TN Categorization for Rectal and Colon Cancers Based on National Survival Outcome Data LL Gunderson1, JM Jessup 2, DJ Sargent 3, FL Greene 4, A Stewart 5 for the AJCC Hindgut Taskforce (HTF) 1Mayo Clinic Cancer Center – Arizona; Scottsdale, AZ 2National Cancer Institute, Rockville, MD 3Mayo Clinic Cancer Center – Rochester; Rochester, MN 4Carolinas Medical Center; Charlotte, NC 5American College of Surgeons; Chicago, IL

Colorectal Cancer – TN Categorization Background AJCC 6th Edition: Added outcomes-based substaging Stage II subdivided: IIA (T3N0M0) and IIB (T4N0M0) Stage III subdivided: IIIA (T1-2N1), IIIB (T3-4N1), IIIC (TanyN2) Rectal Pooled Analyses: Outcomes supported revised substaging of Stage III T1-2N2 cancers - survival and relapse similar to T4N0 (IIB) or T3N1 (IIIA) T4N1 cancers – survival and relapse similar to T3N2 and T4N2 AJCC Hindgut Taskforce - sought validation in a population-based dataset that depth of invasion interacts with nodal status to affect survival

Colorectal CA – Rectal Pooled Analysis Survival and Relapse Rates by Risk for Relapse Category^

Colorectal CA – SEER Population-Based Analysis Methods – Patient Group/Tumor Stratification SEER Population-based data: Jan 1, 1992 to Dec, 2004 Patient Group: Rectal CA – 35,829 patients, Colon CA – 109,953 patients Tumor Stratification Extent of disease: T4N0 stratified by ‘Tumor penetrates the surface of visceral peritoneum’ (T4a) vs. ‘Tumor invades or is adherent to adjacent organs or structures’ (T4b) Number of positive nodes (+ LN) N1a (1 LN+) vs. N1b (2-3 LN+) N2a (4-6 LN+) vs. N2b (≥7 LN+)

Colon CA – TN Categorization, SEER Analysis Survival Results by TN Category, # LN+, # LN Examined

Colon CA – TN Categorization, SEER Analysis Survival Results by TN Category, # LN+, # LN Examined

Rectal CA – TN Categorization, SEER Analysis Survival by Expanded TN Category, TNM Stg I-IIIA

Rectal CA – TN Categorization, SEER Analysis Survival by Expanded TN Category, TNM Stg IIIB-IIIC

Colorectal CA – TN Categorization, SEER Analysis Survival by Expanded TN Category, Rectum vs Colon

Colorectal CA – Survival by TN Category, SEER Analyses Proposed Changes – AJCC Staging, 7th Edition

Colorectal CA – TN Categorization, SEER Analysis Summary of 5-yr Observed Survival by TN Category T4a lesions have better prognosis than T4b Rectal 5-yr Obs Surv: N0, 55.7 vs. 44.7% ; N1, 48.2 vs. 24.3% Colon 5-yr Obs Surv: N0, 60.6 vs. 45.7% ; N1, 47.0 vs. 27.9% T1-2N2 lesions have better prognosis than T3-4N2 Rectal 5-yr Obs Surv: 56.1% vs. 37.5% (T3N2) & 26.4% (T4N2) Colon 5-yr Obs Surv: 61.5% vs. 38.1% (T3N2) & 21.7% (T4N2) T4bN1 cancers have prognosis more akin to T4N2 than T4aN1 Rectal 5-yr Obs Surv: 24.3 vs. 26.4 (T4N2) vs. 48.2% (T4aN1) Colon 5-yr Obs Surv: 27.9 vs. 21.7 (T4N2) vs. 47.0% (T4aN1) Prognosis by nodal status: Related to both number of LN+ and number of LN examined

Colorectal CA – TN Categorization, SEER Analysis Conclusions SEER population-based analyses validates Rectal Pooled Analysis Supports shift of T1-2N2 lesions from IIIC to IIIA/IIIB Supports shift of T4bN1 from IIIB to IIIC SEER outcomes support sub-staging of T4, N1 and N2 T4a has better prognosis than T4b for N0, N1, N2 categories N1a (1 LN+) has better prognosis than N1b (2-3 LN+) N2a (4-6 LN+) has better prognosis than N2b (> 7 LN+) SEER outcomes support revised substaging of Stg II & III Subdivide current IIB into IIB(T4aN0) or IIC(T4bN0) Shift more favorable TN2 categories to earlier stages IIIA – T1N2a IIIB – T1N2b, T2N2a-b, T3N2a, T4aN2a Survival Outcomes by TN category More similar for rectal and colon cancer than expected Suggest a complex biological interaction between depth of invasion and nodal status