1. Slides last updated: June 2015 CRC: CLINICAL FEATURES

2. CRC diagnosis includes several assessments 1 1.American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015. Complete medical history, as well as family history Physical exam to look for masses in the abdomen and enlarged organs Blood tests Colonoscopy Biopsy and lab tests of samples Imaging tests

3. Colonoscopy and blood tests 1 1.American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015. 2.Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72. Colonoscopy: Main procedure for diagnosis 2 Can determine the exact location, detect further lesions and remove polyps If a complete colonoscopy is not possible, colonoscopy of the rectum and sigmoid colon should be combined with a barium enema 2 Blood tests: Complete blood count – to detect anaemia Liver enzymes – to assess liver function Tumour markers – most commonly in patients with a history of CRC

4. Tests of biopsy samples and imaging tests 1 1.American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015. Tests of biopsy samples: Gene tests – to detect specific mutations that impact treatment decisions, e.g., KRAS MSI testing – detection of microsatellite instability may identify conditions such as HNPCC and affect treatment choice Imaging tests: CT scans, ultrasounds, MRI scans and PET scans – to assess the presence and spread of cancer Chest X-ray – to check if cancer has spread to the lungs Angiography – to visualise blood supply to the cancer (particularly relevant if cancer has spread to the liver)

5. Some common CRC symptoms 1,2 Most people with early CRC do not display symptoms of the disease. Symptoms are typically associated with relatively large tumours and/or advanced stages and tend not to be specific to the disease It is very important to discuss any potential CRC symptoms with a healthcare provider Change in bowel habits (persistent diarrhoea, constipation or narrowing of stool) Unexplained weight loss Rectal bleeding Weakness and fatigue Cramping and abdominal pain Blood in faeces (that may lead to darker faeces than normal) Iron deficiency and anaemia 1.American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015. 2.Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.

6. Screening aims to find benign adenomas or early CRC 1,2 1.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2014. Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 17/03/2015. 2.Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72. Screening tests can be structural or faecal-based Structural -Colonoscopy – most complete screening procedure -Flexible sigmoidoscopy – limited to the lower part of the bowel -Computed tomographic colonography (CTC) – virtual colonoscopy, under evaluation Faecal-based -Faecal occult blood tests (FOBT) – test for blood in faeces; can be guaiac-based (gFOBT) or immunochemical (iFOBT or FIT) -Stool DNA test – test for known DNA alterations during CRC progression, under evaluation

7. NCCN (US) screening recommendations 1 A risk-based approach is recommended, with patients assigned to one of the following categories: Average risk -≥50 years of age -Negative family history -No history of adenoma, CRC or inflammatory bowel disease Increased risk -Either a personal history of adenomas or sessile serrated polyps (SSPs), CRC or inflammatory bowel disease -Or a positive family history of CRC or advanced adenomas High-risk syndromes -Either a family history of HNPCC -Or a personal or family history of polyposis syndromes 1.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 16/06/2015. 2.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf, last accessed on 16/06/2015.

8. NCCN (US) screening recommendations 1 Guidance is provided for the following groups: Average risk -Recommended screening options include colonoscopy every 10 years annual faecal-based tests flexible sigmoidoscopy every 5 years with or without an interval faecal-based test at year 3 Increased risk or high-risk syndromes -Surveillance programme tailored to the patient’s personal history and preferences as well as their detailed family history -Screening intervals (mostly colonoscopy) adjusted to match each case 1.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 16/06/2015. 2.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf, last accessed on 16/06/2015.

9. ESMO (European) screening recommendations 1 Guidance for average-risk populations is provided: Screening interval for gFOBT should not be >2 years -if iFOBT, the interval should be the same as for gFOBT or <3 years Screening interval for flexible sigmoidoscopy and colonoscopy should not be <10 years and can be extended to 20 years New screening techniques such as CTC and stool DNA tests are still under evaluation and not recommended for screening in the average-risk population 1.Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.