INTRODUCTION — The tumor, node, metastasis (TNM) staging system for lung cancer is an internationally accepted system used to characterize the extent of disease. The TNM system combines features of the tumor into disease stage groups that correlate with survival and are linked to recommendations for treatment. Despite frequent updates to the staging system, the links between stage and treatment are becoming substantially more complex. Older studies of stage-specific treatments were performed at a time that predated the staging techniques and treatments of modern clinical practice, which now include enhanced imaging, more accurate biopsy techniques, as well as biochemical and molecular characterization.
This topic discusses the TNM staging system for lung cancer. The purpose of TNM staging is to provide a description of the anatomic extent of cancer that can be easily communicated to others, assist in treatment decisions, and serve as an indicator of prognosis. Consistent application of staging criteria permits valid comparisons of patient cohorts, particularly in regards to the outcomes associated with different therapeutic options. In clinical practice, TNM stage is combined with the unique clinical characteristics of the patient and, in some cases, the molecular features of the tumor itself to guide prognostic assessment and treatment selections.
The eighth edition of the TNM staging system and the evidence supporting it are described in this topic (table 1 and table 2 and table 3) [1,2]. The eighth edition is effective as of January 1, 2018, both in the United States and elsewhere. The clinical manifestations, diagnosis, pathology, and management of lung cancer are discussed in other topics.
●(See "Clinical manifestations of lung cancer".)
●(See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer".)
●(See "Overview of the initial treatment and prognosis of lung cancer".)
●(See "Management of stage I and stage II non-small cell lung cancer".)
●(See "Systemic therapy in resectable non-small cell lung cancer".)
●(See "Management of stage III non-small cell lung cancer".)
●(See "Overview of the initial treatment of advanced non-small cell lung cancer".)
●(See "Pathology of lung malignancies".)
PATHOLOGIC, CLINICAL AND OTHER STAGING DISTINCTIONS — Different staging systems are used prior to and after surgical resection, as described below.
●Clinical-diagnostic staging – Clinical-diagnostic staging (cTNM) is based primarily on imaging findings with or without additional information from minimally invasive biopsy procedures, such as endobronchial ultrasound-guided biopsy.
●Surgical-pathologic staging – TNM staging is described as surgical pathologic (pTNM) when it is based on findings combined from surgical resection or exploration of the primary tumor and lymph nodes with additional information from clinical imaging studies.
The individual definitions of the T, N and M categories are the same whether assessed clinically or pathologically (table 1). The same TNM groupings are used to determine the clinical-diagnostic stage and surgical-pathologic stage, as well as retreatment stage and autopsy stage (table 3). The suffix "X" is attached (ie, TX, NX) if the extent of disease cannot be assessed for any of these features.
RATIONALE FOR DISTINCTION BETWEEN NSCLC AND SCLC — Lung cancer has been subclassified into these two major categories (non-small cell lung cancer [NSCLC] and small cell lung carcinoma [SCLC]) as the result of differences in clinical features, approach to treatment, and clinical outcomes. In general, SCLC tends to have a faster growth rate, more central localization, earlier metastasis to mediastinal and extrathoracic sites, and shorter overall survival time.
SCLC is usually staged and managed using a simplified system of clinical-limited or clinical-extensive disease. The main role for TNM staging in SCLC is to improve the specificity of information contained in clinical cancer registries and clinical research. Analyses performed for the eighth edition of the TNM system confirm that the TNM system is applicable to SCLC and allows prognostication, with worse survival for more advanced stages [2]. (See "Pathobiology and staging of small cell carcinoma of the lung", section on 'Staging'.)
EIGHTH EDITION OF THE TNM SYSTEM — The eighth edition was a planned revision of the previous edition to incorporate new survival data gained from advances in imaging techniques, clinical testing, and therapeutics [2].
To inform the eighth edition of the TNM staging system, the International Association for the Study of Lung Cancer developed a database of approximately 95,000 patients with lung cancer who were treated in 16 countries between 1999 and 2010 (table 1 and table 3) [1,3,4]. For reference purposes, comparison with seventh edition staging is shown in the table (table 2 and table 4). The eighth edition of the staging system was derived from analysis of a diverse population of approximately 95,000 patients. Data from 70,967 patients with non-small cell lung cancer were used to retrospectively validate the prognostic value of the TNM descriptors [3].
As with previous editions, the current edition of the TNM staging system categorizes tumors on the basis of primary tumor characteristics (T), the presence or absence of regional lymph node involvement (N), and the presence or absence of distant metastases (M). Molecular tumor features of lung cancer are not included in the TNM system. The overall stage of the tumor (stage I through IV) is determined by the combination of T, N, and M descriptors (table 3).
Prognosis by stage — Under the eighth edition of the TNM staging system, the median survival correlates with both the clinical stage and surgical-pathologic stage. The survival according to clinical and pathologic staging for the eighth edition (and seventh edition, for comparison) is shown in the figures (figure 1 and figure 2).
Primary tumor (T) classification — The primary distinction between T classification categories is tumor size. Other features, including invasion of proximal airways, mediastinal involvement, pleural involvement, and extension through the diaphragm or chest wall, also define distinct prognostic categories and correlate with surgical resectability. Combined, these features may be grouped into distinct prognostic categories (figure 3).
●Tx - Primary tumor cannot be assessed or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy.
●T0 – No evidence of primary tumor.
●Tis – Carcinoma in situ.
●T1 – Tumor ≤3 cm in greatest dimension surrounded by lung or visceral pleura without bronchoscopic evidence of invasion more proximal than the lobar bronchus (ie, not in the main bronchus).
•T1a(mi) – Minimally invasive adenocarcinoma (solitary adenocarcinoma, ≤3 cm with a predominately lepidic pattern and ≤5 mm invasion in any one focus)
•T1a – Tumor ≤1 cm in greatest dimension
•T1b – Tumor >1 but ≤2 cm in greatest dimension
•T1c – Tumor >2 but ≤3 cm in greatest dimension
●T2 - Tumor >3 but ≤5 cm or tumor with any of the following features:
•Involves main bronchus regardless of distance from the carina but without involvement of the carina
•Invades visceral pleura
•Associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung
-T2a – Tumor >3 but ≤4 cm in greatest dimension
-T2b – Tumor >4 but ≤5 cm in greatest dimension
●T3 - Tumor >5 but ≤7 cm in greatest dimension or associated with separate tumor nodule(s) in the same lobe as the primary tumor or directly invades any of the following structures: chest wall (including the parietal pleura and superior sulcus tumors), phrenic nerve, and parietal pericardium.
●T4 - Tumor >7 cm in greatest dimension or associated with separate tumor nodule(s) in a different ipsilateral lobe than that of the primary tumor or invades any of the following structures: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, and carina.
Regional lymph node (N) classification — The lymph node classification is determined by the location of the lymph node in relationship to the primary tumor and hilum, mediastinum, and contralateral hilar regions. As with the tumor designations, this classification correlates with survival (figure 4).
●Nx – Regional lymph nodes cannot be assessed.
●N0 – No regional lymph node metastasis.
●N1 – Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph node(s) and intrapulmonary nodes, inducing involvement by direct extension.
●N2 – Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
●N3 – Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
Although these N descriptors from the prior edition consistently predicted prognosis and were carried forward unchanged in the eighth edition, an exploratory subclassification of pathologic (surgically staged) N1 and N2 disease based on the number of involved nodal stations and individual nodes has been proposed (figure 4) [2,5]:
●pN1 – Involvement of ipsilateral intrapulmonary, peribronchial, or hilar lymph nodes.
•pN1a – Single-station metastasis.
•pN1b – Multiple-station metastasis.
●pN2 – Involvement of ipsilateral mediastinal or subcarinal lymph nodes.
•pN2a1 – Single N2 station without concurrent N1 station involvement (skip metastasis).
•pN2a2 – Single N2 station with concurrent N1 involvement.
•pN2b – Multiple N2 station metastasis.
Distant metastasis (M) classification — The primary determinants of prognosis in patients with metastatic disease are determined by the presence of metastasis within the thorax, extrathoracic metastasis, and the presence of malignant pericardial or pleural effusions (figure 5).
●M0 – No distant metastasis.
●M1 – Distant metastasis present.
•M1a – Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodule(s) or malignant pleural or pericardial effusion.
•M1b – Single extrathoracic metastasis.
•M1c – Multiple extrathoracic metastasis in one or more organs.
Stage groupings — Stage groupings reflect prognosis groupings whether clinically or pathologically staged. The eighth edition staging system has refined the stage groupings by increasing the number of stage subcategories (figure 1 and figure 2 and table 3).
Summary of differences between eighth and seventh editions — Revisions to the seventh edition were made in order to improve the prognostic ability of the staging categories and cutoff points. The eighth edition is effective as of January 1, 2018, both in the United States and elsewhere, replacing previous systems (table 1 and table 2) [2]. The seventh edition is shown for reference in the table (table 4) [6].
Primary tumor — Major changes between the seventh and the eighth editions include the following [1,2]:
●T1 changes – New stage groupings divide T1 tumors into T1a (≤1 cm), T1b (>1 to ≤2 cm), and T1c (>2 to ≤3 cm).
●T2 changes – T2 tumors have a size cutoff of 5 cm now, rather than 7 cm. Involvement of the mainstem bronchus, regardless of distance from carina, is now T2 rather than T3. Both partial and total atelectasis/pneumonitis are now T2.
●T3 and T4 changes – Tumors > 5 to ≤7 cm are now T3 instead of T2; tumors > 7 cm now fall into a new T4A grouping. Diaphragm invasion is now T4 rather than T3.
Metastasis — The eighth edition of the TNM staging created a new category, M1b, designating a single extrathoracic metastasis, which is distinguished from M1c, in which there are multiple metastatic lesions (in one or multiple organs (table 1)). These changes led to the designation of stage IVA disease, in which disease is limited to either intrathoracic metastatic involvement or a single extrathoracic metastasis, versus stage IVB disease, in which multiple extrathoracic metastases exist. It is intended that this degree of precision will ultimately help guide treatment options for oligometastatic disease. (See "Oligometastatic non-small cell lung cancer" and "Limited-stage small cell lung cancer: Initial management".)
Changes to the stage groupings — Changes made in the eighth edition TNM categories have resulted in alterations in assigned disease stage primarily by increasing the number of stage subcategories (table 2) [2].
As an example, a new disease category stage IIIC has been created for patients with N3 disease and either a T3 or T4 primary lesion [1]. This new category reflects the poor prognosis of such cancers relative to stage IIIB cancers. Although the prognosis for stage IIIC disease is similar to stage IV disease, the distinction is made due to different treatment approaches available for locally advanced, nonmetastatic disease. (See "Management of stage III non-small cell lung cancer", section on 'Clinical mediastinal (N2, N3) involvement' and "Overview of the initial treatment of advanced non-small cell lung cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Introduction
•The tumor, node, metastasis (TNM) staging system for lung cancer is an internationally accepted system used to characterize the extent of disease. The purpose of TNM staging is to provide a description of the extent of cancer that can be easily communicated to others, assist in treatment decisions, and serve as a prognostic indicator. (See 'Introduction' above.)
•The TNM staging system relies on anatomic, macroscopic groupings of disease with similar prognoses rather than on molecular characterization. (See 'Introduction' above.)
●Eighth edition of the TNM system
•The TNM staging system predicts survival, but should not be used alone to dictate treatment. Periodic revisions are necessary because advanced imaging techniques and treatments continue to evolve and impact survival. (See 'Eighth edition of the TNM system' above.)
•The most recent version of the TNM staging system is the eighth edition of the "TNM Classification of Malignant Tumors," effective as of January 1, 2018, both in the United States and elsewhere. The eighth edition includes new tumor stage groupings and refinements of the T and M descriptors (table 1 and table 3). The seventh edition is shown for comparison (table 4). (See 'Summary of differences between eighth and seventh editions' above.)
-The eighth edition continues the trend initiated in previous additions to emphasize size cutoffs, such that there are distinct categories for each cm increase in size from 1 to 5 cm. (See 'Primary tumor' above.)
-Although there were no changes in the N descriptors from the seventh to the eighth editions, the eighth edition makes the additional recommendation to quantify nodal disease by the number of involved nodal stations. (See 'Regional lymph node (N) classification' above.)
-Metastatic disease is divided according to whether metastatic disease is limited to the chest, and if not, whether there are single or multiple extrathoracic sites of metastasis. (See 'Metastasis' above.)
