Question

Does additional (segmental) colon resection yield better outcomes (PFS, OS< QOL) than watchful waiting in patients who are diagnosed with Tis/T1 colon carcinoma and who have undergone endoscopic polypectomy?

Recommendation

Polypectomy alone suffices to radical resection (resection margin> 1 mm) of a well or moderately differentiated colon carcinoma without T1 (lymph) angiogenic invasion. In all other cases (resection margin ≤1 mm and / or poorly differentiated, and / or (lymph) angio-invasion) additional surgical resection should be considered.

 

If the resection margin in a malignant sessile polyp cannot be determined, or whether the polyp is removed using piecemeal resection, a surgical resection should be considered.

 

At clinically suspected malignant polyps - for the benefit of any additional resection if indicated - the polypectomy site should be distally marked with a 2 to 3 markers. Markers can also be used for determining local recurrence.

 

In additional surgery a formal oncological colon resection should be performed with adequate mesocolic lymphadenectomy.

 

Additional surgical resection after endoscopic removal of a malignant polyp should always be a weighted decision because of the relatively high "number needed to treat," where patients should be fully informed about the possible cancer benefit on the one hand and the risk of complications on the other.

 

Endoscopic removal of a malignant polyp should be staged and followed-up in accordance with the recommendations of T1 colorectal carcinoma. Endoscopic follow-up of scar polypectomy is recommended after three and then after six months. After that, follow-up in accordance with the Dutch guideline Colonoscopy Surveillance is recommended.

 

Conclusions

There is no evidence to compare the effect of polypectomy followed by surveillance with polypectomy followed by (segmental) colon resection in patients who were diagnosed with Tis/T1 colorectal cancer after endoscopic polypectomy, in terms of overall survival, progression-free survival or quality of life.

 

Literature summary

Four evidence-based guidelines that included treatment of early-stage colon cancer were identified in the literature. Only two of them formulated recommendations on the preferred treatment for Tis/T1 cancer found colorectal polyps. Recommendations are summarized in Table 1. In the NICE Clinical Guideline on colorectal Cancer(1), one of the research questions resembled research question 3 very closely: " For patients diagnosed with stage I colorectal cancer, including/or polyp cancer, what are the prognostic factors for determining the most effective curative treatment?". Extensive search strategy for RCTs and observational studies was applied in Medline, Premedline, EMBASE, Cochrane Library, Cinahl, BNI, Psychinfo, Web of Science (SCI & SSCI) and ISI Proceedings and Biomed Central. The authors concluded that there was no evidence with which to answer this question as much of the literature concentrates on identifying the unfavourable prognostic features rather than focusing on the long term outcomes related to such features or which type of treatment is best for patients with specific unfavourable characteristics. The recommendations cited in the Australian NHMRC Guideline(2) concentrate on the clinical (tumour site and general health status), histopathological (tumour-free margin, differentiation grade, lymphatic and/or venous invasion and completeness of removal) and patient-related (age and wishes) prognostic factors for patients with malignant polyps. The recommendations are based on one systematic review of retrospective case series(3), 1 RCT(4) (comparing laparoscopy-assisted colectomy versus laparotomy) 3 narrative reviews and 5 case series. The systematic review (based on 31 English papers published between 1980 and 2003 and obtained solely through a Medline search) concluded that a positive resection margin is largely predictive of residual local disease, the presence of poorly differentiated carcinoma is mainly associated with a higher cancer-related mortality and vascular invasion with a higher risk of lymph node metastasis(3).

 

An additional search was performed for RCT's and observational studies published in 2011-2012 (i.e. after the search date of the NICE Clinical Guideline on colorectal Cancer(1)). No study design filters were employed. The additional search did not yield any (randomized or non-randomized) comparative study that reported the primary outcomes of interest (Overall survival, PFS, QoL) for polypectomy followed by surveillance versus polypectomy followed by surgery.

 

Considerations

There are some observational studies that suggest that polypectomy followed by surveillance maybe safe for low-risk Tis/T1 CRC but not in high risk cancer.

The results of one review of observational studies and five observational studies (all with methodological limitations) are listed below. All studies are considered of very low quality as no appropriate eligibility criteria for the different treatment groups were applied, confounding was not appropriately controlled and there were no data on the completeness of follow-up.

In 2012 Di Gregorio and co-workers(9) performed a review on the available literature on the outcome of low- and high-risk malignant colorectal polyps. No quality assessment of the included observational studies was performed. High risk polyps were defined by the presence of at least one of the following histological features: positive resection margin, poorly differentiated adenocarcinoma, lymphatic/vascular invasion or tumour budding. If none of those features were present, polyps were classified as low risk. Overall, there were 345 patients with a low risk polyp reported, of whom 53 underwent surgery after polypectomy. In one of the 53 surgical specimens, residual disease was reported. One of the 345 low risk cancer patients died due to cancer. There were in total 471 patients with a high risk polyp included, 335 of them underwent surgery. In 49 of the 335 (14.6%) surgical specimens, residual cancer was seen; 23/471 (4.9%) patients died due to cancer. Results for the separate risk factors (present vs. absent) are summarized in Table 7. These results should be interpreted with great caution as it is not clear which patients underwent surgery and there is no correction for the other risk factors.

 

Benizri et al.(10) summarized a retrospective case series of 64 patients with T1 CRC in whom resection (either by laparotomy or laparoscopy) and regional lymphadenectomy was performed after analysis of the polypectomy specimen had revealed at least one of the following adverse criteria: inadequate excision with cancer free distance of the resection margin ≤ 1 mm, lymphovascular invasion, poorly differentiated carcinoma (grade III), submucosal SM 2-3 involvement, tumour budding, sessile morphology or piecemeal resection (see Table 8). The rate of residual adenocarcinoma and/or lymph node metastasis was 7/64 (11%). Post-operative complications were observed in 16/64 (25%) patients.

 

Butte (11) reported on a retrospective case series of 143 consecutive patients with T1 CRC undergoing polypectomy followed by colectomy (see Table 8). At colectomy, invasive residual disease was observed in 16 (11%) patients, non-invasive in 3 (2.1%) and lymph node metastasis in 10 (7%). Collectively, in 13% of patients residual disease was diagnosed at the moment of surgery. In case of positive or unknown resection margin, the rate of residual invasive disease in the colonic wall was 16% vs. 0% in case of a negative resection margin. After a median follow-up period of 63 months, no recurrences were identified; 122 patients were still alive, 15 died of unknown causes and 6 died of other causes.

 

Kim (12) followed retrospectively a case series of 64 patients with intramucosal CRC and 65 patients with submucosal CRC who all had either EMR (Endoscopic mucosal resection) or ESD (Endoscopic submucosal resection) performed (see Table 8). After a mean FU period of 19 months 62 patients with intramucosal CRC were still alive; 2 died of unrelated diseases. The survival rate for patients who had submucosal CRC was not reported. Seven patients with submucosal cancer had colectomy performed during the FU period, five because of positive resection margin or lymphovascular involvement, one because of bowel perforation and one patient requested surgery (see Table 8). The recurrence rate (i.e. local recurrence and/or distant recurrence) was 0/64 in the intramucosal group and 7/65 in the submucosal group (3/7 underwent colectomy and 4/7 only had polypectomy). Of the seven patients who suffered from recurrence, five had a high risk polyp and two a low risk polyp. The total number of high risk and low risk polyps included in the study is unclear.

Meining (13) documented on 390 patients with T1 CRC: 141 patients had polypectomy and surgical removal of T1 CRC (group A) and 249 only had polypectomy (group B)(see Table 8). Decision in favour or against surgery was based on risk patterns, patients’ personal wishes and patients’ fitness. Both low-risk and high-risk polyps were included in both groups. An unfavourable outcome was defined as locoregional cancer relapse, distant metastasis, lymph node metastasis or death related to CRC. In the polypectomy only group, an unfavourable outcome was observed in 17/249 (6.8%) patients. In this polypectomy only group, the rate of unfavourable outcome was 20% in case of incomplete resection versus 4% in case of complete resection; poorly differentiated tumours had an unfavourable outcome in 43% of cases versus 6% in other tumours and 44% of tumours with lymphovascular infiltration had an unfavourable outcome versus 5% in other cases.

 

Oka (14) reported on retrospective case series of 792 patients with submucosal CRC who only had surveillance after endoscopic resection (see Table 8). The data were collected from 15 centres in Japan. The recurrence rate was 18/792 (2.3%)(local recurrence: 11 cases and metastatic recurrence in 13 cases). The association between histopathological characteristics at polypectomy and recurrence was evaluated by means of a multivariate logistic regression analysis: lymphatic invasion was significantly associated with recurrence after ER in patients with submucosal CRC (OR: 6.36, 95% C.I. 1.46-27.79. It has to be mentioned though that this analysis was only based on 387 cases as the histopathological data were missing for 49% of the sample. The mean interval between ER and recurrence was 19.7 (+/- 9.2) months.

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.