Transcript Adjuvant Therapy of Non-Small Cell Lung Cancer 2007

Development of Lung Cancer Staging
Steven M. Keller, M.D.
Director Thoracic Surgery, Weiler Hospital
Professor of Cardiothoracic Surgery
Albert Einstein College of Medicine
Montefiore Medical Center, New York
Cancer Staging - Societies
• 1929 - League of Nations Health
Organization Cancer Commission
• 1933 - Union Internationale Contre le Cancer
(UICC)
• 1953 - International Commission on Stage
Grouping and Presentation of Results (ICPR)
at the International Congress of Radiology
• 1959 - American Joint Committee for Cancer
staging and End Results Reporting (AJC)
• 1980 - name changed to American Joint
Committee on Cancer (AJCC)
Originator of
TNM
Classification
Pierre Denoix, MD 1912-1990
L’Institut Gustave Roussy
Villejuif, France
Premises of TNM Staging
• TNM reflects the three significant events
in cancer growth
– Local Tumor Growth (T)
– Spread to Regional Lymph Nodes (N)
– Distant Metastases (M)
Objectives of the TNM Classification
• Aid the clinician in planning treatment
• Give some indication of prognosis
• Assist in evaluating the results of
treatment
• Facilitate the exchange of information
between treatment centers
• Contribute to continuing investigations
of human malignancies
History of TNM Staging
• 1954: UICC TNM Committee formed
• 1958-1967 UICC TNM Committee proposes
classifications for 23 body sites
• 1976: AJC National Cancer Conference on
Classification and Staging
• 1977: AJC Cancer Staging Manual (1st Edition)
• 1990: American College of Surgeons
Commission on Cancer mandates use of AJCCTNM Staging System for all approved Hospitals
• 2002: AJCC Cancer Staging Manual (6th Edition)
• 2009: AJCC Cancer Staging Manual (7th Edition)
Staging Systems Other Than TNM
Surveillance Epidemiology and End Results (SEER)
• 1973 - Established by the National Cancer
Institute following the passage of the National
Cancer Act of 1971
• Goals
– Collect complete and accurate data on all
cancers diagnosed among residents of
geographic areas covered by SEER cancer
registries
– Periodically report on the cancer burden as it
relates to cancer incidence and mortality, and
patient survival overall and in selected
segments of the population
Staging Systems Other Than TNM
Surveillance Epidemiology and End Results (SEER)
• Goals
– Identify unusual changes and differences in the
patterns of occurrence of specific forms of cancer
in population subgroups defined by geographic,
demographic, and social characteristics
– Describe temporal changes in cancer incidence,
mortality, extent of disease at diagnosis (stage),
therapy, and patient survival as they may relate to
the impact of cancer prevention and control
interventions.
– Monitor the occurrence of possible iatrogenic
cancers, i.e., cancers that are caused by cancer
therapy
SEER Data- Source and Accuracy
• 18 population based
cancer registries
• 26% U.S. population
• Reflects 2000 census
with regard to: race,
ethnicity, income, etc
• Regular audits and
training
SEER Summary Stage
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Developed 1977
Single digit definition
Less complex
Developed for registrars and epidemiologists
who want some information, but did not wish to
collect the more detailed Extent of Disease or
TNM data
• Utilizes best data available: clinical, radiologic,
pathologic
SEER Summary Stage
• Definitions
– In Situ (0)
– Localized only (1)
– Regional
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Direct extension only (2)
Lymph nodes only (3)
Both direct extension and lymph nodes (4)
Not otherwise specified (5)
– Distant organs or non-regional lymph nodes (7)
– Unknown (9)
SEER Extent of Disease
• Developed 1977 to assure consistency over
time as other staging systems changed
• Allow data to collapse into different and
previous staging systems
• Utilizes best data available: clinical, radiologic,
pathologic
• Five field, ten digit system
– Tumor size (three digits)
– Regional lymph node involvement (one digit)
– Number of pathologically reviewed lymph nodes that
contain tumor (two digits)
– Number of pathologically examined regional lymph
nodes (two digits)
Staging Systems Other Than TNM
Collaborative Staging
• Designed to bring together the TNM,
Summary Stage, and Extent of Disease
coding structures
• Initiated in 2004
• 9 data fields, 16 digits
• 5 additional site specific data fields
• Utilizes best data available: clinical, radiologic
or pathologic
Collaborative Staging
• Definitions
– Tumors size (three digits)
– Tumor extension (two digits)
– Method by which size and extension determined (one
digit)
– Regional lymph nodes (two digits)
– Method by which regional lymph node involvement
determined (one digit)
– Number of pathologically reviewed lymph nodes that
contained tumor (two digits)
– Number of pathologically examined regional lymph nodes
(two digits)
– Metastases at diagnosis (two digits)
– Method by which metastases determined (one digit)
Collaborative Staging
Lung Cancer Staging/Treatment
The Early Years 1933 - ~1974
• Surgery only potentially curative modality
• Cancer spreads in an orderly fashion from
primary site to region lymph nodes and then
to distant sites
Lung Cancer Staging/Treatment
The Early Years 1933 - ~1974
• Authors initially reported survival with and
without tumor in lymph nodes
• Gradual recognition that the presence of
disease in the “mediastinal” nodes had a
worse prognosis than metastases in the
“hilar” nodes
• No mention of tumor size, local invasion
• No mention of which lymph node involved
• Discussion regarding surgery if mediastinal
disease present
Task Force on Lung Cancer
of the American Joint
Committee on Cancer
Staging and End Reporting
Am J Radiol 1974;120;130-8
TNM Staging - 1st Edition
Definitions and Groupings
• T descriptor
– T0 no evidence tumor
– TX malignant cells but
tumor not seen
– T1 < 3cm, no visceral
pleural involvement,
distal to lobar bronchus
– T2 > 3cm or involves
visceral pleura, proximal
to bronchus. > 2 c from
carina, no effusion,
atelectasis < entire lung
– T3 direct extension to
adjacent organs, < 2 cm
from carina, atelectasis
entire lung
• N descriptor
– N0 no regional nodal
metastases
– N1 metastases to
ipsilateral hilar nodes
– N2 metastases to
mediastinal nodes
• M descriptor
– M0 no distant metastases
– M1 distant metastases
such as scale, cervical,
contralateral hilar nodes,
solid organs
Am J Radiol 1974;120;130-8
Survival Utilizing Clinical TNM
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T – 5 categories (T0-T3)
N – 3 categories (N0-N2)
M – 2 categories (M0-M1)
Stages – 3 (I-III)
• 2,155 patients
– 996 squamous
– 521 adenocarcinoma
– 195 large cell
– 368 small cell
– 75 undifferentiated
• All small cell cases
placed in stage 3
Am J Radiol 1974;120;130-8
Survival Utilizing Clinical TNM
*Small cell excluded
Am J Radiol 1974;120;130-8
Unified UICC/AJCC TNM Stage 1986
• Need for refinement recognized
• New categories created and grouping altered
• T – 7 categories (TX-T4)
• N – 4 categories (N0-N3)
• M – 2 categories (M0-M1)
• Stages – 7 (Occult carcinoma - IV)
Chest 1986;89:225S-33
Unified UICC/AJCC TNM Stage 1986
• 3,753 patients
– 2,749 MD Anderson
– 1004 LCSG
Chest 1986;89:225S-33
Unified UICC/AJCC TNM Stage 1997
• Need for refinement recognized
• New categories created and grouping altered
• T – 7 categories (TX-T4)
• N – 5 categories (NX-N3)
• M – 3 categories (MX-M1)
• Stage groupings – 8 (O - IV)
Chest 1997;111:1710-7
Unified UICC/AJCC TNM Stage 1997
Survival Clinical Stage
• 5,319 patients
– 4351 MD Anderson
– 968 LCSG
Lung Cancer: A Handbook for Staging, Imaging and Lymph
Node Classification. Mountain 1999
Revisions of the TNM Stage Groupings
for the Seventh Edition of the TNM
Classification
• 1998 International Association for the Study of
Lung Cancer (IASLC) established Lung Cancer
Staging Project
• Supported by the UICC and AJCC
• Data collected from 45 institutions in 20
countries on four continents
• Patients treated between 1990-2000
J Thorac Oncol 2006;1:281-6
Revisions of the TNM Stage Groupings
for the Seventh Edition of the TNM
Classification
• Total cases submitted 100,869
• Included in analysis 81,015
• Non-small cell lung cancer 67,725
• Small cell lung cancer 13,290
• New categories created and grouping altered
• T – 11 categories (TX-T4)
• N – 5 categories (NX-N3)
• M – 5 categories (MX-M2)
• Stage groupings – 8 (O - IV)
J Thorac Oncol 2007;2:706-14
Revisions of the T Descriptor
• T1 tumors divided into:
– T1a (< 2cm in greatest dimension)
– T1b (>2cm<3cm in greatest dimension)
• T2 tumors divided into:
– T2a (>3cm<5cm in greatest dimension)
– T2b (>5cm<7cm in greatest dimension)
• Tumors >7cm in greatest dimension added to
the T3 category
J Thorac Oncol 2007;2:593-602
Revisions of the T Descriptor
• Satellite nodules in the same lobe moved to
T3 (previously T4)
• Metastases in other ipsilateral lobes moved to
T4 (previously M1)
• Pleural metastases (malignant pleural or
pericardial effusions, pleural nodules) moved
to M1a (previously T4)
J Thorac Oncol 2007;2:593-602
Japanese Nodal Definitions
Tsuguo Naruke, MD
JTCVS 1978;76:832-39
Mountain Dresler Lymph Node Map
Level 2R
Level 2L
Level 4R superior
Level 4L
Level 4R inferior
Level 12R
Level 10R
Level 11R
Chest 1997;111:17178-23
Level 10L
Level 8L
Level 9L
Revisions of the N Descriptor
• No change in
descriptors
• Zones consisting of
multiple levels
correlate with
survival
• ? Define N by zone
or combination of
zones
Upper zone (R)
AP Zone (L)
Subcarinal zone
Lower zone
Hilar zone
Peripheral zone
J Thorac Oncol 2007;2:603-12
Revisions of the M Descriptor
• M1a
– Pleural metastases (malignant pleural or pericardial
effusions, pleural nodules) (previously T4)
– Metastases in the contralateral lung
• M1b
– Distant metastases (outside lung and pleura)
J Thorac Oncol 2007;2:686-93
Revisions of the Stage Groupings
• T2aN1 now IIA (changed from IIB)
• T2bN0 now stage IIA (changed from IB)
• T4N0 and T4N1 now IIIA (changed from IIIB)
J Thorac Oncol 2007;2:706-14
Staging - Special Circumstances
• Visceral pleural involvement – at least T2a
• Multiple synchronous tumors in single organ –
stage most advanced and indicate multiple in
parenthesis ex: T2a(2)N0
• Multiple synchronous tumors in paired organ –
stage and report independently
Staging - Special Circumstances
• Lymph node replacement – use best judgment
• Lymph node direct extension – stage as
metastatic disease
• Lymph node disease < 2mm classify as pN0
• Doubt – use lower stage
• Recurrent nerve injury – nodes (N2) vs
primary (T4)
Clinical Stage - Definition
• Information obtained prior to instituting
therapy or within 4 months of diagnosis,
whichever is shorter
• Includes:
– Physical exam
– Radiology
– Laboratory
– Biopsy: any type, any method
Clinical Staging - Definition
• Clinical T – includes any biopsy and
even surgical exploration without
resection, unless the biopsy proves the
highest T category (T4)
• Clinical N - In the absence of pT,
excision of single or sentinel node is cN
• Clinical Stage
– Absence of pT and pN
– Absence of pM1
Pathologic Staging
• Information about extent of cancer
obtained up through completion of
definitive surgery therapy or within 4
months of diagnosis, whichever is
longer
Pathologic Staging - Definition
• Pathologic T
– Resection
– Biopsy that proves highest T category (T4)
• Pathologic N
– Any node if, pT present
– Single node, if highest category (N3)
– In the absence of pT, excision of single or sentinel node is
cN
• Pathologic Stage
• If both pT and pN present, M1 may be cM1 or pM1
• If pM1 present, T and N may be clinical or pathologic
Staging- Limitations
• TNM was originated by a surgeon (Denoix)
based on the teachings of another surgeon
(Halstead)
• No surprise that TNM is most applicable to
patients whose primary and most effective
treatment is surgery
• TNM is a temporal model that does not take
into account other factors that predict response
to treatment (surgery, chemotherapy,
radiotherapy, other)
Staging: What is Needed
• Staging system that incorporates new
information that predicts survival
– Genomics
– Proteomics
– Immunohistochemistry