ajcc 7 th edition of gastric cancer: good enough? deon chong north district hospital

AJCC 7th Edition of Gastric Cancer:good enough?

Deon ChongNorth District Hospital

Ideal cancer staging - Aim

• Treatment planning• Assessing prognosis• Stratifying patients for therapeutic studies• Evaluating the results of treatment• Facilitating communication

TNM Staging - History

1943-1952

TNM

Pierre Denoix UICC

1968

1st Ed TNM

1987

4th Ed TNM

UICC + AJCC

1974 1978

2nd EdTNM

3rd EdTNM

2009

7th EdTNM

5th,6th Ed

Does the 7th Ed for gastric cancer meet the aim of staging?

Outline

• Changes in AJCC 7th Ed for gastric cancer:– T stage– N stage– M stage

Meet the aim?

Ca Stomach – T stage

Tis Intraepithelial tumor without invasion of the lamina propria

T1 Tumor invades lamina propria or submucosa

T2 Tumor invades the muscularis propria or subserosa

T3 Tumor invades serosa

T4 Tumor invades adjacent strutures

AJCC 6th Ed

Tis Intraepithelial tumor without invasion of the lamina propria (including high grade dysplasia)

T1a Tumor invades lamina propria or muscularis mucosae

T1b Tumor invades submucosa

T2 Tumor invades the muscularis propria

T3 Tumor penetrates the subserosa

T4a Tumor invades serosa

T4b Tumor invades adjacent stuctures

AJCC 6th EdAJCC 6th Ed AJCC 7th EdAJCC 7th Ed

Ca Stomach – Tis stage

• In the past, there was controversy for definitions of high grade tumor and Ca in-situ

Western pathologist

Diagnosis of invasive cancer:Definite invasion of malignant cells into the lamina propria before they consider that the basement membrane has been breached

Japanese pathologist

Diagnosis of cancer:Nuclear factors- enlargement, pleomorphism, prominent necleoli and loss of polarityGlandular architectural abnormalities- Complex budding, branching and back-to-back glands

Oesohagogastric surgeryA companion to specialist surgical practice 4th Ed


• Consensus conferences:- Vienna classification

Category 1Negative for neoplasia/dysplasiaCategory 2Indefinite for neoplasia/dysplasiaCategory 3Non invasive neoplasia, low gradeCategory 4Non-invasive neoplasia, high grade4.1 High grade adenoma/dysplasia4.2 Non-invasive carcinoma (carcinoma in situ)4.3 Suspicious for invasive carcinomaCategory 5Invasive neoplasia5.1 Intramucosal carcinoma5.2 submucosal carcinoma

Category 1Negative for neoplasia/dysplasiaCategory 2Indefinite for neoplasia/dysplasiaCategory 3Non invasive neoplasia, low gradeCategory 4Non-invasive neoplasia, high grade4.1 High grade adenoma/dysplasia4.2 Non-invasive carcinoma (carcinoma in situ)4.3 Suspicious for invasive carcinomaCategory 5Invasive neoplasia5.1 Intramucosal carcinoma5.2 submucosal carcinoma Gut 2000;47:251-5


• This new Tis staging solves the controversy • Implies a less conservative management

towards high grade dysplasia







AJCC 6th Ed









Ca Stomach – T1 stage

T1a(mucosal tumor)

3% (0.7-21%)

T1b(submucosal tumor)

20% (10.6-64%)

Incidence of nodal metastasis

Br J Surg1992;79:241-4 Br J Surg 2002;89:1035-42Br J Surg 1990;77:1330-4 Br J Surg 1995;82:952-6Cancer 1995;76:935-40 Br J Surg 1996;83:1421-3Ann Surg 2007;129:714-9


T1a(mucosal tumor)

3% (0.7-21%)

T1b(submucosal tumor)

20% (10.6-64%)

Incidence of nodal metastasis

Br J Surg1992;79:241-4 Br J Surg 2002;89:1035-42Br J Surg 1990;77:1330-4 Br J Surg 1995;82:952-6Cancer 1995;76:935-40 Br J Surg 1996;83:1421-3Ann Surg 2007;129:714-9

Better at Predicting PrognosisBetter at Predicting Prognosis


• Recent advances in EMR and ESD:

Suitable tumor:Elevated or flat lesions <2cm sizeDepressed lesions <1cm without ulcerationMucosal invasionWell differentiated No lymphatic permeation


Oesohagogastric surgeryA companion to specialist surgical practice 4th Ed


• Recent advances in EMR and ESD:



Guide Our Treatment PlanGuide Our Treatment Plan







AJCC 6th Ed









Ca Stomach – T2-4 stage

• Depth of tumor invasion is one of the most important predictors for prognosis

Ann Surg 1998;228:449-61Surg Gynrcol Obstet 1986;162(3):229-34Lancet 2003;362:305-15Ann Surg 2005;241:27-39

Ca Stomach – T2-4 stage

• Serosal invasion correlates with early recurrence and short survival period

• Transcoelomic dissemination and direct infiltration of adjacent structures may occur as a result of serosal involvement

Cancer 1992;70:1030-7Cancer 2000;89:255-61Cancer 1996;77:2445-8

Br J Surg 1990;77:436-9





AJCC 6th Ed




T4b

Tumor invades adjacent stuctures




The new T staging is better stratified to predict prognosis and guide our treatment

The new T staging is better stratified to predict prognosis and guide our treatment

Outline


Meet the aim?

Ca Stomach – N stage

• LN status is the most important prognostic indicator

Berlin: Springer.1995,47-64Ann Surg 1998;228:449-61


• N stage of 4th Ed of AJCC was based on anatomical location of the involved LN, according to the Japanese Classification of Gastric Cancer (JCGC)


• Japanese believe that tumor growth inside the regional LN could reflect tumor aggressiveness

Ann Surg Oncol 2000;7:750-7

NOT SIMPLENOT SIMPLE

NOT EASILY REPRODUCIBLENOT EASILY REPRODUCIBLE


• NOT EASILY REPRODUCIBLE:For Surgeons

D2/3 lymphadenectomy should be performed in order to complete the nodal stagingD2/3 lymphadenectomy should be performed in order to complete the nodal staging


• NOT EASILY REPRODUCIBLE:For Pathologist

Assessment of the distance to edge of primary tumor may be variable due to shrinking of the tumor free gastric wall after resection and formalin fixation

Assessment of the distance to edge of primary tumor may be variable due to shrinking of the tumor free gastric wall after resection and formalin fixation


• In 1997, UICC/AJCC used the number of met LN in N staging for a more uniform and comparable system for western and Japanese

5th Ed AJCC Staging5th Ed AJCC Staging


• 5th AJCC N staging was more simple, reproducible and sensitive in the prognostic evaluation than the JCGC N staging

Cancer 2000;88:1796-800Br J Surg 1994;81:414-4Surg Gynecol Obstet 1990;170:488-94Ai Zheng 2005;24:596-9Arch Surg 1992;127:290-4

Retained in 6th EdRetained in 6th Ed


• 5th/6th Ed N staging was criticized for inappropriate cut-off of the N number, especially in N1, for homogeneity and prediction of prognosis

Ann Surg Oncol 2009;16:61-7J Surg Oncol 2006;94:274-80Dig Surg 2003;20:148-53Gut 1996;38:525-7J Clin Oncol 1993;11:1894-900Chin Med J 2007;120:2268-70


Nx Regional LN cannot be assessed

N0 No regional LN mets

N1 Mets in 1-6 regional LN


N3 Mets in >15 regional LN

AJCC 6th Ed

Nx Regional LN cannot be assessed

N0 No regional LN mets



N3a Mets in 7-15 regional LN

N3b Mets in ≥ 16 regional LN


• Univariate analysis: 7th Ed N stage, 5th/6th Ed N stage and JCGC N stage were associated with overall survival

• Multivariate analysis, only 7th Ed N stage is an independent factor

• Using case control matched fashion, 7th Ed N stage is also superior in prognostic prediction


• 7th Ed N stage still has the same limitation as in 5th/6th Ed

Stage MigrationStage Migration




Instances in which evaluation of an inadequate number of LN leads to understaging and subsequent underestimation of disease severity




Observed in about 10-15% of cases, especially in less extensive lymphadenctomy

Ann Surg Oncol 2002;9:775-84Ann Surg Oncol 2003;10:1077-85J Clin Oncol 1995;13:19-25N Engl J Med 1985;312:1604-8Arch Surg 1988;123:1023-4




In an analysis of US SEER data from 1973-1999, the median number of LN examined was 8 and <25% of patients had ≥15 nodes examined

J Clin Oncol 2005;23:7114-24




Mets LN RatioMets LN Ratio


• LN ratio:- number of positive LN over the number of examined LN


• LN ratio is minimally influenced by:- the extent of the lymphadenectomy - the pathologist’s accuracy in looking for an adequate number of nodes

BMC Cancer 2007;7:200J Clin Oncol 1995;13:19-25Cancer 1999;86:553-8Cancer 1998;82:621-31Br J Surg 1991;78:825-7


D2 or D3D2 or D3


• Limitations of LN ratio:- cut off of LN ratio intervals- present studies compared with 5th/6th Ed

Future studies requiredFuture studies required


The new N staging is better than 6th Ed in prognosis prediction but controversy is

still present

The new N staging is better than 6th Ed in prognosis prediction but controversy is

still present

Outline


Meet the aim?

Ca Stomach – M stage

Mx Distant mets cannot be assessed

M0 No distant mets

M1 Distant mets- Non regional or distant LN- Peritoneal surfaces- Other organs

AJCC 6th Ed

M0 No distant mets

M1 Distant mets- Positive peritoneal cytology- Non regional or distant LN- Peritoneal surfaces- Other organs



• Mx is deleted in 7th Ed- Lack of information about metastatic status is considered inappropriate


• Use of Mx could jeopardize:- results of apparently curative surgery- reliability of evaluation of response after neoadjuvant/adjuvant therapy- reliability of follow-up programs

Ann Surg Oncol 2010 Sept 29


Mx Distant mets cannot be assessed

M0 No distant mets

M1 Distant mets- Non regional or distant LN- Peritoneal surfaces- Other organs

AJCC 6th Ed

M0 No distant mets

M1 Distant mets- Positive peritoneal cytology- Non regional or distant LN- Peritoneal surfaces- Other organs



• Prognosis of patients with positive peritoneal cytology is very poor:- 5 year survival rate is less than 5%

Hepatoenterol 2001;48:892-4J Surg Oncol 2009;99:324-8Ann Surg Oncol 2001;8:215-21



• Imply the systematic use of staging laparoscopy + evaluation of peritoneal lavage fluid?

Alter Our Staging Process?Alter Our Staging Process?


The new M staging is better in predicting prognosis and possibly alter our staging process

The new M staging is better in predicting prognosis and possibly alter our staging process

AJCC 7th Edition of Gastric Cancer:good enough?

Conclusion:• This new TNM Staging is superior in assessing prognosis. • T stage guides our treatment and the M stage may alter our staging process. • N stage still remains controversial.

THE END

OGJ Tumor

• In AJCC 6th Ed: No clear statement on whether we should stage OGJ tumor as Ca eso or ca stomach- ie: it could be staged as either Ca eso or Ca stomach- since the N stages were different, the prognostic groupings were different

• In AJCC 7th Ed: It is now staged under Ca eso- harmonised!

Stage 1a T1N0M0Stage 1b T2a/bN0M0

T1N1M0Stage 2 T1N2M0

T2aN1M0T2bN1M0T3N0M0

Stage 3a T2aN2M0T2bN2M0T3N1M0T4N0M0

Stage 3b T3N2M0Stage 4 T4N1M0

T4N2M0T4N3M0T1N3M0T2N3M0T3N3M0any T any N M1

Stage 1a T1N0M0Stage 1b T2N0M0

T1N1M0Stage 2a T3N0M0

T2N1M0T1N2M0

Stage 2b T4aN1M0T3N1M0T2N2M0T1N3M0

Stage 3a T4bN0M0T3N2M0T2N3M0

Stage 3b T4bN0M0T4bN1M0T4aN2M0T3N3M0

Stage 3c T4bN2M0T4bN3M0T4aN3M0

Stage 4 any T any N M1

AJCC 6th Ed AJCC 7th Ed

ajcc 7 th edition of gastric cancer: good enough? deon chong north district hospital

Documents

th ed slide

th ed ajcc

th ed tisintraepithelial

th ed tnm uicc ajcc

nd ed tnm

rd ed tnm

lamina propria t1tumor

muscularis propria t3tumor