1. Slides last updated: March 2015 CRC: STAGING

2. How colorectal cancer (CRC) is staged 1 Stage describes the extent of cancer, and is one of the most important factors in determining prognosis and treatment options For CRC, stage is based on how far the cancer has grown into the intestinal wall, if it has reached nearby structures, and if it has spread to distant organs Clinical staging uses results of the physical exam, biopsy and imaging tests. Pathologic staging combines these tests with results from surgery Staging is the process of determining how far the cancer has spread, and involves physical exam, biopsies, imaging tests and results of surgery 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.

3. TNM classification is the most commonly used system 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. Primary tumour (T) Growth Regional lymph nodes (N) Distant metastasis (M) Spread Metastasis

4. The TNM staging system for CRC: T 1 T categories describe the extent of spread through the layers that form the wall of the colon and rectum These layers, from inner to outer, include: Mucosa – inner lining Muscularis mucosa – a thin muscle layer Submucosa – the fibrous tissue beneath this muscle layer Muscularis propria – a thick muscle layer that contracts to force the contents of the intestines along Subserosa and serosa – the thin outermost layers of connective tissue that cover most of the colon 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.

5. The TNM staging system for CRC: T 1 Tx: No description is possible due to incomplete information Tis: The cancer is at its earliest stage (in situ) and involves only the mucosa; it has not grown beyond the muscularis mucosa T1: The cancer has grown through the muscularis mucosa and extends into the submucosa T2: The cancer has grown through the submucosa and extends into the muscularis propria T3: The cancer has grown through the muscularis propria and into the outermost layers of the colon or rectum, but not through them T4a: The cancer has grown through the serosa, the outermost lining T4b: The cancer has grown through the wall of the colon or rectum and is attached to or has invaded nearby tissue or organs 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.

6. The TNM staging system for CRC: N 1 N categories indicate whether the cancer has spread to nearby lymph nodes, and if so, how many lymph nodes may be involved For an accurate estimation of lymph node involvement, ≥12 lymph nodes are removed during surgery and examined under a microscope Nx: No description is possible N0: No cancer cells in nearby lymph nodes N1: Cancer cells found in 1-3 nearby lymph nodes N1a: 1 lymph node N1b: 2-3 lymph nodes N1c: Small deposits of cells found in areas of fat near lymph nodes, but not in the nodes themselves N2: Cancer cells found in ≥4 nearby lymph nodes N2a: 4-6 lymph nodes N2b: ≥7 lymph nodes 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.

7. The TNM staging system for CRC: M 1 M categories indicate whether the cancer has spread (metastasised) to distant organs such as the liver, lungs or distant lymph nodes M0: No distant spread is seen M1a: Cancer has spread to one distant organ or set of lymph nodes M1b: Cancer has spread to more than one distant organ or set of lymph nodes, or to distant parts of the peritoneum (lining of the abdominal cavity) 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. Once the T, N and M categories have been determined – usually after surgery – the information is combined in a process called stage grouping Stages range from stage I (least advanced) to stage IV (most advanced)

8. Stages in CRC 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. Cancer progression Stage IVA Any T, any N, M1a Stage IVA Any T, any N, M1b Stage 0 Tis, N0, M0 Stage I T1-T2, N0, M0 Stage IIA T3, N0, M0 Stage IIB T4a, N0, M0 Stage IIC T4b, N0, M0 Stage IIIA T1-T2, N1, M0 T1, N2a, M0 Stage IIIB T3-T4a, N0, M0 T2-T3, N2a, M0 T1-T2, N2b, M0 Stage IIIC T4b, N0, M0 T3-T4a, N2b, M0 T4b, N1-N2, M0

9. Survival rates for CRC by stage 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. Refers to the percentage of patients who live at least 5 years after diagnosis Relative survival rates compare observed survival with what would be expected without cancer Five-year relative survival rate

10. Grades of CRC 1 Survival is also affected by the grade of cancer Grade describes how closely the cancer looks like normal tissue when viewed under a microscope Grade 1 (G1): cancer looks much like normal colorectal tissue Grade 4 (G4): cancer looks very abnormal Grades 2 and 3 (G2 and G3) fall in between G1 and G4 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. Often simplified to either low grade (G1, G2) or high grade (G3, G4) Low-grade cancers tend to grow and spread more slowly than high- grade cancers The outlook for low-grade cancers tends to be better than for high-grade cancers