%

91%

Yeo 2010

Median 59 months (range: 24-85)

11

Refused radical resection

91%

82%

  1. Only available for T2+T3 patients

 

Quality of life (crucial outcome)

Aspects of the quality of life were not described for T3 patients in the studies selected.

 

Undesired effects

Undesired effects were not described in a comparison with patients who underwent radical resection.

 

 

Considerations

No considerations are described.

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).

 

Members of the guideline panel

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.