LLG03999

TN Categorization for Rectal and Colon Cancers Based on National Survival Outcome Data

1Mayo Clinic Cancer Center – Arizona; Scottsdale, AZ2National Cancer Institute, Rockville, MD

3Mayo Clinic Cancer Center – Rochester; Rochester, MN4Carolinas Medical Center; Charlotte, NC

5American College of Surgeons; Chicago, IL

1Mayo Clinic Cancer Center – Arizona; Scottsdale, AZ2National Cancer Institute, Rockville, MD

3Mayo Clinic Cancer Center – Rochester; Rochester, MN4Carolinas Medical Center; Charlotte, NC

5American College of Surgeons; Chicago, IL

LL Gunderson1, JM Jessup 2, DJ Sargent

3,FL Greene

4, A Stewart 5

for the AJCC Hindgut Taskforce (HTF)

LL Gunderson1, JM Jessup 2, DJ Sargent

3,FL Greene

4, A Stewart 5

for the AJCC Hindgut Taskforce (HTF)

LLG03999

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

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

LLG03999

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

LLG03999

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+)

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+)

LLG03999

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

LLG03999

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

LLG03999

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

LLG03999

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

LLG03999

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

LLG03999

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

LLG03999

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+ andnumber of LN examined

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+ andnumber of LN examined

LLG03999

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 IIICSEER 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 – T1N2aIIIB – 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

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 IIICSEER 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 – T1N2aIIIB – 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