The IASLC Lung Cancer Staging Project: Articles Regarding the 8th Edition of the TNM ...

242 Pages·2017·33.5 MB·English

The IASLC Lung Cancer Staging Project:
Articles Regarding the 8th Edition of the TNM Classification for
Lung Cancer, Thymic Tumours, and Mesothelioma
Contents | Page # Contents | Page #
Introduction ....................................................................................................................................2 Part 3: Summary of Methodology and Validation
Preface ...............................................................................................................................................3 12. Detterbeck F, Groome P, Bolejack V, et al. The IASLC Lung Cancer
Staging Project: methodology and validation used in the
Section I. 8th Edition of the TNM Classification of Lung Cancer
development of proposals for revision if the stage classification
Part 1: Original Articles to Inform the 8th EdCitoionnq ouf ethrein g Thoracic Canceorfs n Wono-srmldawll cidelel lung cancer in the forthcoming (eighth) edition
TNM Classification of Lung Cancer of the TNM classification of lung cancer. J Thorac Oncol.
2016;11:1433-1446 .....................................................................................................145
1. Rami-Porta R, Bolejack V, Giroux DJ, et al. The IASLC lung cancer
staging project: the new database to inform the eighth edition of Section II. 8th Edition of the TNM Classification for Epithelial
the TNM classification of lung cancer. J Thorac Oncol. 2014; 9: Thymic Tumours
1618-1624. .............................................................................................................................5
13. Detterbeck F, Asamura H, Crowley J, et al. The IASLC/ITMIG
2. Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC lung cancer Thymic Malignancies Staging Project: Development of a Stage
staging project: proposals for the revisions of the T descriptors in Classification for Thymic Malignancies. J Thorac Oncol. 2013
the forthcoming 8th edition of the TNM classification for lung Dec;8:1467-1473. .........................................................................................................160
cancer. J Thorac Oncol. 2015; 10: 990-1003 .....................................................12
14. Detterbeck F, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic
3. Asamura H, Chansky K, Crowley J, et al. The IASLC lung cancer Epithelial Tumors Staging Project: Proposal for an Evidence-Based
staging project: proposals for the revisions of the N descriptors Stage Classification System for the Forthcoming (8th) Edition
in the forthcoming 8th edition of the TNM classification for lung of the TNM Classification of Malignant Tumors. J Thorac Oncol.
cancer. J Thorac Oncol. 2015; 10: 1675-1684 ...................................................26 2014;9:S65-S72 (9 Suppl 2). ...................................................................................167
4. Eberhardt WEE, Mitchell A, Crowley J, et al. The IASLC lung cancer 15. Nicholson AG, Detterbeck F, Marino M, et al. The IASLC/ITMIG
staging project: proposals for the revisions of the M descriptors Thymic Epithelial Tumors Staging Project: Proposals for the
in the forthcoming 8th edition of the TNM classification for lung T component for the Forthcoming (8th) Edition of the TNM
cancer. J Thorac Oncol. 2015; 10: 1515-1522 ...................................................36 Classification of Malignant Tumors. J Thorac Oncol. 2014; 9:
Articles Regarding the 8thS7 3E–S8d0....i...t....i....o........n....... ....o........f.... .... ............................................................................175
5. Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer
staging project: proposals for the revision of the stage grouping 16. Kondo K, Schil P, Detterbeck F, et al. The IASLC/ITMIG Thymic
in the forthtcohmieng (8TthN) edMition ofC thel TaNMs clsassiifificatciona oft luinog n for EpLithuelianl Tugmo rsC Staaginng Pcrojeectr: P,r oposals for the N and M
cancer. J Thorac Oncol. 2016; 11: 39-51 ..............................................................44 Components for the Forthcoming (8th) Edition of the TNM
Classification of Malignant Tumors. J Thorac Oncol.
6. Nicholson TAGh, Chyanmsky Ki, cCro wTleuy Jm, et alo. Thue IArSsLC ,lu nag canncder Mes2o01t4;h9S8e1-Sl8i7 o(9 Smuppla 2) .....................................................................................183
staging project: proposals for the revision of the clinical and
pathologic staging of small cell lung cancer in the forthcoming 17. Bhora F, Chen D, Detterbeck F, et al. The ITMIG/IASLC Thymic
eighth edition of the TNM classification for lung cancer. J Thorac Epithelial Tumors Staging Project: A Proposed Lymph Node Map
Oncol. 2015; 11:300-311 ..............................................................................................57 for Thymic Epithelial Tumors in the Forthcoming 8th Edition
of the TNM Classification of Malignant Tumors. J Thorac Oncol.
Part 2: Articles with Additional Recommendations for 2014;9:S88-S96. (9 Suppl 2) ....................................................................................190
Uniform Classification
Section III. 8th Edition of the TNM Classification for Malignant
7. Travis WD, Asamura H, Bankier A, et al. The IASLC Lung Cancer Pleural Mesothelioma
Staging Project: Proposals for Coding T Categories for Subsolid
Nodules and Assessment of Tumor Size in Part-Solid Tumors in 18. Pass H, Giroux D, KeSnnTeAdGy EC, et aTl. The IASLC MNesotheliomaM
the Forthcoming Eighth Edition of the TNM Classification of Lung Staging Project: Improving Staging of a Rare Disease Through
Cancer. J Thorac Oncol. 2016 Aug;11:1204-1223 ..........................................70 International ParticipIation. J ThorTac1 Oncol. 201N6;0 dx.doi.org/M 0
10.1016/j.jtho.2016.09.123 (in press) ................................................................200
8. Detterbeck FC, Nicholson AG, Franklin WA, et al. The IASLC Lung II T2 N0 M0
Cancer Staging Project: proposals for revisions of the classification 19. Nowak A, Chansky K, Rice D, et al. The IASLC Mesothelioma
of lung cancers with multiple pulmonary sites of involvement in Staging Project: PropIIoIAsals for RevTis3ions of the NT 0DescriptorsM in0 the
the forthcoming eighth edition of the TNM classification. Forthcoming EighthI IEIBdition of thTe4 TNM ClassiNfic0ation for PlMeu0ral
J Thorac Oncol. 2016;11:639-650 ............................................................................90 Mesothelioma. J Thorac Oncol. 2016; dx.doi.org/10.1016/
j.jtho.2016.08.147 (inIV pAress) .............A....n...y... ..T..................N....1.........................M......0......207
9. Detterbeck FC, Franklin WA, Nicholson AG et al. The IASLC Lung
Cancer Staging Project: Background data and proposed criteria 20. Rusch V, Chansky K, Kindler H, et Aaln. Tyh Te IASLC NM0es,1otheliomMa 1a
to distinguish separate primary lung cancers from metastatic foci Staging Project: PropIVoBsals for theA Mn yD eTscriptoNrs2 and for RevMisi0o,n1 a
in patients with two lung tumors in the forthcoming eighth of the TNM Stage Groupings in the Forthcoming (Eighth) Edition
edition of the TNM classification for lung cancer. J Thorac Oncol. of the TNM Classification for MesAotnhye lTioma. J TAhnoyra Nc Oncol.M 2011b6;
2016;11:651-665. ...........................................................................................................102 dx.doi.org/10.1016/j.jtho.2016.09.124 (in press) .......................................218
10. Detterbeck FC, Bolejack V, Arenberg DA, et al. The IASLC Lung 21. Rice D, Chansky K, Nowak A, et al. The IASLC Mesothelioma
Cancer Staging Project: proposals for the classification of lung Staging Project: Proposals for Revisions of the N Descriptors in the
cancer with separate tumor nodules in the forthcoming eighth Forthcoming Eighth Edition of the TNM Classification for Pleural
edition of the TNM classification for lung cancer. J Thorac Oncol. Mesothelioma. J Thorac Oncol. 2016; 10.1016/j.jtho.2016.09.121
2016; 11:681-692 ..........................................................................................................117 (in press).............................................................................................................................225
11. Detterbeck FC, Marom EM, Arenberg DA, et al. The IASLC Lung
Cancer Staging Project: proposals for the application of TNM
staging rules to lung cancer presenting as multiple nodules
with ground glass or lepidic features or a pneumonic-type of
involvement in the forthcoming eighth edition of the TNM
classification. J Thorac Oncol. 2016;11:666-680 ..........................................129
1
The IASLC Lung Cancer Staging Project:
Articles Regarding the 8th Edition of the TNM Classification for
Lung Cancer, Thymic Tumours, and Mesothelioma
Contents | Page # Contents | Page #
Introduction ....................................................................................................................................2 Part 3: Summary of Methodology and Validation
Preface ...............................................................................................................................................3 12. Detterbeck F, Groome P, Bolejack V, et al. The IASLC Lung Cancer
Staging Project: methodology and validation used in the
Section I. 8th Edition of the TNM Classification of Lung Cancer
development of proposals for revision if the stage classification
Part 1: Original Articles to Inform the 8th Edition of the of non-small cell lung cancer in the forthcoming (eighth) edition
TNM Classification of Lung Cancer of the TNM classification of lung cancer. J Thorac Oncol.
2016;11:1433-1446 .....................................................................................................145
1. Rami-Porta R, Bolejack V, Giroux DJ, et al. The IASLC lung cancer
staging project: the new database to inform the eighth edition of Section II. 8th Edition of the TNM Classification for Epithelial
the TNM classification of lung cancer. J Thorac Oncol. 2014; 9: Thymic Tumours
1618-1624. .............................................................................................................................5
13. Detterbeck F, Asamura H, Crowley J, et al. The IASLC/ITMIG
2. Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC lung cancer Thymic Malignancies Staging Project: Development of a Stage
staging project: proposals for the revisions of the T descriptors in Classification for Thymic Malignancies. J Thorac Oncol. 2013
the forthcoming 8th edition of the TNM classification for lung Dec;8:1467-1473. .........................................................................................................160
cancer. J Thorac Oncol. 2015; 10: 990-1003 .....................................................12
14. Detterbeck F, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic
3. Asamura H, Chansky K, Crowley J, et al. The IASLC lung cancer Epithelial Tumors Staging Project: Proposal for an Evidence-Based
staging project: proposals for the revisions of the N descriptors Stage Classification System for the Forthcoming (8th) Edition
in the forthcoming 8th edition of the TNM classification for lung of the TNM Classification of Malignant Tumors. J Thorac Oncol.
cancer. J Thorac Oncol. 2015; 10: 1675-1684 ...................................................26 2014;9:S65-S72 (9 Suppl 2). ...................................................................................167
4. Eberhardt WEE, Mitchell A, Crowley J, et al. The IASLC lung cancer 15. Nicholson AG, Detterbeck F, Marino M, et al. The IASLC/ITMIG
staging project: proposals for the revisions of the M descriptors Thymic Epithelial Tumors Staging Project: Proposals for the
in the forthcoming 8th edition of the TNM classification for lung T component for the Forthcoming (8th) Edition of the TNM
cancer. J Thorac Oncol. 2015; 10: 1515-1522 ...................................................36 Classification of Malignant Tumors. J Thorac Oncol. 2014; 9:
S73–S80..............................................................................................................................175
5. Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer
staging project: proposals for the revision of the stage grouping 16. Kondo K, Schil P, Detterbeck F, et al. The IASLC/ITMIG Thymic
in the forthcoming (8th) edition of the TNM classification of lung Epithelial Tumors Staging Project: Proposals for the N and M
cancer. J Thorac Oncol. 2016; 11: 39-51 ..............................................................44 Components for the Forthcoming (8th) Edition of the TNM
Classification of Malignant Tumors. J Thorac Oncol.
6. Nicholson AG, Chansky K, Crowley J, et al. The IASLC lung cancer 2014;9S81-S87 (9 Suppl 2) .....................................................................................183
staging project: proposals for the revision of the clinical and
pathologic staging of small cell lung cancer in the forthcoming 17. Bhora F, Chen D, Detterbeck F, et al. The ITMIG/IASLC Thymic
eighth edition of the TNM classification for lung cancer. J Thorac Epithelial Tumors Staging Project: A Proposed Lymph Node Map
Oncol. 2015; 11:300-311 ..............................................................................................57 for Thymic Epithelial Tumors in the Forthcoming 8th Edition
of the TNM Classification of Malignant Tumors. J Thorac Oncol.
Part 2: Articles with Additional Recommendations for 2014;9:S88-S96. (9 Suppl 2) ....................................................................................190
Uniform Classification
Section III. 8th Edition of the TNM Classification for Malignant
7. Travis WD, Asamura H, Bankier A, et al. The IASLC Lung Cancer Pleural Mesothelioma
Staging Project: Proposals for Coding T Categories for Subsolid
Nodules and Assessment of Tumor Size in Part-Solid Tumors in 18. Pass H, Giroux D, Kennedy C, et al. The IASLC Mesothelioma
the Forthcoming Eighth Edition of the TNM Classification of Lung Staging Project: Improving Staging of a Rare Disease Through
Cancer. J Thorac Oncol. 2016 Aug;11:1204-1223 ..........................................70 International Participation. J Thorac Oncol. 2016; dx.doi.org/
10.1016/j.jtho.2016.09.123 (in press) ................................................................200
8. Detterbeck FC, Nicholson AG, Franklin WA, et al. The IASLC Lung
Cancer Staging Project: proposals for revisions of the classification 19. Nowak A, Chansky K, Rice D, et al. The IASLC Mesothelioma
of lung cancers with multiple pulmonary sites of involvement in Staging Project: Proposals for Revisions of the T Descriptors in the
the forthcoming eighth edition of the TNM classification. Forthcoming Eighth Edition of the TNM Classification for Pleural
J Thorac Oncol. 2016;11:639-650 ............................................................................90 Mesothelioma. J Thorac Oncol. 2016; dx.doi.org/10.1016/
j.jtho.2016.08.147 (in press) ....................................................................................207
9. Detterbeck FC, Franklin WA, Nicholson AG et al. The IASLC Lung
Cancer Staging Project: Background data and proposed criteria 20. Rusch V, Chansky K, Kindler H, et al. The IASLC Mesothelioma
to distinguish separate primary lung cancers from metastatic foci Staging Project: Proposals for the M Descriptors and for Revision
in patients with two lung tumors in the forthcoming eighth of the TNM Stage Groupings in the Forthcoming (Eighth) Edition
edition of the TNM classification for lung cancer. J Thorac Oncol. of the TNM Classification for Mesothelioma. J Thorac Oncol. 2016;
2016;11:651-665. ...........................................................................................................102 dx.doi.org/10.1016/j.jtho.2016.09.124 (in press) .......................................218
10. Detterbeck FC, Bolejack V, Arenberg DA, et al. The IASLC Lung 21. Rice D, Chansky K, Nowak A, et al. The IASLC Mesothelioma
Cancer Staging Project: proposals for the classification of lung Staging Project: Proposals for Revisions of the N Descriptors in the
cancer with separate tumor nodules in the forthcoming eighth Forthcoming Eighth Edition of the TNM Classification for Pleural
edition of the TNM classification for lung cancer. J Thorac Oncol. Mesothelioma. J Thorac Oncol. 2016; 10.1016/j.jtho.2016.09.121
2016; 11:681-692 ..........................................................................................................117 (in press).............................................................................................................................225
11. Detterbeck FC, Marom EM, Arenberg DA, et al. The IASLC Lung
Cancer Staging Project: proposals for the application of TNM
staging rules to lung cancer presenting as multiple nodules
with ground glass or lepidic features or a pneumonic-type of
involvement in the forthcoming eighth edition of the TNM
classification. J Thorac Oncol. 2016;11:666-680 ..........................................129
1
INTRODUCTION TO STAGING PUBLICATION
A well-validated staging system and accurate staging of patients with lung cancer and other thoracic malignancies
is important for making treatment decisions. The UICC/IASLC Staging Classification is used all over the world
and the IASLC is proud to launch the 8th Edition of the International Staging of Thoracic Malignancies. While
the previous 7th Edition of the staging system was focusing on lung cancer, the new 8th Edition also includes
staging of thymic cancers and mesotheliomas. The new staging system is based on about 100,000 cases collected by
international multidisciplinary investigators from all geographic regions of the world.
This staging project has been performed by the IASLC Staging Committee under the leadership of Dr. Ramón
Rami-Porta, MD, Spain. This project could not be performed without the generous unrestricted support from
Lilly Oncology, USA.
It is our hope that the 8th Edition of the Staging Classification will be a useful tool for the optimum management
of patients with lung cancer around the world, and as a basis for further research.
David P. Carbone, MD, PhD Fred R. Hirsch, MD, PhD
President IASLC Chief Executive Director, IASLC
2
PREFACE
Ramón Rami-Porta, MD, Chair, Hisao Asamura, MD, Chair-Elect, and Peter Goldstraw, MBChB, FRCS, Past-Chair,
IASLC Staging and Prognostic Factors Committee.
The collection of original articles that you have in your hands is the result of an international and multidisciplinary
effort led by the International Association for the Study of Lung Cancer (IASLC). The IASLC Staging Project,
conceived twenty years ago, culminates its second phase with the publication of data-based recommendations for
changes to the 8th edition of the tumor, node and metastasis (TNM) classification of lung cancer and mesothelioma,
and with the promulgation, for the first time in the history of the anatomic staging system of malignant tumors, of
an internationally agreed and data-based TNM classification of thymic tumors.
These original articles, published from 2014 to 2016, provide background and detailed information on the databases
analyzed for the revision of the TNM classifications, the methodology used, and the findings that led to the
recommendations for changes. This bound volume is meant to be a companion of the second edition of the IASLC
Staging Manual in Thoracic Oncology and the IASLC Staging Handbook in Thoracic Oncology, that contain the basic
information and some additional material on the 8th edition of the TNM classification of thoracic malignancies.
Those interested in knowing in more depth the rationale for the periodical revision of the classifications will find in
this volume all the necessary scientific information.
For the second consecutive time, the IASLC has been in charge to provide the Union for International Cancer
Control (UICC) and the American Joint Committee on Cancer (AJCC) with data-based recommendations to revise
the TNM classification of thoracic malignancies. Both institutions have accepted the IASLC recommendations and
incorporated them in their respective 8th edition staging manuals that will be published in 2016. The IASLC is
grateful to our sponsors who have allowed us to fund this expanding commitment, and to the Institutions which
have generously donated their data for this effort. The IASLC is proud to serve the international oncological
community and thanks the UICC and the AJCC for entrusting it with such challenging and intellectually rewarding
responsibility.
3
Section I. 8th Edition of the TNM Classification of Lung Cancer
Part 1: Original Articles to Inform the 8th Edition of
the TNM Classification of Lung Cancer
4
IASLC S C a
tagIng ommIttee rtICle
The IASLC Lung Cancer Staging Project: The New Database 
to Inform the Eighth Edition of the TNM Classification of 
Lung Cancer
Ramón Rami-Porta, MD, FETCS,*† Vanessa Bolejack, MPH,‡ Dorothy J. Giroux, MS,‡
Kari Chansky, MS,‡ John Crowley, PhD,‡ Hisao Asamura, MD,§ Peter Goldstraw, MBChB, FRCS,║
on behalf of the International Association for the Study of Lung Cancer Staging and Prognostic Factors
Committee, Advisory Board Members and Participating Institutions¶
Key Words: Lung cancer, Lung cancer databases, Lung cancer
Abstract: The analyses of the retrospective database of the
staging, Nonsmall cell lung cancer, Small cell lung cancer, TNM
International Association for the Study of Lung Cancer (IASLC),
classification.
consisting of more than 81,000 evaluable patients diagnosed with
lung cancer between 1990 and 2000, formed the basis of recom- (J Thorac Oncol. 2014;9: 1618–1624)
mendations to the Union for International Cancer Control and the
American Joint Committee on Cancer for the revision of the sixth
edition of the tumor, node, and metastasis (TNM) classification of The call for action launched during the International
lung cancer. However, despite the large number of patients, not all Workshop on Intrathoracic Staging, that took place in
descriptors could be validated. This prompted a new collection of London, United Kingdom, in October 19961 to revise and
retrospective and prospective data to overcome the limitations of the improve the tumor, node, and metastasis (TNM) classification
original retrospective database. The new IASLC database has infor- of lung cancer, resulted in an unprecedented response from
mation on 94,708 new patients diagnosed of lung cancer between groups and institutions around the world. By 2005, data on
1999 and 2010. They originated from 35 sources in 16 countries, and 100,869 patients diagnosed of lung cancer between 1990 and
4,667 were submitted via the online electronic data capture system. 2000 were submitted to the International Association for the
Europe contributed 46,560 patients, Asia: 41,705, North America: Study of Lung Cancer (IASLC) database at Cancer Research
4,660, Australia: 1,593, and South America: 190. After exclusions,
And Biostatistics (CRAB). These data originated from 46
77,156 (70,967 with nonsmall cell lung cancer and 6,189 with small
different sources in 20 countries of Europe, North America,
cell lung cancer) remained for analysis. This database will be ana-
Asia, and Australia. After exclusions, 81,495 patients were
lyzed according to established objectives for the T, the N, and the M
available for analyses: 68,463 with nonsmall cell lung cancer
components to inform the eighth edition of the TNM classification
(NSCLC) and 13,032 with small cell lung cancer (SCLC).2
of lung cancer due to be published in 2016. The IASLC hopes for the
From the analyses of these data, a series of research articles
continuing contribution of our partners around the world to improve
on the T,3 the N,4 and the M5 components of the TNM clas-
the classification of anatomical extent of disease, but also to create
sification were peer-reviewed and published in the Journal of
prognostic groups in a parallel project of the IASLC Staging and
Thoracic Oncology for public discussion. In a similar manner,
Prognostic Factors Committee.
a revised stage grouping was proposed,6 the new findings were
internally and externally validated,7 and the TNM classifica-
tion was tested and validated for SCLC8,9 and, for the first time
*Department of Thoracic Surgery, Hospital Universitari Mutua Terrassa, in the history of the anatomical staging of malignant tumors,
University of Barcelona; †CIBERES Lung Cancer Group, Terrassa, for broncho-pulmonary carcinoids.10 In addition, a new lymph
Barcelona, Spain; ‡Cancer Research And Biostatistics, Seattle, WA;
node map, resulting from an international and multidisci-
§Department of Thoracic Surgery, National Cancer Center Hospital,
Tokyo, Japan; and ║Department of Thoracic Surgery, Royal Brompton plinary consensus and reconciling the differences of the pre-
Hospital and Imperial College, London, United Kingdom; ¶Members vious ones, was proposed for prospective validation;11 and a
of the Staging and Prognostic Factors Committee are listed in the new definition of visceral pleura invasion was agreed based on
Appendix 1.
the published data.12 The nonanatomic information included
Disclosure: The authors declare no conflict of interest.
Address for correspondence: Ramón Rami-Porta, MD, FETCS, Department in the database was used to create prognostic groups before
of Thoracic Surgery, Hospital Universitari Mutua Terrassa, Plaza Dr. and after surgical treatment based on the combination of ana-
Robert 5, 08221 Terrassa, Barcelona, Spain. E-mail: [email protected] tomic staging and very simple clinical variables, such as age,
DOI: 10.1097/JTO.0000000000000334
gender, and performance status.13,14 The recommendations for
Copyright © 2014 by the International Association for the Study of Lung
changes in the TNM classification of lung cancer derived from
Cancer
ISSN: 1556-0864/14/0911-1618 the analyses of the IASLC database (Table 1) were submitted
Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014
5
Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014 IASLC Lung Cancer Staging Project
to the Union for International Cancer Control (UICC) and
TABLE 2.  Number of Cases Submitted by Each Data Source, 
the American Joint Committee on Cancer (AJCC), and were
by Continent
accepted and subsequently published in the seventh edition of
their staging manuals.15,16 At the same time, the IASLC pro- Region Data Source EDC Source N
duced the Staging Handbook in Thoracic Oncology and the Asia EDC Guangdong General Hospital, China 739
Staging Manual in Thoracic Oncology including the TNM Shanghai Lung Tumor Clinical 51
classifications of lung cancer and mesothelioma, the general Medical Center, China
rules of the TNM classification, site-specific rules for lung Japan 1999 13,344
cancer and mesothelioma, and complementary chapters on Japan 2002 14,695
survival analyses, prognostic factors, frequently asked ques- Japan 2004 10,889
tions and the history of the TNM classification since its incep-
South Korea 1,987
tion by Pierre Denoix in the mid 20th century.17,18 With this
Australia EDC Peter MacCallum Cancer Centre 4
contribution, the IASLC became the primary source of data-
Prince 229
based evidence to revise subsequent editions of the UICC and Charles
the AJCC TNM classifications of thoracic malignancies.
Sydney 1,360
Despite the vastness of the IASLC database, not all
Europe Belgrade, 88
descriptors of the T, the N, and the M components of the ana- Serbia
tomical classification could be validated. The main reason was Denmark 33,949
that many of the original datasets of the contributing databases
EDC Athens School of Medicine, Greece 39
had not been designed to study the TNM classification. The
Clinical Center of Serbia, Serbia 40
resulting lack of detailed data prevented the analyses of many
GCCB-S, Spain 2,362
descriptors. For the T component, only could tumor size, addi-
L’Institut Mutualiste 120
tional tumor nodule(s) and pleural effusion be analyzed reli-
Montsouris, France
ably. For the N component, the present categories could be
Military Medical Academy, Serbia 20
validated in the clinical and pathological staging. However, the
Antwerp University Hospital, 195
Multidisciplinary Oncological
Centre Antwerp (MOCA), Belgium
TABLE 1.  Innovations Introduced in the seventh Edition  University Hospital Ghent, Belgium 85
of the Tumor, Node, and Metastases Classification of Lung  University of Torino, Italy 4
Cancer Norway 2,354
Turkey 7,304
Category/Stage in Category/Stage in
Descriptor/TNM the sixth Edition the seventh Edition North and EDC Alexander Fleming Institute, Argentina 6
South Clinica y Maternidad Suizo Argentina, 3
Tumor size ≤ 2 cm T1 T1a America Argentina
Tumor size > 2 cm T1 T1b
Fundación Clínica 2
but ≤ 3 cm
Valle del Lili, Colombia
Tumor size > 3 cm T2 T2a
Good Samaritan Hospital, USA 10
but ≤ 5 cm
Hospital Británico de Buenos Aires, 68
Tumor size > 5 cm T2 T2b
Argentina
but ≤ 7 cm
Hospital Universitario Austral, 46
Tumor size > 7 cm T2 T3
Argentina
Additional tumor nodule(s) T4 T3
Hospital Universitario-Fundación 36
in the same lobe of the
Favaloro, Argentina
primary tumor
Hospital de Rehabilitación 14
Additional tumor nodule(s) M1 T4
Respiratoria, Argentina
in another ipsilateral lobe
Mayo Clinic Rochester, USA 47
Pleural dissemination T4 M1a
(malignant pleural New York University Langone Medical 688
effusion and separated Center and Cancer Center, USA
pleural nodules) Penrose Cancer Center, USA 73
Pericardial dissemination N/A M1a University of Sao Paulo Medical 15
(malignant pericardial School, Brazil
effusion
MDACC, 2,415
and separated pericardial
USA
nodules)
MSKCC, 1,427
Intrathoracic metastases M1 M1a
USA
Extrathoracic metastases M1 M1b
Global Total 94,708
T2b N0 M0 IB IIA
GCCB-S, Grupo Cooperativo de Carcinoma Broncogénico de la Sociedad Española
T2a N1 M0 IIB IIA
de Neumología y Cirugía Torácica; NYU, New York University; MDACC, M. D.
T4 N0-1 M0 IIIB IIIA Anderson Cancer Center; MSKCC, Memorial Sloan-Kettering Cancer Center.
Copyright © 2014 by the International Association for the Study of Lung Cancer
6
Rami-Porta et al. Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014
TABLE 3.  Number of Cases Submitted to the Database,  TABLE 5.  Comparison of Basic Elements of the Two IASLC 
With Exclusions and the Numbers Remaining for Analysis Databases Used for Informing the seventh Edition and the 
eighth Edition of the TNM Classification of Lung Cancer
Submitted 94,708
Excluded 17,552 Element Database for the Database for the
seventh Edition eighth Edition
Carcinoids 745
Other or unknown histology 5,986 Period of diagnosis 1990 to 2000 1999 to 2010
Outside 1999–2010 timeframe 525 Total patients submitted 100,869 94,708
Incomplete survival data 938 Geographical origin
Incomplete stage information 9,286 Europe 58,701 (58%) 46,560 (49%)
Multiple synchronous tumors 72 North America 21,130 (21%) 4,660 (5%)
Included in initial analyses 77,156 Asia 11,622 (11.5%) 41,705 (44%)
NSCLC 70,967 Australia 9,416 (9.3%) 1,593 (1.7%)
SCLC 6,189 South America 0 190 (0.3%)
Patients excluded 19,374 (19%) 17,552 (18%)
Patients included for 81,495 77,154
TABLE 4.  Number of Cases Analyzed by Type of Data  analyses
Source NSCLC 68,463 (84%) 70,967 (92%)
SCLC 13,032 (16%) 6,189 (8%)
Other EDC Total
Treatment modalities
Data source type
Surgery alone 41% 57.7%
Consortium 41,548 2,089 43,637
Radiotherapy + surgery 5% 1.5%
Registry 26,122 26,122
Chemotherapy + surgery 4% 21.1%
Surgical series 5,373 592 5,965
Chemotherapy alone 23% 9.3%
Institutional series 1,185 1,185
Radiotherapy alone 11% 1.5%
Institutional registry 208 208
Chemotherapy + 12% 4.7%
Unknown 39 39 radiotherapy
Total 73,251 3,905 77,156 Trimodality 3% 4.4%
Consortium: group of institutions where all individuals diagnosed with lung cancer
are registered. Registry: all individuals diagnosed with lung cancer in a defined region,
including those diagnosed at death. Surgical series: all individuals diagnosed with data online and retrieve their own data for their own stud-
lung cancer and treated by a particular surgeon or unit. Institutional series: same as
ies at any time. Europe contributed 46,560 patients, Asia:
consortium, but in a single institution; may be limited to a specific treatment specialty
or specialties. Institutional registry: all individuals diagnosed with lung cancer and 41,705, North America: 4,660, Australia: 1,593, and South
admitted to a particular institution are registered. America: 190. These new data came from 35 sources in 16
countries (Table 2). After excluding 17,552 patients, mainly
because of unknown or different histology and incomplete
new information on the prognostic impact of nodal tumor bur-
stage information, 77,156 patients (70,967 with NSCLC
den represented by the number of involved nodal zones found
and 6,189 with SCLC) remained for analyses (Table 3). The
at pathological staging could not be used to modify the N cat-
majority of these patients (99%) had been collected by con-
egories because it could not be validated at clinical staging, by
sortia or registries. There were no patients from clinical tri-
geographical regions or by the different T categories. Finally,
als (Table 4). Nearly 85% of the patients underwent surgical
in the M component, although there was enough information
treatment either alone or in combination with chemotherapy
to separate intrathoracic from extrathoracic metastases, noth-
or radiotherapy (Table 5). This is reflected in the stage dis-
ing could be said about the prognostic impact of number and
tribution of NSCLC: except in Europe, where there is pre-
site of metastases.19 These limitations prompted the IASLC
dominance of advanced stages, early stages are predominant,
Staging and Prognostic Factors Committee to launch a second
especially in Asia; for SCLC, advanced stages are predomi-
phase of its Lung Cancer Staging Project with the objective to
nant, as expected (Figure 1).
overcome the limitations of the initial project,20 and to restruc-
This new database is being analyzed according to con-
ture its membership (Appendix 2).
crete objectives for each of the T, the N, and the M compo-
nents of the classification. In essence, the principal aims are to
THE NEW IASLC DATABASE further explore and analyze the impact on prognosis of tumor
The new database, the analyses of which will inform size and of the different T descriptors; the prognostic signifi-
the eighth edition of the TNM classification of lung cancer, cance of tumor burden in hilar and mediastinal lymph nodes;
consists of 94,708 patients diagnosed from 1999 to 2010. and the confirmation of the revised M1 categories (M1a and
Their data originated from established databases (90,041 M1b) of the seventh edition of the classification along with
patients) or were submitted via the electronic data capture the prognostic impact of number and anatomic location of
(EDC) system set by Cancer Research And Biostatistics metastases.20 For this phase of the study, in addition to the
(4,667 patients). The EDC allows the contributors to submit data elements collected in the initial phase,2 the descriptors
Copyright © 2014 by the International Association for the Study of Lung Cancer
7
Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014 IASLC Lung Cancer Staging Project
TABLE 6.  Nonanatomical Elements Collected in the New 
Phase of the IASLC Lung Cancer Staging Project
Patient-related Age
elements Sex
Race
Smoking history
Weight loss
Zubrod performance status
Comorbidity index
Laboratory analyses: LDH, hemoglobin, calcium,
alkaline phosphatase, sodium, leukocyte count,
neutrophil count, platelets, albumin
Lung function tests: FVC and % of predicted;
FEV1 and % of predicted
Weight
Height
Tumor-related SUVmax for T and for N
elements Lobar, bronchial location of primary tumor
Differentiation grade
Histological type
Vascular invasion
Lymphatic invasion
Pleural lavage cytology
Tumor markers in those centers that have
the possibility to determine them
Environment-related Method of detection: symptoms,
elements screening, incidental
Treatment
Residual tumor after treatment
Geographic area: continent, country of origin
LDH: lactate-dehydrogenase; FVC: forced vital capacity; FEV1: forced expiratory
volume in 1 second; SUVmax: maximum standardized uptake value; T: primary tumor;
N: lymph nodes
enhances the capacity to prognosticate beyond that of the
TNM classification alone. These combined prognostic indexes
will help personalize prognosis for a given patient.
The new database is almost as large as the one used for
the seventh edition. As a matter of fact, some of the already
established databases that have been submitted were not spe-
cifically designed to study the TNM classification and have the
same limitations as the original IASLC database. However,
the data contributed via the EDC contained all the necessary
elements to do so. Although smaller in number of patients, it
is much richer in details to allow refinements in the analyses
of the different descriptors. Europe still is the leading contrib-
uting region, closely followed by Asia, thanks to the massive
FIGURE 1.  Histograms of stage (pathological stage, if  participation of Japan. In relation to the previous database, the
provided; otherwise, clinical stage) distribution by region. (A)  cases from North America and Australia have dropped; and
Nonsmall cell lung cancer; (B) small cell lung cancer; and (C)  South America is represented by a few cases for the first time.
overall.
Patients undergoing surgical treatment alone are predominant,
as in the previous database. Owing to the nature of the data
of the TNM classification were collected according to its sources (no clinical trials), the number of patients treated with
seventh edition. Moreover, 23 nonanatomical elements were chemotherapy alone or in combination with radiotherapy has
included in the data dictionary to prepare for the development dropped. This database contains a similar number of patients
of prognostic groups (Table 6). The combination of anatomic with NSCLC, but the number of patients with SCLC has been
and nonanatomic elements in a combined prognostic index reduced by 50% (Table 5).
Copyright © 2014 by the International Association for the Study of Lung Cancer
8
Rami-Porta et al. Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014
The analyses of the new database and the findings sug- Argentina; Mirella Marino, Regina Elena National Cancer
gesting recommendations for the revision of the seventh edi- Institute, Rome, Italy; Edith M. Marom, MD Anderson Cancer
tion of the TNM classification of lung cancer will be submitted Center, Houston, TX, USA; Jan van Meerbeeck, Antwerp
to the Journal of Thoracic Oncology to make them available University Hospital, Edegem (Antwerp), Belgium; Alan
to the worldwide oncology community. The suggested recom- Mitchell, Cancer Research And Biostatistics, Seattle, WA,
mendations and their supportive data will also be submitted USA; Takashi Nakano, Hyogo College of Medicine, Hyogo,
to the UICC and the AJCC for their assessment and inclusion Japan; Andrew G. Nicholson, Royal Brompton and Harefield
in their new staging manuals, due to be published in 2016. NHS Foundation Trust and Imperial College, London, United
The new edition of the classification will then be enacted in Kingdom; Anna Nowak, University of Western Australia,
January 2017. Perth, Australia; Michael Peake, Glenfield Hospital, Leicester,
The contributing institutions are to be thanked for their United Kingdom; Thomas Rice, Cleveland Clinic, Cleveland,
touching generosity and enthusiasm. This is an ongoing proj- OH, USA; Kenneth Rosenzweig, Mount Sinai Hospital, New
ect that will soon be complemented by a deeper study on York, NY, USA; Enrico Ruffini, University of Torino, Torino,
prognostic factors, for which prospective data collection will Italy; Valerie Rusch, Memorial Sloan-Kettering Cancer
be essential. We hope that this new project will be appeal- Center, New York, NY, USA; Nagahiro Saijo, National
ing to the international lung cancer community and will be Cancer Center Hospital East, Chiba, Japan; Paul Van Schil,
supported again by our regular contributors and, hopefully, by Antwerp University Hospital, Edegem (Antwerp), Belgium;
new ones. Although there are several ways to contribute,21 the Jean-Paul Sculier, Institut Jules Bordet, Brussels, Belgium;
best way to serve the objectives of the IASLC Lung Cancer Lynn Shemanski, Cancer Research And Biostatistics, Seattle,
Staging Project is to submit cases via the EDC. The online WA, USA; Kelly Stratton, Cancer Research And Biostatistics,
dataset contains the specific data elements needed to study the Seattle, WA, USA; Kenji Suzuki, Juntendo University, Tokyo,
descriptors of the three components of the TNM classifica- Japan; Yuji Tachimori, National Cancer Center, Tokyo, Japan;
tion and to refine prognosis. Your collaboration will be much Charles F. Thomas Jr, Mayo Clinic, Rochester, MN, USA;
welcome. William Travis, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA; Ming S. Tsao, The Princess Margaret
APPENDIX 1. IASLC Staging and Prognostic Cancer Centre, Toronto, Ontario, Canada; Andrew Turrisi,
Factors Committee Sinai Grace Hospital, Detroit, MI, USA; Johan Vansteenkiste,
Peter Goldstraw, Past Chair, Royal Brompton Hospital University Hospitals, Leuven, Belgium; Hirokazu Watanabe,
and Imperial College, London, United Kingdom; Ramón National Cancer Center Hospital, Tokyo, Japan; Yi-Long Wu,
Rami-Porta, Chair, Hospital Universitari Mutua Terrassa, Guangdong Provincial Peoples Hospital, Guangzhou, People’s
Terrassa, Spain; Hisao Asamura, Chair Elect, National Cancer Republic of China.
Center, Tokyo, Japan; David Ball, Peter MacCallum Cancer
Centre, Melbourne, Australia; David Beer, University of Advisory Board of the IASLC Mesothelioma Domain
Michigan, Ann Arbor, MI, USA; Ricardo Beyruti, University Paul Baas, The Netherlands Cancer Institute,
of Sao Paulo, Brazil; Vanessa Bolejack, Cancer Research Amsterdam, The Netherlands; Jeremy Erasmus, MD Anderson
And Biostatistics, Seattle, WA, USA; Kari Chansky, Cancer Cancer Center, Houston, TX, USA; Seiki Hasegawa, Hyogo
Research And Biostatistics, Seattle, WA, USA; John Crowley, College of Medicine, Hyogo, Japan; Kouki Inai, Hiroshima
Cancer Research And Biostatistics, Seattle, WA, USA; University Postgraduate School, Hiroshima, Japan; Kemp
Frank Detterbeck, Yale University, New Haven, CT, USA; Kernstine, City of Hope, Duarte, CA, USA; Hedy Kindler, The
Wilfried Ernst Erich Eberhardt, West German Cancer Centre, University of Chicago Medical Center, Chicago, IL, USA; Lee
University Hospital, Ruhrlandklinik, University Duisburg- Krug, Memorial Sloan-Kettering Cancer Center, New York,
Essen, Essen, Germany; John Edwards, Northern General NY, USA; Kristiaan Nackaerts, University Hospitals, Leuven,
Hospital, Sheffield, United Kingdom; Françoise Galateau- Belgium; Harvey Pass, New York University, NY, USA; David
Sallé, Centre Hospitalier Universitaire, Caen, France; Dorothy Rice, MD Anderson Cancer Center, Houston, TX, USA.
Giroux, Cancer Research And Biostatistics, Seattle, WA,
USA; Fergus Gleeson, Churchill Hospital, Oxford, United
Advisory Board of the IASLC Thymic Malignancies
Kingdom; Patti Groome, Queen’s Cancer Research Institute,
Domain
Kingston, Ontario, Canada; James Huang, Memorial Sloan-
Conrad Falkson, Queen’s University, Ontario, Canada;
Kettering Cancer Center, New York, NY, USA; Catherine
Pier Luigi Filosso, University of Torino, Italy; Giuseppe
Kennedy, University of Sydney, Sydney, Australia; Jhingook
Giaccone, Georgetown University, Washington, DC, USA;
Kim, Samsung Medical Center, Seoul, Korea; Young Tae
Kazuya Kondo, University of Tokushima, Tokushima, Japan;
Kim, Seoul National University, Seoul, South Korea; Laura
Marco Lucchi, University of Pisa, Pisa, Italy; Meinoshin
Kingsbury, Cancer Research And Biostatistics, Seattle, WA,
Okumura, Osaka University, Osaka, Japan.
USA; Haruhiko Kondo, Kyorin University Hospital, Tokyo,
Japan; Mark Krasnik, Gentofte Hospital, Copenhagen,
Denmark; Kaoru Kubota, Nippon Medical School Hospital, Advisory Board of the IASLC Esophageal Cancer
Tokyo, Japan; Antoon Lerut, University Hospitals, Leuven, Domain
Belgium; Gustavo Lyons, British Hospital, Buenos Aires, Eugene Blackstone, Cleveland Clinic, OH, USA.
Copyright © 2014 by the International Association for the Study of Lung Cancer
9