Table Of Content1
Evidenced-based Guideline
for Colorectal Cancer
Version 1.1 – August 2014
AWMF-Registration Number: 021/007OL
© Leitlinienprogramm Onkologie | Evidenced-based Guideline for Colorectal Cancer | August 2014
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Table of Contents
1. Information on this Guideline .......................................................... 9
1.1. Editors .................................................................................................................................. 9
1.2. Leading Professional Society .................................................................................................. 9
1.3. Guideline Funding ................................................................................................................. 9
1.4. Contact ................................................................................................................................. 9
1.5. Citation Method .................................................................................................................... 9
1.6. Special Note ........................................................................................................................ 10
1.7. Goal of the German Guideline Program in Oncology ............................................................. 10
1.8. Guideline Authors ............................................................................................................... 11
1.8.1. Composition of the Guideline Group 2011/2012 ................................................................. 11
1.8.2. Coordinators of the Guideline Group 2007/2008 ................................................................. 14
1.8.3. Composition of the Task Force Quality Indicators ................................................................ 14
1.8.4. Methodological Support....................................................................................................... 14
1.9. Available Documents on the Guideline and Implementation ................................................. 15
2. Introduction .................................................................................. 16
2.1. Scope and Purpose .............................................................................................................. 16
2.1.1. Goal and Issues ................................................................................................................... 16
2.1.2. Audience ............................................................................................................................. 17
2.1.3. Period of Validity and Update Processes ............................................................................... 17
2.2. Basis for the Method ........................................................................................................... 17
2.2.1. Scheme of Evidence Level According to Oxford .................................................................... 17
2.2.2. Scheme of the Grade of Recommendation ............................................................................ 20
2.2.3. Clinical Evaluation – Classification of the Grade of Recommendation .................................... 20
2.2.4. Classification of the Degree of Consensus ........................................................................... 21
2.2.5. Statements .......................................................................................................................... 21
2.2.6. Good Clinical Practice (GCP) ................................................................................................. 21
2.2.7. Independence and Declaration of Possible Conflict of Interest .............................................. 21
2.3. Abbreviations Used ............................................................................................................. 22
2.4. Editorial Note: ..................................................................................................................... 23
3. Prevention Asymptomatic Population .............................................. 24
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3.1. Lifestyle Habits .................................................................................................................... 24
3.2. Diet Recommendations ........................................................................................................ 25
3.3. Micronutrients ..................................................................................................................... 29
3.4. Drugs .................................................................................................................................. 30
4. Screening Asymptomatic Population ............................................... 33
4.1. Screening -Age ................................................................................................................... 33
4.2. Methods of Colorectal Screening/Prevention ........................................................................ 33
4.2.1. Endoscopic Methods ............................................................................................................ 34
4.2.1.1. Colonoscopy ................................................................................................................ 34
4.2.1.2. Sigmoidoscopy ............................................................................................................ 35
4.2.1.3. Capsule-Colonoscopy .................................................................................................. 36
4.2.2. Stool Tests .......................................................................................................................... 37
4.2.2.1. Fecal Occult Blood Test (FOBT) ..................................................................................... 37
4.2.2.2. Genetic Screening Tests ............................................................................................... 39
4.2.2.3. M2-PK ......................................................................................................................... 40
4.2.3. Radiologic Tests .................................................................................................................. 41
4.3. Cost Effectiveness ............................................................................................................... 41
4.4. Recommendations of Other Included Guidelines .................................................................. 42
5. Risk Groups ................................................................................... 43
5.1. Sporadic Colorectal Cancer .................................................................................................. 43
5.1.1. Risk Groups ........................................................................................................................ 43
5.1.1.1. Relatives of Patients with Colorectal Cancer .................................................................. 43
5.1.1.2. Relatives of Patients with Colorectal Adenomas ............................................................ 44
5.1.1.3. Patients with Colorectal Adenomas ............................................................................... 44
5.1.2. Primary Prevention .............................................................................................................. 46
5.1.3. Screening Tests ................................................................................................................... 46
5.1.3.1. First-degree Relatives of Patients with Colorectal Cancer .............................................. 46
5.1.3.2. Relatives of Patients with Colorectal Adenomas ............................................................ 48
5.2. Hereditary Colorectal Cancer ............................................................................................... 48
5.2.1. Risk Groups ........................................................................................................................ 49
5.2.1.1. HNPCC (Hereditary Colorectal Cancer Without Polyposis)/ Lynch-Syndrome .................. 49
5.2.1.2. Adenomatous Polyposis-Syndrome .............................................................................. 52
5.2.1.2.1. Patients with Classic Familial Adenomatous Polyposis (FAP) ...................................... 52
5.2.1.2.2. Patients with Attenuated Familial Adenomatous Polyposis (AFAP) .............................. 53
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5.2.1.2.3. Patients with MUTYH-Associated Polyposis (MAP) ..................................................... 53
5.2.2. Screening ............................................................................................................................ 54
5.2.2.1. HNPCC / Lynch-Syndrome ........................................................................................... 54
5.2.2.2. Adenomatous Polyposis Syndromes.............................................................................. 59
5.2.2.2.1. Patients with Classic Familial Adenomatous Polyposis (FAP) ...................................... 59
5.2.2.2.2. Patients with Attenuated Familial Adenomatous Polyposis......................................... 64
5.2.2.2.3. Patients with MUTYH-Associated Polyposis (MAP) ..................................................... 65
5.2.2.3. Non-Adenomatous Polyposis-Syndromes ..................................................................... 68
5.3. Chronic Inflammatory Bowel Diseases .................................................................................. 70
5.3.1. Colitis Ulcerosa ................................................................................................................... 70
5.3.2. Crohn's Disease................................................................................................................... 72
5.4. Appendix: Figures and Tables of TK III ................................................................................. 73
5.4.1. Algorithmus: Genetic diagnostics and screening .................................................................. 73
5.4.2. Diagnostic algorithm immunohistochemistry / MSI for work up of mismatch-repair-defect .. 74
5.4.3. Recommended Screening Programs for HNPCC .................................................................... 75
5.4.4. Spigelman-Classification ..................................................................................................... 75
6. Endoscopy: Implementation and Management of Polyps ................... 76
6.1. Role of Endoscopy in the Diagnostics of Polyps and CRC ...................................................... 76
6.1.1. Sigmoidoscopy Versus Colonoscopy .................................................................................... 77
6.1.2. Chromoendoscopy .............................................................................................................. 78
6.1.3. Magnifying Endoscopy ......................................................................................................... 79
6.2. Polypectomy ........................................................................................................................ 79
6.2.1. Removal of Polyps by Snare Versus Forceps ......................................................................... 79
6.3. Histologic Examination ........................................................................................................ 82
6.4. Approach for pT1 Cancer .................................................................................................... 83
6.5. Polyp Management (Follow-Up) ........................................................................................... 85
6.6. Medical Secondary Prevention of Adenomas ......................................................................... 88
7. Pre-operative Diagnostics and Surgery ............................................ 89
7.1. Introduction ........................................................................................................................ 89
7.2. Definition of Colon and Rectal Cancer .................................................................................. 89
7.3. Definition Interdisciplinary Tumor Conference ..................................................................... 89
7.4. Pre-Operative Evaluation ..................................................................................................... 91
7.4.1. Endoscopic Diagnostics ....................................................................................................... 91
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7.4.2. Imaging Procedures ............................................................................................................. 93
7.4.2.1. The Relevance of Individual Imaging Procedures (except PET) for the Evaluation of Distant
Metastases in the Primary Treatment of CRC ................................................................ 93
7.4.2.2. Relevance of Pre-Operative Local Staging Using CT (MRI) for Colon Cancer with Regard to
Local Spread ................................................................................................................ 94
7.4.2.3. Relevance of PET-CT .................................................................................................... 94
7.4.2.3.1. For Primary Diagnosis of Colorectal Cancer .............................................................. 94
7.4.2.3.2. Before Resection of Colorectal Liver Metastases ........................................................ 95
7.4.3. Tumor Markers.................................................................................................................... 97
7.4.4. Specific Diagnostics for Rectal Cancer .................................................................................. 98
7.5. Surgical Therapy with Curative Intention ............................................................................ 101
7.5.1. Intraoperative Staging ....................................................................................................... 101
7.5.1.1. Intra-Operative Pathological Examination ................................................................... 101
7.5.2. Radical Surgical Therapy of Colon Cancer .......................................................................... 102
7.5.2.1. Extent of Lymph Node Dissection: .............................................................................. 102
7.5.2.2. Complete Mesocolic Excision (CME) ............................................................................ 104
7.5.2.3. Local Ablative Therapies for Liver Metastases ............................................................. 105
7.5.2.3.1. Radio-Frequency Ablation (RFA) ............................................................................. 105
7.5.2.3.2. Selective Internal Radiation Therapy (SIRT) .............................................................. 105
7.5.2.3.3. Laser Induced Interstitial Thermotherapy (LITT) ...................................................... 106
7.5.3. Radical Surgical Therapy of Rectal Cancer .......................................................................... 106
7.5.3.1. General Oncologic Principles ...................................................................................... 106
7.5.3.2. Approach to Tumors of the Upper Third of the Rectum ............................................... 107
7.5.3.3. Approach to Tumors of the Middle and Lower Third of the Rectum ............................. 108
7.5.3.4. Reconstruction After Total Mesorectal Excision ........................................................... 109
7.5.3.5. Decision to Preserve the Sphincter.............................................................................. 110
7.5.3.6. Approach in Case of Complete Response after Neoadjuvant Therapy .......................... 111
7.5.3.7. Rectal-Exstirpation .................................................................................................... 111
7.5.4. Stoma-Construction .......................................................................................................... 112
7.5.5. Local Excision of Rectal Cancers ........................................................................................ 114
7.6. Laparoscopic Surgery ........................................................................................................ 115
7.7. Special Situations .............................................................................................................. 116
7.7.1. Surgical Therapy of Peritoneal Carcinomatosis ................................................................... 116
7.7.2. Multivisceral Resection ...................................................................................................... 116
7.7.3. Multiple Cancers of the Colon and Rectum ......................................................................... 117
7.7.4. Emergency Surgery ............................................................................................................ 117
7.7.5. Resection of Liver Metastases ............................................................................................ 117
7.7.6. Extensive Distant Metastazation and Asymptomatic Primary Tumor.................................... 118
7.7.7. Patients with HNPCC (Hereditary Non-Polyposis Colorectal Cancer) .................................... 119
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7.7.8. Cancers in Familial Adenomatous Polyposis (FAP) .............................................................. 120
7.7.9. Cancers in Ulcerative Colitis .............................................................................................. 120
7.8. Postoperative Histopathological Examination ..................................................................... 121
7.8.1. Cancer-Grading Based on MSI-H ....................................................................................... 121
7.8.2. Number of LN to be Removed ............................................................................................ 122
7.8.3. Relevance of Distance Between the Tumor Margin and Resection Area of the Mesocolon in
Colon Cancer ................................................................................................................. 123
7.8.4. Relevance of Distance From the Circumferential Resection Margin (CRM-Classification) with
Colon and Rectal Cancer ................................................................................................. 125
7.8.5. Relevance of Documenting the Quality of the TME-Preparation .......................................... 126
7.9. Psychooncological Aspects ................................................................................................ 127
8. Adjuvant and Neoadjuvant Therapy ............................................... 129
8.1. Adjuvant Therapy of Colon Cancer ..................................................................................... 129
8.1.1. Indications for Adjuvant Therapy of Colon Cancer .............................................................. 129
8.1.2. Age Limitations for Conducting Adjuvant Chemotherapy .................................................... 129
8.1.3. UICC Stage III .................................................................................................................... 130
8.1.4. UICC Stage II ..................................................................................................................... 130
8.1.5. UICC Stage II with Risk Factors ........................................................................................... 131
8.1.6. Chemotherapy Protocols.................................................................................................... 134
8.1.6.1. Stage III ..................................................................................................................... 134
8.1.6.2. Stage II ...................................................................................................................... 136
8.2. Perioperative Therapy of Rectal Cancer .............................................................................. 137
8.2.1. Indications for Perioperative Radiotherapy or Radiochemotherapy ...................................... 137
8.2.1.1. Stage I ....................................................................................................................... 137
8.2.1.2. Stage II/III .................................................................................................................. 138
8.2.2. Adjuvant Therapy .............................................................................................................. 141
8.2.2.1. Adjuvant Therapy After Primary Surgery (without neoadjuvant therapy) ....................... 141
8.2.2.2. Adjuvant Therapy After Neoadjuvant Radiotherapy or Radiochemotherapy .................. 144
9. Management of Patients with Metastases and in the Palliative Situation
................................................................................................. 146
9.1. Primarily Resectable Liver and/or Pulmonary Metastases .................................................... 147
9.1.1. Primarily Resectable Pulmonary Metastases ........................................................................ 147
9.1.2. Primarily Resectable Liver Metastases ................................................................................ 148
9.1.2.1. Preoperative Imaging ................................................................................................. 150
9.1.2.2. Perioperative Therapy of Primarily Resectable Liver Metastases ................................... 152
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9.1.2.2.1. Neoadjuvant Therapy of Resectable Liver Metastases .............................................. 152
9.1.2.2.2. Adjuvant Therapy of Resectable Liver Metastases.................................................... 153
9.2. Patients with an Indication for Intensified Systemic Therapy ............................................... 158
9.2.1. Patients with Potentially Resectable Metastases .................................................................. 158
9.2.1.1. Management of Isolated Primarily Irresectable Pulmonary Metastases ......................... 158
9.2.1.2. Management of Isolated Primarily Irresectable Liver Metastases .................................. 158
9.2.1.2.1. Systemic Neoadjuvant Therapy ............................................................................... 158
9.2.1.2.2. Chemotherapy Consequences on the Healthy Liver Tissue and Metastasis Localization
..................................................................................................................... 160
9.2.1.2.3. Local ablative therapies for liver metastases ........................................................... 161
9.2.2. Patients with an Indication for Intensified Palliative Therapy ............................................... 163
9.3. Patients with the Option for Less Intensive Therapy ........................................................... 163
9.4. Chemotherapy Protocols.................................................................................................... 164
9.4.1. First-Line Therapy ............................................................................................................. 164
9.4.1.1. Monotherapy (5-FU) ................................................................................................... 165
9.4.1.2. Combination Therapy ................................................................................................. 166
9.4.2. Duration of Therapy / Interruption of Therapy in First-line Therapy / Reinduction ............. 174
9.4.3. Chemotherapy Protocols in Second- and Third-Line Therapy ............................................. 176
9.4.3.1. Combination Therapy in Second- and Third-line Therapy ........................................... 177
9.4.3.2. Monotherapy with Biological Substances in Third-Line Therapy .................................. 179
9.5. Procedure for Local Recurrence or for Non-hepatic and Non-pulmonary Distant Metastazation
......................................................................................................................................... 180
9.5.1. Local Recurrence ............................................................................................................... 180
9.5.2. Non-Hepatic or Non-Pulmonal Distant Metastases ............................................................. 180
10. Follow-up Care ............................................................................ 182
10.1. Follow-Up for Patients with UICC stage I ............................................................................ 182
10.2. Follow-Up for Patients with UICC stage II and III ................................................................. 183
10.3. Role of Diagnostic Methods for Follow-up ......................................................................... 184
10.3.1. Medical History .............................................................................................................. 184
10.3.2. CEA Testing ................................................................................................................... 184
10.3.3. Other Laboratory Parameters .......................................................................................... 185
10.3.4. FOBT .............................................................................................................................. 186
10.3.5. Ultrasound ..................................................................................................................... 186
10.3.6. Endoscopic Ultrasound ................................................................................................... 187
10.3.7. Chest X-Ray ................................................................................................................... 187
10.3.8. Computer Tomography .................................................................................................. 188
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10.3.9. Endoscopic Procedures ................................................................................................... 189
10.3.9.1. Colonoscopy .............................................................................................................. 189
10.3.9.2. Sigmoidoscopy .......................................................................................................... 189
10.3.9.3. Rectoscopy ................................................................................................................ 189
10.3.10. Colon Contrast Enema, Virtual Colonography, and PET .................................................... 191
10.4. Time Course of Follow-up ................................................................................................. 192
10.5. Age Limit for Follow-up..................................................................................................... 192
10.6. Special Cases .................................................................................................................... 192
10.7. Rehabilitation After Resection of Colorectal Cancer ............................................................ 194
10.8. Tertiary Prevention ............................................................................................................ 195
10.8.1. Care Continuity and Continuation of the Health Promoting Activities after Acute Therapy and
Rehabilitation ................................................................................................................. 195
10.8.1.1. Improvement of Care Continuity ................................................................................. 195
10.8.1.2. Continuation of Health Promoting Activities ............................................................... 195
10.8.2. Tertiary Prevention: Physical Activity, Nutrition, as well as Complementary and Alternative
Therapy ......................................................................................................................... 196
10.8.2.1. Physical Activity ......................................................................................................... 196
10.8.2.2. Nutrition .................................................................................................................... 196
10.8.2.3. Complementary and Alternative Medicine ................................................................... 196
10.8.2.4. Alternative Healing Methods....................................................................................... 197
11. Quality Indicators ........................................................................ 199
12. Appendix .................................................................................... 203
12.1. UICC-Classification of Colorectal Cancer ........................................................................... 203
12.2. Amsterdam Criteria ........................................................................................................... 204
12.3. Revised Bethesda-Criteria.................................................................................................. 204
13. List of Figures .............................................................................. 205
14. List of Tables ............................................................................... 205
15. References .................................................................................. 207
© Leitlinienprogramm Onkologie | Evidenced-based Guideline for Colorectal Cancer | August 2014
1. Information on this Guideline 9
1. Information on this Guideline
1.1. Editors
German Guideline Program in Oncology (GGPO) of the AWMF, German Cancer Society,
and German Cancer Aid
1.2. Leading Professional Society
German Society for Digestive and Metabolic Diseases (DGVS)
Steering committee for development and implementation through the DGVS:
Univ.-Prof. Dr. Wolff Schmiegel
Dr. Christian P. Pox
1.3. Guideline Funding
This guideline was funded by the German Cancer Aid as part of the German Guideline
Program in Oncology.
1.4. Contact
Office of the German Guideline Program in Oncology
c/o German Cancer Society
Kuno-Fischer St. 8
D-14057 Berlin
1. Information on this Guideline 10
1.6. Special Note
Medicine is continuously developing. Therefore, all information, especially diagnostic
and therapeutic procedures, only corresponds to the knowledge at the time the
guideline is published. The greatest possible care was taken with the
recommendations on therapy as well as choice and dose of drugs. Nonetheless, the
users are requested to call on the manufacturer's instruction leaflet and the SmPC
and in case of doubt to consult a specialist. In the GGPO-editors' general interest,
relevant discrepancies should be reported.
The users are responsible for each diagnostic and therapeutic application,
medication, and dosage.
In this guideline registered trademarks (protected trade names) have not been
specifically marked. Therefore, it cannot be concluded from the missing of such a
reference that it is a free trade name.
The copyright of the document is protected in all parts. Any use outside of the
Copyright Protection Law is not allowed and illegal without written agreement of the
German Guideline Program in Oncology (GGPO). No part of the document may be
reproduced in any form without written permission of the GGPO. This holds in
particular for copies, translations, microfiche, as well as the saving, use, and
exploitation in electronic systems, intranets, and the internet.
1.7. Goal of the German Guideline Program in Oncology
With the German Guideline Program in Oncology (GGPO), the committee of the
Scientific Medical Professional Societies (AWMF), the German Cancer Society (DKG), and
the German Cancer Aid (DKH) have the goal to fund and support the development,
update, and implementation of evidence-based and practical oncologic guidelines. The
program is based on medical-scientific knowledge of the professional societies and the
DKG, the consensus of medical experts, users and patients, as well as regulations of
the guideline preparation of the AWMF and the expert support and funding by the
German Cancer Aid. To show the current medical knowledge and to take medical
progress into consideration, guidelines have to be reviewed and updated. The AWMF-
regulations will be used as a basis for the development of high quality oncologic
guidelines. Since guidelines are an important quality assurance and quality
management tool in oncology, they should be specifically and sustainably
implemented in routine care. Thus, active implementation measures and evaluation
programs are an important aspect of the GGPO-support. The goal of the program is to
establish professional and intermediately funded prerequisites for the development
and preparation of high quality guidelines in Germany. These high-grade guidelines
serve not only the structured transfer of knowledge, but they may also find their place
in health care system structuring. Worth mentioning here are evidence-based
guidelines as the basis for preparing and updating disease management programs or
for the implementation of quality indicators taken from guidelines for the certification
of organ tumor centers.
© Leitlinienprogramm Onkologie | Evidenced-based Guideline for Colorectal Cancer | August 2014
