Understanding Esophageal Cancer Staging Thomas W. Rice MD
Purposes of Staging Treatment planning Prognostication Research Communication
TNM
Pierre Denoix (1912 1990) Cancer Institute Gustave-Roussy 1943 1952 conceived TNM
1 ST Edition Stage Groupings 1977 T IS T1 T2 T3 N0 I I II III N1 III III III III M1 III III III III
2 nd Edition Stage Groupings 1983 Stage 0 Tis N0 M0 Stage IV Any T Any N M1
3rd 6th Edition T and N Classifications
3 rd 6 th Edition Stage Grouping T1 T2 T3 T4 N0 I IIA IIA III N1 IIB IIB III III
4 th Edition Stage Groupings 1997 M1 Sub-classifications M1a M1b Stage IV Sub-groupings IVA IVB
2010 AJCC/UICC 7 th Edition Staging
AJCC Requests If possible Data driven staging of esophageal cancer Addition of non-anatomic (non-tnm) cancer characteristics Harmonization of esophageal and gastric staging
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The Data
Data for Stage Groupings Dataset n = 7,885 Subset for staging Surgery alone n = 4,723 No preoperative chemo and/or radiotherapy No postoperative chemo- or radiotherapy Mucosal cancers only ptnm
Demographics 100 80 60 40 20 0 Age Men White Asian Other Rice TW, et al. Dis of the Eso 2009;22:1-8.
Histopathologic Cell Type Adenocarcinoma 60% Squamous Cell Carcinoma 40% Undifferentiated.15%
Histologic Grade G1 32% G2 33% G4.18% G3 35%
Esophageal Location Lower Third 69% Upper Third 4% Middle Third 27%
pt 100 80 % 60 40 20 0 Tis T1 T2 T3 T4
pn 100 80 % 60 40 20 0 N0 N+
Positive Lymph Nodes 100 80 % 60 40 20 0 0 1 2 3 4 5 6 >7
pm M0 92% M1 8%
Survival Univariable Correlates
Survival 100 80 % 60 40 20 0 0 2 4 6 8 10 Years Rice TW, et al. Dis of the Eso 2009;22:1-8.
Survival (%) Survival - Cell Type 100 80 60 40 20 Undifferentiated Adenocarcinoma Squamous 0 0 2 4 6 8 10 Years
Survival (%) Survival Histologic Grade 100 80 60 40 20 G4 G1 G2 G3 0 0 2 4 6 8 10 Years
Survival (%) Survival - Location 100 80 60 40 20 Lower Middle Upper 0 0 2 4 6 8 10 Years
Survival (%) Survival - pt 100 80 60 ptis pt1 40 20 pt2 pt3 0 0 2 4 6 8 10 Years pt4
Survival (%) Survival - Positive Lymph Nodes 100 80 60 0 40 20 5 >6 0 0 2 4 6 8 10 Years 1 2 3 4
Survival (%) Survival - pm 100 80 60 pm0 40 20 pm1a pm1b 0 0 2 4 6 8 10 Years
The Results
Summary of Changes Cancer location Simplified EGJ/cardia/subcardia added and harmonization with gastric Rice TW, et al. Cancer 2010;16:3763-73.
Survival - Location 100 80 % 60 40 20 0 0 Lower Middle Upper 2 4 6 8 10 Years
Summary of Changes Non-anatomic cancer features H (histopathologic type) G (histologic grade)
Survival - Histopathologic Cell Type 100 80 % 60 40 Adenocarcinoma 20 Undifferentiated Squamous 0 0 2 4 6 8 10 Years
Survival (%) Survival Histologic Grade 100 80 60 40 20 G4 G1 G2 G3 0 0 2 4 6 8 10 Years
Summary of Changes T Tis redefined T4 subclassified
Summary of Changes N Regional lymph node redefined N subclassified by number of positive nodes
Survival (%) Survival - Positive Lymph Nodes 100 80 60 0 40 20 5 >6 0 0 2 4 6 8 10 Years 1 2 3 4
Summary of Changes M Redefined
Site-specific Factors Distance to proximal edge of tumor from incisors Distance to distal edge of tumor from incisors Number of regional lymph nodes with extracapsular
Additional Descriptors and Treatment Decision Descriptor LVI Residual tumor (R) Treatment Planning Clinical stage used National guidelines used
Final Stage Groupings Esophageal Adenocarcinoma
Additional Non-TNM Characteristics
Adenocarcinoma G1-2 G 3 T1 T2 N0 IA IB IB IIA
Adenocarcinoma G1-2 G 3 N0 T4 T1 T2 T3 a b IIB IIIA IIIC N1 IIB IIB IIIA IIIC IIIC N2 IIIA IIIA IIIB IIIC IIIC N3 IIIC IIIC IIIC IIIC IIIC
Adenocarcinoma G1-2 G 3 N0 N1 T4 T1 T2 T3 a b IA IB IB IIA IIB IIIA IIIC IIB IIB IIIA IIIC IIIC N2 IIIA IIIA IIIB IIIC IIIC N3 IIIC IIIC IIIC IIIC IIIC
Survival - Adenocarcinoma 100 % 80 60 40 0 IA IB IIA 20 0 0 2 4 6 8 10 Years IIB IIIA IIIB IIIC
Squamous Cell Carcinoma T1 G1 IA G2-3 IB
Squamous Cell Carcinoma T2-T3 G1 IB IIA Cancer Location Lower Upper Middle G2-3 IIA IIB
Squamous Cell Carcinoma T4 T1 T2 T3 a b N0 IIIA IIIC N1 IIB IIB IIIA IIIC IIIC N2 N3 IIIA IIIA IIIB IIIC IIIC IIIC IIIC IIIC IIIC IIIC
Survival - Squamous cell 100 80 % 60 40 20 IA 0 IB IIA IIB IIIA IIIB IIIC 0 0 2 4 6 8 10 Years ca AJCC
8 th Edition AJCC/UICC Esophageal and EGJ Cancer Staging
AIM 1 Refine and expand staging AJCC
Refine and Expand Staging A) Obtaining better homogeneity of Stage 0 and Stage IV. This requires abandoning the restrictive definitions of these stage groupings and changing composition of adjacent Stage IA and Stage IIIC
Survival Homogeneity (%) Adenocarcinoma 100 80 60 97.8 96.3 94.5 100 76.5 88.2 90.3 72.4 40 20 0 0 IA IB IIA IIB IIIA IIIB IIIC
Survival Homogeneity (%) Squamous Cell Carcinoma 100 80 60 89.2 100 100 82.6 64.6 87.9 90.1 72.5 40 20 0 0 IA IB IIA IIB IIIA IIIB IIIC
Refine and Expand Staging B) Improving homogeneity of Stage IIB adenocarcinoma and Stage IIA and IIB squamous cell cancer. This requires expanding our database of these less common cancers.
Survival Homogeneity (%) Adenocarcinoma 100 80 60 97.8 96.3 94.5 100 76.5 88.2 90.3 72.4 40 20 0 0 IA IB IIA IIB IIIA IIIB IIIC
Survival Homogeneity (%) Squamous Cell Carcinoma 100 80 60 89.2 100 100 82.6 64.6 87.9 90.1 72.5 40 20 0 0 IA IB IIA IIB IIIA IIIB IIIC
Refine and Expand Staging C) Adding staging classifications clinical (cstage) post-induction clinical and postdefinitive nonsurgical clinical (ycstage) post-induction pathologic (ypstage) staging This requires expanding the data analysis.
Refine and Expand Staging D) Assessing other non-anatomic tumor characteristics that affect survival. This requires expanding data elements beyond histopathologic cell type, histologic grade and cancer location.
Refine and Expand Staging E) Adding non-esophagectomy survival data endoscopic treatment in Stage 0, IA palliative therapy in Stage IV. This requires partnering with nonsurgical specialties and professional associations and groups.
Refine and Expand Staging F) Adding cancer of the cervical esophagus. This requires partnering and harmonizing with the head and neck task force, mirroring the process used with the gastric cancer task force in the 7th edition.
AIM 2 Develop clinical decision-making model Decision Model DEC
Decision Model A) Construct validated models for cancer recurrence death Based on variables known at the time of treatment decision making patient characteristics clinical stage (cstage and ycstage) additional cancer characteristics
Decision Model B) Estimate probability of downstaging clinical classifications (ctnm and yctnm) and stage groupings (cstage and ycstage) by various types, schedules, and combinations of preoperative adjuvant therapy.
Decision Model C) Program a smart phone-based strategic decision support tool based on clinical stage (cstage and ycstage) to estimate time-related cancer recurrence and death for different treatment options.
AIM 3 Create a personalized, patient-specific prognostic tool Prognostic Model PROG
Prognostic Model A) Construct validated models for cancer recurrence death Based on variables known at the time of treatment patient characteristics refined post treatment stage (ycstage) or pathologic stage (pstage or ypstage) additional cancer characteristics
Prognostic Model B) Program a smart phone-based strategic personalized prognostic tool based on post-treatment stage (ycstage, pstage and ypstage) and treatment received to estimate cancer recurrence and death for individual patients.
AJCC DEC PROG Bridge Tango Malbec Beef Football
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ricet@ccf.org