1. AJCC 7th Edition of Gastric Cancer: good enough?
Deon Chong
North District Hospital

2. Ideal cancer staging - Aim
Treatment planning
Assessing prognosis
Stratifying patients for therapeutic studies
Evaluating the results of treatment
Facilitating communication

3. Ideal cancer staging - Aim
Treatment planning
Assessing prognosis
Stratifying patients for therapeutic studies
Evaluating the results of treatment
Facilitating communication

4. TNM Staging - History TNM Pierre Denoix UICC 1st Ed 4th Ed UICC + AJCC
TNM
Pierre Denoix
UICC
1968
1st Ed
1987
4th Ed
UICC + AJCC
1974
1978
2nd Ed
3rd Ed
2009
7th Ed
5th,6th Ed

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

6. Outline Changes in AJCC 7th Ed for gastric cancer: Meet the aim?
T stage
N stage
M stage
Meet the aim?

7. Outline Changes in AJCC 7th Ed for gastric cancer: Meet the aim?
T stage
N stage
M stage
Meet the aim?

8. Ca Stomach – T stage AJCC 6th Ed AJCC 7th Ed 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 7th Ed
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

9. Ca Stomach – T stage AJCC 6th Ed AJCC 7th Ed 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 7th Ed
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

10. 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 polarity
Glandular architectural abnormalities
- Complex budding, branching and back-to-back glands
Oesohagogastric surgery
A companion to specialist surgical practice 4th Ed

11. Ca Stomach – Tis stage Consensus conferences: - Vienna classification
Category 1
Negative for neoplasia/dysplasia
Category 2
Indefinite for neoplasia/dysplasia
Category 3
Non invasive neoplasia, low grade
Category 4
Non-invasive neoplasia, high grade
4.1 High grade adenoma/dysplasia
4.2 Non-invasive carcinoma (carcinoma in situ)
4.3 Suspicious for invasive carcinoma
Category 5
Invasive neoplasia
5.1 Intramucosal carcinoma
5.2 submucosal carcinoma
From/
Gut 2000;47:251-5

12. Ca Stomach – Tis stage This new Tis staging solves the controversy
Implies a less conservative management towards high grade dysplasia

13. Ca Stomach – T stage AJCC 6th Ed AJCC 7th Ed 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 7th Ed
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

14. Ca Stomach – T1 stage Incidence of nodal metastasis T1a
(mucosal tumor)
3% (0.7-21%)
T1b
(submucosal tumor)
20% ( %)
Br J Surg1992;79:241-4 Br J Surg 2002;89:
Br J Surg 1990;77: Br J Surg 1995;82:952-6
Cancer 1995;76: Br J Surg 1996;83:1421-3
Ann Surg 2007;129:714-9

15. Better at Predicting Prognosis
Ca Stomach – T1 stage
Incidence of nodal metastasis
T1a
(mucosal tumor)
3% (0.7-21%)
T1b
(submucosal tumor)
20% ( %)
Br J Surg1992;79:241-4 Br J Surg 2002;89:
Br J Surg 1990;77: Br J Surg 1995;82:952-6
Cancer 1995;76: Br J Surg 1996;83:1421-3
Ann Surg 2007;129:714-9
Better at Predicting Prognosis

16. Ca Stomach – T1 stage Recent advances in EMR and ESD: Suitable tumor:
Elevated or flat lesions <2cm size
Depressed lesions <1cm without ulceration
Mucosal invasion
Well differentiated
No lymphatic permeation
Oesohagogastric surgery
A companion to specialist surgical practice 4th Ed

17. Guide Our Treatment Plan
Ca Stomach – T1 stage
Recent advances in EMR and ESD:
Suitable tumor:
Elevated or flat lesions <2cm size
Depressed lesions <1cm without ulceration
Mucosal invasion
Well differentiated
No lymphatic permeation
Guide Our Treatment Plan

18. Ca Stomach – T stage AJCC 6th Ed AJCC 7th Ed 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 7th Ed
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

19. Ca Stomach – T2-4 stage
Depth of tumor invasion is one of the most important predictors for prognosis
Ann Surg 1998;228:449-61
Surg Gynrcol Obstet 1986;162(3):229-34
Lancet 2003;362:305-15
Ann Surg 2005;241:27-39
Serosal importance

20. 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;70:1030-7
Cancer 2000;89:255-61
Cancer 1996;77:2445-8
Serosal importance
Br J Surg 1990;77:436-9

21. Better at Predicting Prognosis
Ca Stomach – T stage
AJCC 6th Ed
AJCC 7th Ed T2
Tumor invades the muscularis propria or subserosa T3
Tumor invades serosa T4
Tumor invades adjacent strutures
AJCC 6th Ed T2
Tumor invades the muscularis propria T3
Tumor penetrates the subserosa
T4a
Tumor invades serosa
T4b
Tumor invades adjacent stuctures
Better at Predicting Prognosis

22. Ca Stomach – T stage
The new T staging is better stratified to predict prognosis and guide our treatment

23. Outline Changes in AJCC 7th Ed for gastric cancer: Meet the aim?
T stage
N stage
M stage
Meet the aim?

24. Ca Stomach – N stage
LN status is the most important prognostic indicator
Berlin: Springer.1995,47-64
Ann Surg 1998;228:449-61

25. Ca Stomach – N stage
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)

26. Ca Stomach – N stage
Japanese believe that tumor growth inside the regional LN could reflect tumor aggressiveness
Ann Surg Oncol 2000;7:750-7

28. NOT SIMPLE

29. NOT EASILY REPRODUCIBLE

30. Ca Stomach – N stage NOT EASILY REPRODUCIBLE: For Surgeons
D2/3 lymphadenectomy should be performed in order to complete the nodal staging
paper

31. Ca Stomach – N stage 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
paper

32. Ca Stomach – N stage
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 Staging

33. Ca Stomach – N stage
5th AJCC N staging was more simple, reproducible and sensitive in the prognostic evaluation than the JCGC N staging
Cancer 2000;88:
Br J Surg 1994;81:414-4
Surg Gynecol Obstet 1990;170:488-94
Ai Zheng 2005;24:596-9
Arch Surg 1992;127:290-4
Retained in 6th Ed

34. Ca Stomach – N stage
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;16:61-7
J Surg Oncol 2006;94:274-80
Dig Surg 2003;20:148-53
Gut 1996;38:525-7
J Clin Oncol 1993;11:
Chin Med J 2007;120:

35. Ca Stomach – N stage AJCC 6th Ed AJCC 7th Ed Nx
Regional LN cannot be assessed N0
No regional LN mets N1
Mets in 1-6 regional LN N2
Mets in 7-15 regional LN N3
Mets in >15 regional LN
AJCC 6th Ed Nx
Regional LN cannot be assessed N0
No regional LN mets N1
Mets in 1-2 regional LN N2
Mets in 3-6 regional LN
N3a
Mets in 7-15 regional LN
N3b
Mets in ≥ 16 regional LN

36. 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

37. Ca Stomach – N stage Stage Migration
7th Ed N stage still has the same limitation as in 5th/6th Ed
Stage Migration

38. Ca Stomach – N stage Stage Migration
7th Ed N stage still has the same limitation as in 5th/6th Ed
Stage Migration
Instances in which evaluation of an inadequate number of LN leads to understaging and subsequent underestimation of disease severity

39. Ca Stomach – N stage Stage Migration
7th Ed N stage still has the same limitation as in 5th/6th Ed
Stage Migration
Observed in about 10-15% of cases, especially in less extensive lymphadenctomy
Ann Surg Oncol 2002;9:775-84
Ann Surg Oncol 2003;10:
J Clin Oncol 1995;13:19-25
N Engl J Med 1985;312:1604-8
Arch Surg 1988;123:1023-4

40. Ca Stomach – N stage Stage Migration
7th Ed N stage still has the same limitation as in 5th/6th Ed
Stage Migration
In an analysis of US SEER data from , the median number of LN examined was 8 and <25% of patients had ≥15 nodes examined
J Clin Oncol 2005;23:

41. Ca Stomach – N stage Stage Migration Mets LN Ratio
7th Ed N stage still has the same limitation as in 5th/6th Ed
Stage Migration
Mets LN Ratio

42. Ca Stomach – N stage LN ratio:
- number of positive LN over the number of examined LN

43. Ca Stomach – N stage 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;7:200
J Clin Oncol 1995;13:19-25
Cancer 1999;86:553-8
Cancer 1998;82:621-31
Br J Surg 1991;78:825-7

44. Ca Stomach – N stage

45. Ca Stomach – N stage
D2 or D3

46. Future studies required
Ca Stomach – N stage
Limitations of LN ratio:
- cut off of LN ratio intervals
- present studies compared with 5th/6th Ed
Future studies required

47. Ca Stomach – N stage
The new N staging is better than 6th Ed in prognosis prediction but controversy is still present

48. Outline Changes in AJCC 7th Ed for gastric cancer: Meet the aim?
T stage
N stage
M stage
Meet the aim?

49. Ca Stomach – M stage AJCC 6th Ed AJCC 7th Ed Mx
Distant mets cannot be assessed M0
No distant mets M1
Distant mets
- Non regional or distant LN
Peritoneal surfaces
Other organs
AJCC 7th Ed
AJCC 6th Ed M0
No distant mets M1
Distant mets
- Positive peritoneal cytology
- Non regional or distant LN
Peritoneal surfaces
Other organs

50. Ca Stomach – M stage AJCC 6th Ed AJCC 7th Ed Mx
Distant mets cannot be assessed M0
No distant mets M1
Distant mets
- Non regional or distant LN
Peritoneal surfaces
Other organs
AJCC 7th Ed
AJCC 6th Ed M0
No distant mets M1
Distant mets
- Positive peritoneal cytology
- Non regional or distant LN
Peritoneal surfaces
Other organs

51. Ca Stomach – M stage Mx is deleted in 7th Ed
- Lack of information about metastatic status is considered inappropriate

52. Ca Stomach – M stage 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

53. Ca Stomach – M stage AJCC 6th Ed AJCC 7th Ed Mx
Distant mets cannot be assessed M0
No distant mets M1
Distant mets
- Non regional or distant LN
Peritoneal surfaces
Other organs
AJCC 7th Ed
AJCC 6th Ed M0
No distant mets M1
Distant mets
- Positive peritoneal cytology
- Non regional or distant LN
Peritoneal surfaces
Other organs

54. Better at Predicting Prognosis
Ca Stomach – M stage
Prognosis of patients with positive peritoneal cytology is very poor:
- 5 year survival rate is less than 5%
Hepatoenterol 2001;48:892-4
J Surg Oncol 2009;99:324-8
Ann Surg Oncol 2001;8:215-21
Better at Predicting Prognosis

55. Alter Our Staging Process?
Ca Stomach – M stage
Imply the systematic use of staging laparoscopy + evaluation of peritoneal lavage fluid?
Alter Our Staging Process?

56. Ca Stomach – M stage
The new M staging is better in predicting prognosis and possibly alter our staging process

57. 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.

58. The current TNM staging reflects the anatomical extent of the tumor
The current TNM staging reflects the anatomical extent of the tumor. But we know certain non anatomical factors, such as cell type, tumor grading and lympovascular permeation affect prognosis. So, should the future TNM staging include these non anatomical factors?
Need studies to confirm whether they are independent factor using multivariate analysis

59. Qn:
OGJ staging- in previous 6th ed, there was no statement on whether it shd be staged under eso or stomach,
Stage grouping
THE END

60. 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!

61. AJCC 6th Ed
AJCC 7th Ed
Stage 1a T1N0M0 Stage 1b T2a/bN0M0 T1N1M0 Stage 2 T1N2M0 T2aN1M0 T2bN1M0 T3N0M0 Stage 3a T2aN2M0 T2bN2M0 T3N1M0 T4N0M0 Stage 3b T3N2M0 Stage 4 T4N1M0 T4N2M0 T4N3M0 T1N3M0 T2N3M0 T3N3M0 any T any N M1
Stage 1a T1N0M0 Stage 1b T2N0M0 T1N1M0 Stage 2a T3N0M0 T2N1M0 T1N2M0 Stage 2b T4aN1M0 T3N1M0 T2N2M0 T1N3M0 Stage 3a T4bN0M0 T3N2M0 T2N3M0 Stage 3b T4bN0M0 T4bN1M0 T4aN2M0 T3N3M0 Stage 3c T4bN2M0 T4bN3M0 T4aN3M0 Stage 4 any T any N M1
Could appear as a result of optimism towards new therapeutic strategies for locally advanced disease