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)

Pierre Denoix, MD 1912-1990

L’Institut Gustave Roussy

Villejuif, France

Originator of TNM

Classification

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 AJCC-TNM Staging System for all approved Hospitals

• 2002: AJCC Cancer Staging Manual (6th Edition)• 2009: AJCC Cancer Staging Manual (7th Edition)

Staging Systems Other Than TNMSurveillance 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 TNMSurveillance 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

• 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

• 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 TNMCollaborative 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/TreatmentThe 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

• 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

Lung Cancer Staging/TreatmentThe Early Years 1933 - ~1974

Am J Radiol 1974;120;130-8

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 EditionDefinitions and Groupings

• N descriptor– N0 no regional nodal

metastases– N1 metastases to

ipsilateral hilar nodes– N2 metastases to

mediastinal nodes

• 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

• 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

• 2,155 patients– 996 squamous– 521 adenocarcinoma– 195 large cell– 368 small cell– 75 undifferentiated

• All small cell cases placed in stage 3

• T – 5 categories (T0-T3)• N – 3 categories (N0-N2)• M – 2 categories (M0-M1)• Stages – 3 (I-III)

Survival Utilizing Clinical TNM

Am J Radiol 1974;120;130-8*Small cell excluded

Chest 1986;89:225S-33

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)

Unified UICC/AJCC TNM Stage 1986

• 3,753 patients– 2,749 MD Anderson– 1004 LCSG

Chest 1986;89:225S-33

Chest 1997;111:1710-7

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)

Lung Cancer: A Handbook for Staging, Imaging and Lymph Node Classification. Mountain 1999

Unified UICC/AJCC TNM Stage 1997Survival Clinical Stage

• 5,319 patients– 4351 MD Anderson– 968 LCSG

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

JTCVS 1978;76:832-39

Tsuguo Naruke, MD

Mountain Dresler Lymph Node Map

Level 4R superior

Level 4R inferior

Level 12R

Level 10R

Level 11R

Level 2R Level 2L

Level 4L

Level 10L

Level 8L

Level 9L

Chest 1997;111:17178-23

• No change in descriptors

• Zones consisting of multiple levels correlate with survival

• ? Define N by zone or combination of zones

J Thorac Oncol 2007;2:603-12

Revisions of the N Descriptor

Hilar zone

Lower zone

Upper zone (R)

AP Zone (L)

Peripheral zone

Subcarinal zone

• 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 M Descriptor

• 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

Revisions of the Stage Groupings

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