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J Thorac Oncol. 2016 May;11(5):651-665. doi: 10.1016/j.jtho.2016.01.025. Epub 2016 Mar 2.

The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer.

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Department of Surgery, Yale University, New Haven, Connecticut. Electronic address:
Department of Pathology, University of Colorado, Denver, Colorado.
Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College, London, United Kingdom.
Respiratory Medicine Service, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Department of Pathology, Sloan-Kettering Cancer Center, New York, New York.
Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio.
Department of Diagnostic Imaging, Tel-Aviv University, Ramat Gan, Israel.
Department of Thoracic Surgery, New York University, New York, New York.
Department of Internal Medicine, Yale University, New Haven, Connecticut.
Thoracic Surgery Service, Sloan-Kettering Cancer Center, New York, New York.
Division of Thoracic Surgery, Keio University, School of Medicine, Tokyo, Japan.
Thoracic Surgery Service, Hospital Universitari Mutua Terrassa, Barcelona, Spain; Centros de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) Lung Cancer Group, Terrassa, Barcelona, Spain.



It can be difficult to distinguish between a second primary and a metastasis in patients with lung cancer who have more than one pulmonary site of cancer.


A systematic review of the literature was conducted by a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee to develop recommendations to identify second primary lung cancers. The process entailed review of knowledge relating to the mechanism of metastasis, determination of clonality, and outcomes of patients with resected tumors.


It is easier to determine that two tumors are different than that they are the same; finding similarities does not establish that they are the same. For example, most second primary lung cancers are of the same histotype. Few criteria are reliable by themselves; these include different histologic cancer types or matching DNA breakpoints by sequencing and a comprehensive histologic assessment of resected specimens. Characteristics that are suggestive but associated with potential misclassification include the presence or absence of biomarkers, imaging characteristics, and the presence or absence of nodal involvement.


Clinical and pathologic (i.e., after resection) criteria are presented to identify two foci as separate primary lung cancers versus a metastasis. Few features are definitive; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification. Careful review by a multidisciplinary tumor board, considering all available information, is recommended.


Lung cancer; Lung cancer staging; Multiple tumors; Non–small cell lung cancer; TNM classification

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