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Non-Small Cell Lung Cancer Treatment (PDQ®)

Stage Information for NSCLC

Background

In NSCLC, the determination of stage is important in terms of therapeutic and prognostic implications. Careful initial diagnostic evaluation to define the location and to determine the extent of primary and metastatic tumor involvement is critical for the appropriate care of patients.

In general, symptoms, physical signs, laboratory findings, or perceived risk of distant metastasis lead to an evaluation for distant metastatic disease. Additional tests such as bone scans and computed tomography (CT)/magnetic resonance imaging (MRI) of the brain may be performed if initial assessments suggest metastases or if patients with stage III disease are under consideration for aggressive local and combined modality treatments.

Stage has a critical role in the selection of therapy. The stage of disease is based on a combination of clinical factors and pathological factors.[1] The distinction between clinical stage and pathological stage should be considered when evaluating reports of survival outcome.

Procedures used to determine staging include the following:

  • History.
  • Physical examination.
  • Routine laboratory evaluations.
  • Chest x-ray.
  • Chest CT scan with infusion of contrast material.
  • Fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning.

Procedures used to obtain tissue samples include bronchoscopy, mediastinoscopy, or anterior mediastinotomy. Pathological staging of NSCLC requires the following:

  • Examination of the tumor.
  • Resection margins.
  • Lymph nodes.

Prognostic and treatment decisions are based on some of the following factors:

  • Knowledge of histologic type.
  • Tumor size and location.
  • Involvement of pleura.
  • Surgical margins.
  • Status and location of lymph nodes by station.
  • Tumor grade.
  • Lymphovascular invasion.

At diagnosis, patients with NSCLC can be divided into the following three groups that reflect both the extent of the disease and the treatment approach:

  1. Surgically resectable disease (generally stage I, stage II, and selected stage III tumors).
    • Has the best prognosis, which depends on a variety of tumor and host factors.
    • Patients with resectable disease who have medical contraindications to surgery are candidates for curative radiation therapy.
    • Postoperative cisplatin-based combination chemotherapy may provide a survival advantage to patients with resected stage II or stage IIIA NSCLC.
  2. Locally (T3–T4) and/or regionally (N2–N3) advanced disease.
    • Has a diverse natural history.
    • Selected patients with locally advanced tumors may benefit from combined modality treatments.
    • Patients with unresectable or N2-N3 disease are treated with radiation therapy in combination with chemotherapy.
    • Selected patients with T3 or N2 disease can be treated effectively with surgical resection and either preoperative or postoperative chemotherapy or chemoradiation therapy.
  3. Distant metastatic disease (includes distant metastases [M1] that were found at the time of diagnosis).
    • May be treated with radiation therapy or chemotherapy for palliation of symptoms from the primary tumor.
    • Patients with good performance status, women, and patients with distant metastases confined to a single site live longer than others.[2]
    • Platinum-based chemotherapy has been associated with short-term palliation of symptoms and with a survival advantage.
    • Currently, no single chemotherapy regimen can be recommended for routine use.
    • Patients previously treated with platinum combination chemotherapy may derive symptom control and survival benefit from docetaxel, pemetrexed, or epidermal growth factor receptor inhibitors.

Staging Evaluation

Evaluation of mediastinal lymph node metastasis

Surgical evaluation

Surgical staging of the mediastinum is considered standard if accurate evaluation of the nodal status is needed to determine therapy.

Accurate staging of the mediastinal lymph nodes provides important prognostic information.

Evidence (nodal status):

  1. The association between survival and the number of examined lymph nodes during surgery for patients with stage I NSCLC treated with definitive surgical resection was assessed from the population-based Surveillance, Epidemiology and End Results database for the period from 1990 to 2000.[3] A total of 16,800 patients were included in the study.
    • The overall survival (OS) analysis for patients without radiation therapy demonstrated that in comparison to the reference group (one to four lymph nodes), patients with five to eight lymph nodes examined during surgery had a modest but statistically significant increase in survival, with a proportionate hazard ratio (HR) of 0.90 (95% confidence interval [CI], 0.84–0.97). For patients with 9 to 12 lymph nodes and 13 to 16 lymph nodes examined, HRs were 0.86 (95% CI, 0.79–0.95) and 0.78 (95% CI, 0.68–0.90), respectively. There appeared to be no incremental improvement after evaluating more than 16 lymph nodes. The corresponding results for lung cancer–specific mortality and for patients receiving radiation therapy were not substantially different.
    • These results indicate that patient survival following resection for NSCLC is associated with the number of lymph nodes evaluated during surgery. Because this is most likely the result of a reduction-of-staging error, namely, a decreased likelihood of missing positive lymph nodes with an increasing number of lymph nodes sampled, it suggests that an evaluation of nodal status should include 11 to 16 lymph nodes.
CT imaging

CT scanning is primarily used for determining the size of the tumor. The CT scan should extend inferiorly to include the liver and adrenal glands. MRI scans of the thorax and upper abdomen do not appear to yield advantages over CT scans.[4]

Evidence (CT scan):

  1. A systematic review of the medical literature relating to the accuracy of CT scanning for noninvasive staging of the mediastinum in patients with lung cancer has been conducted. In the 35 studies published between 1991 and June 2006, 5,111 evaluable patients were identified. Almost all studies specified that CT scanning was performed following the administration of IV contrast material and that a positive test result was defined as the presence of one or more lymph nodes that measured larger than 1 cm on the short-axis diameter.[5]
    • The median prevalence of mediastinal metastasis was 28% (range, 18%–56%).
    • The pooled sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were 51% (95% CI, 47%–54%) and 86% (95% CI, 84%–88%), respectively. The corresponding positive and negative likelihood ratios were 3.4 and 0.6, respectively.
  2. The results from the systematic review are similar to those of a large meta-analysis that reported the median sensitivity and specificity of CT scanning for identifying malignant mediastinal nodes as 61% and 79%, respectively.[6]
  3. An earlier meta-analysis reported average sensitivity and specificity of 64% and 74%, respectively.[7]
FDG-PET scanning

The wider availability and use of FDG-PET scanning for staging has modified the approach to staging mediastinal lymph nodes and distant metastases.

Randomized trials evaluating the utility of FDG-PET scanning in potentially resectable NSCLC report conflicting results in terms of the relative reduction in the number of noncurative thoracotomies.

Although the current evidence is conflicting, FDG-PET scanning may improve results of early-stage lung cancer by identifying patients who have evidence of metastatic disease that is beyond the scope of surgical resection and that is not evident by standard preoperative staging procedures.

Evidence (FDG-PET scan):

  1. A systematic review, an expansion of a health technology assessment conducted in 2001 by the Institute for Clinical and Evaluative Sciences, evaluated the accuracy and utility of FDG-PET scanning in the diagnosis and staging of lung cancer.[8] Through a systematic search of the literature, 12 evidence summary reports and 15 prospective studies of the diagnostic accuracy of FDG-PET scanning were identified. FDG-PET scanning appears to be superior to CT imaging for mediastinal staging in NSCLC. FDG-PET scanning also appears to have high sensitivity and reasonable specificity for differentiating benign from malignant lesions as small as 1 cm.
  2. A systematic review of the medical literature relating to the accuracy of FDG-PET scanning for noninvasive staging of the mediastinum in patients with lung cancer identified 44 studies published between 1994 and 2006 with 2,865 evaluable patients.[5] The median prevalence of mediastinal metastases was 29% (range, 5%–64%). Pooled estimates of sensitivity and specificity for identifying mediastinal metastasis were 74% (95% CI, 69%–79%) and 85% (95% CI, 82%–88%), respectively. Corresponding positive and negative likelihood ratios for mediastinal staging with FDG-PET scanning were 4.9 and 0.3, respectively. These findings demonstrate that FDG-PET scanning is more accurate than CT scanning for staging of the mediastinum in patients with lung cancer.
Cost effectiveness of FDG-PET scanning

Decision analyses demonstrate that FDG-PET scanning may reduce the overall costs of medical care by identifying patients with falsely negative CT scans in the mediastinum or otherwise undetected sites of metastases.[9-11] Studies concluded that the money saved by forgoing mediastinoscopy in FDG-PET-positive mediastinal lesions was not justified because of the unacceptably high number of false-positive results.[9-11] A randomized study found that the addition of FDG-PET scanning to conventional staging was associated with significantly fewer thoracotomies.[12] A second randomized trial evaluating the impact of FDG-PET scanning on clinical management found that FDG-PET scanning provided additional information regarding appropriate stage but did not lead to significantly fewer thoracotomies.[13]

Combination of CT imaging and FDG-PET scanning

The combination of CT imaging and FDG-PET scanning has greater sensitivity and specificity than CT imaging alone.[14]

Evidence (CT/FDG-PET scan):

  1. If there is no evidence of distant metastatic disease on CT scan, FDG-PET scanning complements CT scan staging of the mediastinum. Numerous nonrandomized studies of FDG-PET scanning have evaluated mediastinal lymph nodes using surgery (i.e., mediastinoscopy and/or thoracotomy with mediastinal lymph node dissection) as the gold standard of comparison.
  2. In a meta-analysis evaluating the conditional test performance of FDG-PET scanning and CT scanning, the median sensitivity and specificity of FDG-PET scans were reported as 100% and 78%, respectively, in patients with enlarged lymph nodes.[6] FDG-PET scanning is considered very accurate in identifying malignant nodal involvement when nodes are enlarged. However, FDG-PET scanning will falsely identify a malignancy in approximately one-fourth of patients with nodes that are enlarged for other reasons, usually as a result of inflammation or infection.[15,16]
  3. The median sensitivity and specificity of FDG-PET scanning in patients with normal-sized mediastinal lymph nodes were 82% and 93%, respectively.[6] These data indicate that nearly 20% of patients with normal-sized nodes but with malignant involvement had falsely negative FDG-PET scan findings.

For patients with clinically operable NSCLC, the recommendation is for a biopsy of mediastinal lymph nodes that were found to be larger than 1 cm in shortest transverse axis on chest CT scan or were found to be positive on FDG-PET scan. Negative FDG-PET scanning does not preclude biopsy of radiographically enlarged mediastinal lymph nodes. Mediastinoscopy is necessary for the detection of cancer in mediastinal lymph nodes when the results of the CT scan and FDG-PET scan do not corroborate each other.

Evaluation of brain metastasis

Patients at risk for brain metastases may be staged with CT or MRI scans. One study randomly assigned 332 patients with potentially operable NSCLC and no neurological symptoms to brain CT or MRI imaging to detect occult brain metastasis before lung surgery. MRI showed a trend towards a higher preoperative detection rate than CT scan (P = .069), with an overall detection rate of approximately 7% from pretreatment to 12 months after surgery.[17] Patients with stage I or stage II disease had a detection rate of 4% (i.e., eight detections out of 200 patients); however, individuals with stage III disease had a detection rate of 11.4% (i.e., 15 detections out of 132 patients). The mean maximal diameter of the brain metastases was significantly smaller in the MRI group. Whether the improved detection rate of MRI translates into improved outcome remains unknown. Not all patients are able to tolerate MRI, and for these patients contrast-enhanced CT scan is a reasonable substitute.

Evaluation of distant metastasis other than the brain

Numerous nonrandomized, prospective, and retrospective studies have demonstrated that FDG-PET scanning seems to offer diagnostic advantages over conventional imaging in staging distant metastatic disease; however, standard FDG-PET scans have limitations. FDG-PET scans may not extend below the pelvis and may not detect bone metastases in the long bones of the lower extremities. Because the metabolic tracer used in FDG-PET scanning accumulates in the brain and urinary tract, FDG-PET scanning is not reliable for detection of metastases in these sites.[17]

The Revised International System for Staging Lung Cancer

The Revised International System for Staging Lung Cancer, based on information from a clinical database of more than 5,000 patients, was adopted in 2010 by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer.[18,19] These revisions provide greater prognostic specificity for patient groups; however, the correlation between stage and prognosis predates the widespread availability of PET imaging.

Summary of Changes

This staging system is now recommended for the classification of both NSCLC and small cell lung carcinomas and for carcinoid tumors of the lung.[19]

The T (primary tumor) classifications have been redefined as follows:[19]

  • T1 has been subclassified into T1a (≤2 cm in size) and T1b (>2–3 cm in size).
  • T2 has been subclassified into T2a (>3–5 cm in size) and T2b (>5–7 cm in size).
  • T2 (>7 cm in size) has been reclassified as T3.
  • Multiple tumor nodules in the same lobe have been reclassified from T4 to T3.
  • Multiple tumor nodules in the same lung but a different lobe have been reclassified from M1 to T4.

No changes have been made to the N (regional lymph nodes) classification. However, a new international lymph node map defining the anatomical boundaries for lymph node stations has been developed.

The M (distant metastasis) classifications have been redefined as follows:

  • M1 has been subdivided into M1a and M1b.
  • Malignant pleural and pericardial effusions have been reclassified from T4 to M1a.
  • Separate tumor nodules in the contralateral lung are considered M1a.
  • M1b designates distant metastasis.
Table 1. Stage Grouping Comparisons: Sixth Edition Versus Seventh Edition Descriptors, T and M Categories, and Stage Groupingsa,b
Sixth Edition T/M Descriptor (cm)Seventh Edition T/MN0N1N2N3
T = primary tumor; N0 = no regional lymph node metastasis; N1 = metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including 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); M = distant metastasis.
aCells in bold indicate a change from the sixth edition for a particular TNM category.
bReprinted with permission from Goldstraw 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 2:706-14, 2007.
T1 (≤2)T1aIAIIAIIIAIIIB
T1 (>2–3)T1bIAIIAIIIAIIIB
T2 (≤5)T2aIBIIA IIIAIIIB
T2 (>5–7)T2bIIA IIBIIIAIIIB
T2 (>7)T3IIB IIIA IIIAIIIB
T3 invasionT3IIBIIIAIIIAIIIB
T4 (same lobe nodules)T3IIB IIIA IIIA IIIB
T4 (extension)T4IIIA IIIA IIIBIIIB
M1 (ipsilateral lung)T4IIIA IIIA IIIB IIIB
T4 (pleural effusion)M1aIV IV IV IV
M1 (contralateral lung)M1aIVIVIVIV
M1 (distant)M1bIVIVIVIV

AJCC Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM classification to define NSCLC.[19]

Table 2. Definitions of TNM Occult Carcinomaa
StageTNMDescription
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
Occult carcinomaTX, N0, M0TX = 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.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 3. Definitions of TNM Stage 0a
StageTNMDescription
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
0Tis, N0, M0Tis = Carcinoma in situ.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 4. Definitions of TNM Stage IAa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IAT1a, N0, M0T1a = Tumor ≤2 cm 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).b
Two-panel drawing of stage I non-small cell lung cancer. First panel shows stage IA with cancer (3 cm or less) in the right lung; also shown are the right main bronchus, trachea, lymph nodes, bronchioles, and diaphragm. Second panel shows stage IB with cancer (more than 3 cm but not more than 5 cm) in the left lung and in the left main bronchus; the carina is also shown. Inset shows cancer that has spread from the lung into the innermost layer of the lung lining; a rib is also shown.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T1b, N0, M0T1b = Tumor >2 cm but ≤3 cm 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).b
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 5. Definitions of TNM Stage IBa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IBT2a, N0, M0T2a = Tumor >3 cm but ≤5 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
Two-panel drawing of stage I non-small cell lung cancer. First panel shows stage IA with cancer (3 cm or less) in the right lung; also shown are the right main bronchus, trachea, lymph nodes, bronchioles, and diaphragm. Second panel shows stage IB with cancer (more than 3 cm but not more than 5 cm) in the left lung and in the left main bronchus; the carina is also shown. Inset shows cancer that has spread from the lung into the innermost layer of the lung lining; a rib is also shown.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 6. Definitions of TNM Stage IIAa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IIAT2b, N0, M0T2b = Tumor >5 cm but ≤7 cm or less in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
Two-panel drawing of stage IIA non-small cell lung cancer. First panel shows cancer (5 cm or less), and cancer in the right main bronchus and lymph nodes; also shown are the trachea, bronchioles, and diaphragm. Second panel shows cancer (more than 5 cm but not more than 7 cm), and cancer in the left main bronchus; also shown are the trachea, lymph nodes, bronchioles, and diaphragm. Insets show cancer that has spread from the lung into the innermost layer of the lung lining; a rib is also shown.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T1a, N1, M0T1a = Tumor ≤2 cm 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).b
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
T1b, N1, M0T1b = Tumor >2 cm but ≤3 cm 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).b
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
T2a, N1, M0T2a = Tumor >3 cm but ≤5 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
Table 7. Definitions of TNM Stage IIBa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IIBT2b, N1, M0T2b = Tumor >5 cm but ≤7 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
Two-panel drawing of stage IIB non-small cell lung cancer. First panel shows cancer (more than 5 cm but not more than 7 cm), and cancer in the right main bronchus and lymph nodes; also shown are the trachea, bronchioles, and diaphragm. Inset shows cancer that has spread from the lung to the innermost layer of the lung lining; a rib is also shown. Second panel shows cancer (more than 7 cm), and cancer in the left main bronchus; also shown are the trachea, lymph nodes, bronchioles, and diaphragm. Top inset shows cancer that has spread from the lung through the lung lining and chest wall lining into the chest wall; a rib is also shown. Bottom inset shows the heart and cancer that has spread from the lung into the membrane around the heart.
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
T3, N0, M0T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carinab but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe.b
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 8. Definitions of TNM Stage IIIAa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IIIAT1a, N2, M0T1a = Tumor ≤2 cm 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).b
Stage IIIA non-small cell lung cancer (1). Drawing shows cancer in lymph nodes, left main bronchus, and diaphragm; there may be separate tumors in the same lung; the trachea is also shown. Top inset shows cancer that has spread from the lung through the lung lining and chest wall lining into the chest wall; a rib is also shown. Bottom inset shows the heart and cancer that has spread from the lung into the membrane around the heart.
Stage IIIA lung cancer (2). Drawing shows cancer in the lymph nodes, trachea, carina, left main bronchus, esophagus, sternum, diaphragm, and major blood vessels that lead to or from the heart; there may be separate tumors in the same lung. Top inset shows cancer that has spread from the lung through the lung lining and chest wall lining into the chest wall; a rib is also shown. Bottom inset shows cancer that has spread from the lung, through the membrane around the heart, into the heart.
Stage IIIA non-small cell lung cancer (3). Drawing shows cancer in the heart, major blood vessels that lead to or from the heart, the trachea, esophagus, sternum, and carina; the diaphragm is also shown. Inset shows cancer that has spread from the lung, through the membrane around the heart, into the heart.
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T1b, N2, M0T1b = Tumor >2 cm but ≤3 cm 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).b
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T2a, N2, M0T2a = Tumor >3 cm but ≤5 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T2b, N2, M0T2b = Tumor >5 cm but ≤7 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T3, N1, M0T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carinab but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe.
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
T3, N2, M0T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carinab but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe.
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T4, N0, M0T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T4, N1, M0T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
M0 = No distant metastasis.
Table 9. Definitions of TNM Stage IIIBa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
IIIBT1a, N3, M0T1a = Tumor ≤2 cm 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).b
Stage IIIB non-small cell lung cancer (1). Drawing shows cancer in lymph nodes above the collarbone on the opposite side of the chest as the primary tumor, and in the trachea, carina, left main bronchus, esophagus, sternum, diaphragm, and major blood vessels that lead to or from the heart; there may be separate tumors in the same lung. Top inset shows cancer that has spread from the lung, through the lung lining and chest wall lining, into the chest wall; a rib is also shown. Bottom inset shows cancer that has spread from the lung, through the membrane around the heart, into the heart.
Stage IIIB non-small cell lung cancer (2). Drawing shows cancer in lymph nodes on the same side of the chest as the primary tumor, in the heart, major blood vessels that lead to or from the heart, the trachea, esophagus, sternum, carina, and in separate tumors in different lobes of the same lung; the diaphragm is also shown. Inset shows cancer that has spread from the lung, through the membrane around the heart, into the heart.
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
T1b, N3, M0T1b = Tumor >2 cm but ≤3 cm 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).b
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
T2a, N3, M0T2a = Tumor >3 cm but ≤5 cm or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
T2b, N3, M0T2b = Tumor >5 cm but ≤7 cm or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
T3, N3, M0T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carinab but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe.
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
T4, N2, M0T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
M0 = No distant metastasis.
T4, N3, M0T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
M0 = No distant metastasis.
Table 10. Definitions of TNM Stage IVa
StageTNMDescriptionIllustration
aReprinted with permission from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 253-70.
bThe uncommon superficial spreading of the tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus, is also classified as T1a.
cMost pleural (and pericardial) effusions with lung cancer are due to tumor. In a few patients, however, multiple cytopathologic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and is not an exudate. Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element, and the patient should be classified as M0.
IVAny T, Any N, M1a OR Any T, Any N, M1bTX = 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.
Stage IV non-small cell lung cancer. Drawing shows other parts of the body where lung cancer may spread, including the other lung, the brain, lymph nodes, adrenal gland, kidney, liver, and bone. Inset shows cancer spreading through the blood and lymph nodes to other parts of the body.
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 (i.e., not in the main bronchus).b
T2 = Tumor >3 cm but ≤7 cm in greatest dimension, or tumor with any of the following features (T2 tumors with these features are classified T2a if ≤5 cm): involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carinab but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe.
T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including 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).
M0 = No distant metastasis.
M1 = Distant metastasis.
M1a = Separate tumor nodule(s) in a contralateral lobe tumor with pleural nodules or malignant pleural (or pericardial) effusion.c
M1b = Distant metastasis (in extrathoracic organs).

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  • Updated: August 6, 2014