Commemorating the Silver Anniversary of the International Association for the Study of Lung Cancer International Workshop on Intrathoracic Staging

Abstract

The year 2021 marks the 25th anniversary of the International Workshop on Intrathoracic Staging that took place at the Royal Brompton Hospital, London, United Kingdom, on October 28 and 29, 1996 (Supplementary Fig. 1). Organized by Prof. Peter Goldstraw under the auspices of the International Association for the Study of Lung Cancer (IASLC), it summoned a faculty of 18 professionals from the United States of America, Japan, and Europe, especially interested in lung cancer staging, and 49 participants. Topics discussed during the Workshop included several forms of intrathoracic nodal staging, different nodal charts in use, value of pleural lavage cytology test, molecular characterization of tumors, biological markers, and pathologic examination of lymph nodes, among others (Supplementary Fig. 2). During the second afternoon of the Workshop, faculty members and participants split into two task forces to discuss specific topics, such as an international standard of intrathoracic nodal staging, a unified nodal chart, the definition of complete resection, and the revision of the staging system. Regarding the latter, Prof. Clifton Mountain, who was one of the invited speakers, was duly praised for his initiative to collect a database for the purpose of revising the TNM classification. His database of 5319 North American patients treated surgically was used to inform the second to the sixth editions of the classification, but it lacked wide geographic representation and patients treated nonsurgically. A decision was made to establish a Staging Committee in the IASLC and to create a large international database of patients from as many countries as possible treated by all therapeutic modalities with the following three main objectives: (1) to revise the TNM classification of lung cancer in light of the limitations of the North American database used until then and to begin negotiations with the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) regarding future revisions of the TNM classification of lung cancer; (2) to create an international nodal chart to uniformly classify nodal disease in lung cancer; and (3) to formulate an international and multidisciplinary definition of complete resection in lung cancer operations.1Goldstraw P. Report on the International workshop on intrathoracic staging. London, October 1996.Lung Cancer. 1997; 18: 107-111Abstract Full Text Full Text PDF Google Scholar This commentary focuses on the activities of the IASLC Staging Committee that led to the successful completion of all the objectives set 25 years ago. The IASLC Board of Directors approved the establishment of the Staging Committee in 1998. Relevant specialists to lung cancer management, including medical and radiation oncologists, pathologists, pulmonologists, radiologists, data managers, statisticians, and surgeons, were appointed as Committee members, and the Cancer Research And Biostatistics, as the agency to collect, manage, and analyze the IASLC database. Eli Lilly and Company provided funding to support the Committee’s activities, but it had no input into the data analyses or the revisions to the staging system. In the two completed phases of the Staging Project—1998 to 2009 and 2009 to 2016—the IASLC Staging Committee revised the TNM classification of lung cancer, malignant pleural mesothelioma, and epithelial thymic tumors and had an agreement with the Worldwide Esophageal Cancer Collaboration (WECC) to disseminate the TNM classification of esophageal and esophagogastric cancers together with that of the other thoracic malignancies. These revisions were based on large databases: 81,495 assessable patients with lung cancer were analyzed to inform the seventh edition of the TNM classification2Goldstraw P. Crowley J.J. The International Association for the Study of Lung Cancer international staging project on lung cancer.J Thorac Oncol. 2006; 1: 281-286Abstract Full Text Full Text PDF Scopus (0) Google Scholar and 77,156 patients with lung cancer, 2460 with malignant pleural mesothelioma and 8145 with epithelial thymic tumors, the latter registered in collaboration with the International Thymic Malignancies Interest Group, were analyzed to develop the eighth edition of their respective TNM classifications. For the same purpose, the WECC had registered 22,654 assessable patients.3Rami-Porta R. Staging Manual in Thoracic Oncology.2nd ed. Editorial Rx Press, North Fort Myers, FL2016: 28-35Google Scholar The recommendations derived from these analyses resulted in the seventh edition of the TNM classification of lung cancer, and in the eighth edition of the classification of lung cancer, malignant pleural mesothelioma, epithelial thymic tumors, and esophageal and esophagogastric juncture cancers.4Goldstraw P. Crowley J. Chansky K. et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours.J Thorac Oncol. 2007; 2: 706-714Abstract Full Text Full Text PDF PubMed Scopus (2847) Google Scholar, 5Goldstraw P. Chansky K. Crowley J. et al.The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer.J Thorac Oncol. 2016; 11: 39-51Abstract Full Text Full Text PDF PubMed Scopus (2009) Google Scholar, 6Rusch V.W. Chansky K. Kindler H.L. et al.The IASLC mesothelioma Staging Project: proposals for the M descriptors and for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for mesothelioma.J Thorac Oncol. 2016; 11: 2112-2119Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 7Detterbeck F.C. Stratton K. Giroux D. et al.The IASLC/ITMIG thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors.J Thorac Oncol. 2014; 9: S65-S72Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 8Rice T.W. Ishwaran H. Ferguson M.K. Blackstone E.H. Goldstraw P. Cancer of the esophagus and esophagogastric junction: an eighth edition staging primer.J Thorac Oncol. 2017; 12: 36-42Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar The third phase of the IASLC Staging Project (2017–2024) is now in progress and represents a big challenge. Although the TNM classification and stage grouping explain approximately 60% of the prognosis of lung cancer,5Goldstraw P. Chansky K. Crowley J. et al.The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer.J Thorac Oncol. 2016; 11: 39-51Abstract Full Text Full Text PDF PubMed Scopus (2009) Google Scholar there still is much to be improved if we want a more personalized management of individual patients. To this end, in 2013, the IASLC Board of Directors approved the change of the name of the Staging Committee, which was to be renamed IASLC Staging and Prognostic Factors Committee (SPFC). The idea behind this change was to widen the objectives of the Committee and to collect enough data not only on the anatomical extent of the tumors but also on other nonanatomical elements to build prognostic groups on the basis of their combination. To achieve this, the data set for the registration of lung cancer data includes patient-, tumor-, and environment-based prognostic factors, including molecular data, such as genetic biomarkers, copy number alterations, and protein alterations.9Giroux D.J. Van Schil P. Asamura H. et al.The IASLC Lung Cancer Staging project: a renewed call to participation.J Thorac Oncol. 2018; 13: 801-809Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Molecular characterization and the study of prognostic factors of the other thoracic malignancies are also in the agenda of the SPFC. The way in which anatomical and nonanatomical elements will be combined is still under discussion. The UICC and the AJCC have different views. Although the UICC considers staging as the result of the combination of the T, N, and M components of the purely anatomical classification, the AJCC favors the combination of both types of elements to construct what is called prognostic stage grouping. This discrepancy needs to be negotiated to avoid confusion regarding the meaning of anatomical staging and prognostic stage grouping. Other ongoing activities conducted by the members of the 17 subcommittees of the IASLC SPFC include revision of the data elements of the ninth edition to prepare for the smooth transition of data collection for the tenth edition; validation of the new T categories of lepidic adenocarcinomas; deeper study of the number, location, and volume of metastases; revision of prognostic factors of malignant pleural mesothelioma on the basis of the eighth edition data; refinement of the operative report and standardization of surgical procedures; individualized study of neuroendocrine tumors; and refinement of the residual tumor (R) descriptors. Those interested in submitting their cases will find all the necessary information (online application form, protocol document, tool kit, data use agreement form, frequently asked questions, and application for funding) in the IASLC website: www.iaslc.org >Research & Education>Research Committees & Projects>Staging and Prognostic Factors Committee>Submit Data for the ninth edition. Those cases submitted before December 31, 2021, will be included in the analyses for the ninth edition, and those submitted after that date will be incorporated in the database for the 10th edition. It took more than a decade to develop a new lymph node chart that reconciled the differences between the Naruke and the Mountain-Dresler maps used in different parts of the world and to implement the recommendations agreed in the 1996 London Workshop.10Rusch V.W. Asamura H. Watanabe H. et al.The IASLC lung cancer staging project. A proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification of lung cancer.J Thorac Oncol. 2009; 4: 568-577Abstract Full Text Full Text PDF PubMed Scopus (809) Google Scholar The IASLC lymph node map depicts nodal stations with clearly identifiable anatomical landmarks that are grouped in nodal zones. Although not perfect, it was the result of an international and multidisciplinary agreement to provide homogeneous guidance to classify nodal disease. A specific nodal chart for epithelial thymic tumors was also proposed by the International Thymic Malignancies Interest Group and the IASLC.11Bhora F.Y. Chen D.J. Detterbeck F.C. et al.The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: a proposed lymph node map for thymic epithelial tumors in the forthcoming 8th edition of the TNM classification of malignant tumors.J Thorac Oncol. 2014; 9: S88-S96Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar The SPFC Nodal Chart Subcommittee for lung cancer is working toward the improvement of the chart, especially on clarifying the borders separating N1 and N2 involvement. It also is refining the anatomical landmarks of certain nodal stations that are defined by a straight line in the map, but are curved in reality, as is the case of the superior rim of the left pulmonary artery. The addition of improved drawings, intraoperative pictures, and videos is planned to enhance homogeneity when classifying nodal disease. The review of previous definitions of complete resection, the consideration of the minimal requirements for a clinically acceptable intraoperative nodal evaluation, and the prognostic impact of positive pleural lavage cytology test led to several discussions in every meeting of the Staging Committee. In 2004, finally, the definitions of complete, uncertain, and incomplete resections were agreed on and subsequently published.12Rami-Porta R. Wittekind C. Goldstraw P. International Association for the Study of Lung Cancer (IASLC) Staging CommitteeComplete resection in lung cancer surgery: proposed definitions.Lung Cancer. 2005; 49: 25-33Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar One important feature in the definition of complete resection is the introduction of a standard intraoperative nodal evaluation that was what in 1996 defined as systematic nodal dissection (SND). SND has two steps. Step 1: the excision of all mediastinal fat and enclosed lymph nodes or, if this is not possible, at least the excision of three mediastinal nodal stations, always including the subcarinal. Step 2: the excision of the hilar and intrapulmonary lymph nodes in a centrifugal manner.1Goldstraw P. Report on the International workshop on intrathoracic staging. London, October 1996.Lung Cancer. 1997; 18: 107-111Abstract Full Text Full Text PDF Google Scholar When the definition of complete resection was discussed, there was new information on the preferential route of lymphatic spread depending on the lobar location of the primary tumor, and the alternative definition of step 1 of SND was refined by assigning three specific mediastinal nodal stations to be excised depending on the location of the tumor, the so-called lobe-specific SND.12Rami-Porta R. Wittekind C. Goldstraw P. International Association for the Study of Lung Cancer (IASLC) Staging CommitteeComplete resection in lung cancer surgery: proposed definitions.Lung Cancer. 2005; 49: 25-33Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar Six lymph nodes (three mediastinal and three hilar and intrapulmonary) were required as the minimum nodal dissection according to a contemporary report that established the optimal cut-point that significantly modified survival.13Gajra A. Newman N. Gamble G.P. Kohman L.J. Graziano S.L. Effect of the number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer.J Clin Oncol. 2003; 21: 1029-1034Crossref PubMed Scopus (254) Google Scholar SND weighs a lot in the definition of complete resection, so that when its minimum requirements are not met, and there is no evidence of residual disease, the resection is defined as uncertain, to separate it from incomplete resection which means that residual disease was left behind. Three independent groups with three different databases have validated these definitions, revealing they significantly separate three prognostic groups both in patients with tumors with and without nodal disease.14Rami-Porta R. Wittekind C. Goldstraw P. Complete resection in lung cancer surgery: from definition to validation and beyond.J Thorac Oncol. 2020; 15: 1815-1818Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The uncertain resection, coded as R0(un), was incorporated as a new category of the residual tumor descriptor in the seventh edition of TNM classification of malignant tumors. Defined as a resection associated with a suboptimal number of resected lymph nodes for all tumors, it also includes the involvement of the highest mediastinal node removed or sampled as a site-specific descriptor for lung cancer.15Explanatory notes—general.in: Wittekind C. Compton C.C. Brierley J. Sobin L.H. UICC TNM Supplement. A Commentary on Uniform Use. 4th ed. Wiley-Blackwell, Oxford, United Kingdom2012: 17Google Scholar All the objectives of the 1996 London Workshop have been fulfilled, and the IASLC Staging Project is still active with many new objectives ahead. As a result of these achievements, the IASLC is at the frontline of a worldwide staging effort to improve the classification of thoracic malignancies for which it is highly respected. As a result of the robust evidence-based revisions, the IASLC is now positioned as the most important provider of evidences to the UICC and the AJCC for the periodic revisions of the TNM classification of lung cancer, malignant pleural mesothelioma, and epithelial thymic tumors, and continues its agreement with the International Esophageal Study Group, replacing the WECC, for the production and dissemination of educational materials of the TNM classification of esophageal and esophagogastric juncture cancers. The 1996 London Workshop was an outstanding initiative from which the IASLC and the international thoracic oncology community of patients and doctors have benefited in a way that was difficult to anticipate 25 years ago.