The stage of disease describes the anatomic extent of the cancer.
The TNM subsets represent description of the primary tumor, the T factor, the status of the regional lymph nodes, the N factor, and the absence or presence of distant metastasis, the M factor.
Stage grouping is the combination of TNM subsets into seven stages of disease that reflect a hierarchy of survival expectations from the best outcome for stage I to the worst in Stage IV: Stage IA, IB, IIA, IIB, IIIA, IIIB, and IV.
All clinical observations and tests performed before the initiation of treatment are the basis for the clinical or cStage .
The postsurgical treatment-pathologic stage , pStage, is assigned on the basis of pathological examination of resected specimens.
A retreatment stage, rStage , may be assigned following initial or subsequent steps in a multistep treatment program, or at any point in the life history of the cancer.
Note: This chapter is divided into two sections: Section 1 deals with the current staging system in use, and Section 2 presents the proposed revisions to be incorporated in the seventh edition of the International System for Staging Lung Cancer as published by the International Association for the Study of Lung Cancer (IASLC).
CURRENT STAGING SYSTEM
The concept of staging derives from the significant relationship between the anatomic extent of the disease and prognosis in patients with lung cancer.
The International System for Staging Lung Cancer provides reproducible classification of the anatomic extent of the disease.
Limitations in treatment strategy are related to:
cStage of disease at diagnosis
Histologic cell type of the tumor
Patient performance status
INTERNATIONAL SYSTEM FOR STAGING LUNG CANCER
For the past 20 years, the scientific community has been well served by wide application of the International System for Staging Lung Cancer, shown in Tables 21-1 and 21-2 . These recommendations were derived and confirmed by analysis of a collected database of the survival experiences of more than 5000 patients with primary lung cancer treated in a contemporary time frame. The present classification was adopted in 1986, and with revisions, has been in place since that time; it has been included in the past and present published staging manuals of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). To reduce the inconsistency resulting from the use of multiple systems for classifying regional lymph nodes, recommendations for a lymph node mapping schema were adopted by the AJCC and the UICC that incorporate features of the most frequently used systems.
|Primary Tumor (T)|
|TX||Primary tumor cannot be assessed or tumor proven by the 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 or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus * (i.e., not in the main bronchus)|
|T2||Tumor with any of the following features of size or extent:|
|More than 3 cm in greatest dimension|
|Involves main bronchus, 2 cm or more distal to the carina|
|Invades the visceral pleura|
|Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.|
|T3||Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, or the mediastinal pleura or pericardium; or tumor in the main bronchus less than 2 cm distal to the carina, but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung.|
|T4||Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural or pericardial effusion † , or with satellite tumor nodule(s) within the ipsilateral primary-tumor lobe of the lung.|
|Regional Lymph Nodes (N)|
|NX||Regional lymph nodes cannot be assessed|
|N0||No regional lymph node metastasis|
|N1||Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes involved by direct extension of the primary tumor|
|N2||Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s)|
|N3||Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)|
|Distant Metastasis (M)|
|MX||Presence of distant metastasis cannot be assessed|
|M0||No distant metastasis|
|M1||Distant metastasis present ‡ Specify site(s)|
† T4 : Most pleural effusions associated with lung cancer are due to tumor. There are, however, some few patients in whom cytopathologic examination of pleural fluid (on more than one specimen) is negative for tumor, the fluid is nonbloody and is not an exudate. In such cases where these elements and clinical judgment dictate that the effusion is not related to the tumor, the patients should be staged T1, T2, or T3, excluding effusion as a staging element.
|Stage 0||Carcinoma in situ|
|Stage IA||T1 N0 M0|
|Stage IB||T2 N0 M0|
|Stage IIA||T1 N1 M0|
|Stage IIB||T2 N1 M0|
|T3 N0 M0|
|Stage IIIA||T3 N1 M0|
|T1 N2 M0|
|T2 N2 M0|
|T3 N2 M0|
|Stage IIIB||T4 N0 M0 T4 N1 M0|
|T4 N2 M0|
|T1 N3 M0 T2 N3 M0|
|T3 N3 M0 T4 N3 M0|
|Stage IV||Any T Any N M1|
End results studies according to staging factors provide a benchmark for:
Entering patients into clinical trials
Comparing the effectiveness of differing treatments
Evaluating new prognostic factors
Histologic Cell Type
The staging system is applicable for the four major cell types of lung cancer, described in the 2004 World Health Organization Classification of Lung Tumors. This classification emphasizes morphologic aspects of diagnosis using light microscopy and provides a standard nomenclature and criteria for diagnosis that can be used by pathologists worldwide.
Squamous cell carcinoma
Adenocarcinoma (including bronchioalveolar carcinoma)
Large cell carcinoma
Small cell carcinoma
Specific TNM staging is useful for small cell lung cancer (SCLC), particularly for selecting patients for multimodality programs involving adjuvant surgery. The proportion of patients achieving a complete response to treatment, the duration of the response, and recurrence after a complete response is directly related to the extent of the disease at diagnosis.
Other Factors and the Present System
Many factors are reported to have significant influence on the outcome in patients with lung cancer.
Literature describing prognosis according to the presence or absence of molecular genetic markers, growth factors and receptors, and pathologic factors, such as angiogenesis and cell proliferation, is now available.
In this milieu of evolving knowledge of the molecular biology of lung cancer, its initiation, growth and metastasis, the stage of disease is a standard for evaluating the effect on survival of new factors derived from the research.
Staging and histologic classifications remain relevant as major indicators of the curative potential and limitations of available therapy for lung cancer.
TNM Numeric Descriptors
T—Primary tumor (see Table 21-1 )
Four distinct levels of tumor progression are classified according to tumor size, location, and extent of invasion, TX, T0, T1, T2, T3, T4.
Implications for staging uncommon, limited, superficial tumors and for pleural effusion are addressed in footnotes to Table 21-1 .
N—Regional lymph nodes
Classification is based on anatomic considerations, that is, the relationship of the nodal drainage to the primary tumor, N0, N1, N2, N3.
Identifies the absence or presence of metastasis to distant organ sites and distant lymph nodes, M0, M1. The implications for staging of separate metastatic nodules in the ipsilateral nonprimary tumor lobe or lobes are addressed in footnotes to Table 21-1 .
Staging in the Life History of the Disease
Identical staging descriptors are useful and applicable at specific points in the life history of the lung cancer.
All patients are assigned a clinical stage, which is not changed throughout the course of the disease.
Importance of clinical staging cannot be overestimated; it is precisely this information that influences treatment selection in most patients.
Sequencing of diagnostic tests usually proceeds from the chest roentgenograms (CXRs) and computed tomographic scans (CTs) and tests to rule out distant metastasis, to examinations for confirming the extent of the primary tumor and the status of regional lymph nodes. The clinical stage includes the results of
Imaging: CXR; CT; positron emission tomography; magnetic resonance imaging; bone scanning
Fine-needle aspiration biopsy
Transesophageal ultrasound with fine-needle aspiration biopsy may be included; however, it is limited to examination of the posterior mediastinum.
For patients assigned to surgical treatment, pathologic examination of resected specimens provides more accurate description of the extent of the primary tumor and regional lymph node metastasis than may be obtained from clinical observations and tests. Except for identifying possible intrapulmonary metastasis, pStage provides no additional information about the cM category.
Evaluation of the extent of disease in multimodality therapy programs is useful for assigning subsequent treatment and measuring results of each therapeutic step.
It is useful to specify the evaluations used and the type of staging in end results reports. For example, cStage that includes the results of mediastinoscopy/mediastinotomy provides more accurate evaluation of regional nodes than cStage that does not include the procedure.
STAGE GROUPING AND SURVIVAL PATTERNS
The TNM subsets, combined in seven stage groups, in addition to a stage 0, are shown in Table 21-2 ; Figures 21-1 through 21-6 are diagrammatic illustrations of each stage. The implications of the stage classifications for survival rates, according to clinical and surgical pathologic criteria for NSCLC are shown in Figures 21-7 and 21-8 , and for SCLC in Figure 21-9 . Erosion of prognosis as the lung cancer progresses from stage IA through stage IV reflects the efficacy of treatment, prognosis, and the usefulness of the classification system.
Stage 0 is assigned to patients with carcinoma in situ.
Stage IA is reserved for patients with small tumors, less than or equal to 3 cm in greatest dimension, and with no evidence of any metastasis (see Fig. 21-1 ). The prognosis for these patients is significantly better than that for patients in any other stage, according to both clinical and surgical-pathologic criteria. Figures 21-7 and 21-8 show cumulative 5-year survival rates of 61% for cStage IA patients and 67% for the pStage IA patients with non–small cell lung cancer (NSCLC).
Stage IB classifies increasing tumor size and invasiveness, and the presence of associated atelectasis or obstructive pneumonitis; no metastasis is evident, and the proximal extent of disease is at least 2 cm distal to the main carina (see Fig. 21-2 ). A significant difference between the survival rates for patients with stage IA and those with stage IB NSCLC is documented in Figures 21-7 and 21-8 , according to both clinical and surgical pathologic criteria.
Stage IIA identifies one subset of patients with small primary tumors and limited metastasis to intrapulmonary, including hilar, lymph nodes. These tumors infrequently are diagnosed clinically; however, in patients undergoing surgical treatment, stage migration to this category is common (see Fig. 21-3 ) (n = 26, cT1 N1 M0; n = 76, sT1 N1 M0). The survival rates for patients with NSCLC, according to clinical and surgical-pathologic criteria, does not differ significantly from the stage IB groups (see Figs. 21-7 and 21-8 ); however, a specific classification is needed to accumulate data for further study. Radiographic examples of Stage IIA are shown in Figure 21-10A to C .
Stage IIB includes two anatomic subsets of patients, classified T2 N1 M0 and T3 N0 M0 (see Fig. 21-4 ). The relationship to survival rates is similar for patients with NSCLC in both of these subgroups: cT2 N1 M0 and cT3 N0 M0, 26% and 21%, respectively, expected to survive 5 years after treatment; pT2 N1 M0 and pT3 N0 M0, 39% and 38% respectively, expected to survive 5 years after treatment. A significant difference in survival rates is shown in Figure 21-7 for patients with cStage IIA NSCLC compared with those with cStage IIB, in which 37% and 24% of patients, respectively, are expected to survive 5 years or more after treatment. In the surgical treatment subset of patients, a significant difference in outcome between pStage IIA and pStage IIB patients also is observed, 55% and 39% respectively expected to survive 5 years after treatment (see Fig. 21-8 ). Radiographic examples of Stage IIB are shown in Figure 21-11A to B .
Stage IIIA reflects the implications of ipsilateral, limited extrapulmonary extension of the lung cancer. Classification is provided for four anatomic subsets of patients with extrapulmonary disease and no distant metastasis: Extrapulmonary extension of the primary tumor and metastasis to intrapulmonary, including hilar lymph nodes, is classified as T3 N1 M0, and, T1 N2 M0, T2 N2 M0, and T3 N2 M0 tumors with evidence of metastasis to the ipsilateral mediastinal and subcarinal lymph nodes (see Fig. 21-5 ). The serious effect on prognosis of clinically detectable lymph node metastasis is shown in the cumulative survival rates for patients with NSCLC in the cT3 N1 M0 and cT1-2-3 N2 M0 subsets, 9% and 13%, respectively, expected to survive 5 years after treatment. Figure 21-7 shows the survival pattern for the cStage IIIA group overall. Selected patients with pStage IIIA NSCLC tumors in whom a complete resection of all known disease is anticipated may have a better prognosis than Stage IIIA patients who are not surgical candidates. Similar cumulative survival rates were observed for patients with NSCLC undergoing surgical treatment in the pT3 N1 M0 and pT1-2-3 N2 M0 groups; 25% and 23% of patients, respectively, expected to survive 5 years after treatment. The survival pattern overall for the pStage IIIA patients is shown in Figure 21-8 . Radiographic examples of Stage IIIA are shown in Figure 21-12A to B .