The New International Staging System for Lung Cancer

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Surgical Treatment of Lung Carcinoma

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The New International Staging System for Lung Cancer Clifton F. Mountain, M.D. *

The new International Staging System for Lung Cancer provides a nomenclature for disease extent that has consistent meaning among specialists and countries throughout the world. This system is based on the TNM classification principles (T, primary tumor; N, regional lymph nodes; M, distant metastasis) initially proposed by Denoix2 and subsequently applied by the International Union Against Cancer (UICe) and the American Joint Committee on Cancer (AJCe). The international system retains many of the valid and useful elements of the earlier staging recommendations of both of these groups. I, 3 It has new elements structured to resolve staging problems with prior recommendations and to meet the needs of contemporary treatment planning. The views culminating in this system are based on the collective experience of several centers and users of the TNM system in North America, Europe, and Japan. TNM DEFINITIONS Primary Tumor Descriptors The International Staging System provides for classification of four distinct levels of primary tumor progression, T1, T2, T3 and T4, each having specific implications for treatment selection and survival. The descriptors for T1 and T2 remain the same as in prior staging recommendations of the UICC 3 and the AJCC I but there are new definitions for T3 and T4 categories (Table 1). *Professor of Surgery, Department of Thoracic Surgery, the University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas This project was supported by the following foundations, private donors, and government agencies: American Joint Committee on Cancer, Hawn Foundation of Texas, Herman Neel Hipp Fund for Research in Thoracic Surgery, Kelsey-Seybold Foundation grant 996, National Cancer Institute Division of Cancer Treatment (contract CA 34503 to Reference Center for Anatomic and Pathologic Classification of Lung Cancer of the Lung Cancer Study Group), and Private Donors Fund for Research in Thoracic Surgery (Department of Thoracic Surgery, University of Texas System Cancer Center M. D. Anderson Hospital).

Surgical Clinics of North America-Vol. 67, No.5, October 1987

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Table 1. New International Staging System for Lung Cancer: TNM Definitions Primary tumor (T)

TX

Tumor proven by the presence of malignant cells in bronchopulmonary secretions but not visualized by roentgenography or bronchoscopy, or any tumor that cannot be assessed as in a retreatment staging. No evidence of primary tumor. TO Carcinoma in situ. TIS A tumor that is 3.0 cm or less in greatest dimension, surrounded by Tl lung or visceral pleura, and without evidence of invasion proximal to a lobar bronchus at bronchoscopy. * A tumor more than 3.0 cm in greatest dimension, or a tumor of any T2 size that either invades the visceral pleura or has associated atelectasis or obstructive pneumonitis extending to the hilar region. At bronchoscopy, the proximal extent of demonstrable tumor must be within a lobar bronchus or at least 2.0 cm distal to the carina. Any associated atelectasis or obstructive penumonitis must involve less than an entire lung. A tumor of any size with direct extension into the chest wall T3 (including superior sulcus tumors), diaphragm, or the mediastinal pleura or pericardium without involving the heart, great vessels, trachea, esophagus, or vertebral body, or a tumor in the main bronchus within 2.0 cm of the carina without involving the carina. A tumor of any size with invasion of the mediastinum or involving T4 heart, great vessels, trachea, esophagus, vertebral body, or carina or with presence of malignant pleural effusion. t Nodal involvement (N) NO No demonstrable metastasis to regional lymph nodes. Nl Metastasis to lymph nodes in the peribronchial or the ipsilateral hilar region, or both, including direct extension. Metastasis to ipsilateral mediastinal lymph nodes and subcarinal N2 lymph nodes. Metastasis to contralateral mediastinal lymph nodes, contralateral N3 hilar lymph nodes, or ipsilateral or contralateral scalene or supraclavicular lymph nodes. Distant metastasis (M) MO No (known) distant metastasis. Ml Distant metastasis present-specifY site(s). *The uncommon superficial tumor of any size whose invasive component is limited to the bronchial wall and that may extend proximal to the main bronchus is classified as Tl. tMost 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 and the fluid is nonbloody and is not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the cases should be staged Tl, T2, or T3, with effusion being excluded as a staging element.

Tl. Tumor size and location are important characteristics of the Tl descriptor. This category includes only tumors equal to or less than 3 cm. There can be no tumor involvement proximal to a lobar bronchus or involvement of the pleura. The footnote in Table 1 is included with the new staging schema to aid in the assignment ofTl disea£e for the uncommon superficial tumor that may involve the main bronchus but has no invasion beyond the bronchial wall. T2. The T2 category reflects the influence on survival of increasing tumor size, involvement of the visceral pleura or the main bronchus, and

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the effect of complications such as atelectasis or obstructive pneumonitis involving the hilum. T3. The new T3 category identifies patients with limited, circumscribed, extrapulmonary tumors that, generally, are considered resectable. Peripheral tumors invading the chest wall, superior sulcus tumors with no invasion of the vertebral body or Pancoast syndrome (Figs. 1 and 2), and tumors with direct extension involving the pericardium are classified as T3. T4. The T4 descriptor identifies tumors with extensive involvement of the mediastinal structures that is usually considered uuresectable. Patients with superior vena caval syndrome (Fig. 3) and those with Pancoast tumors with unresectable involvement of the vertebral body (Fig. 4) are classified as having T4 tumors. The vast majority of patients with lung cancer involving the carina have unresectable disease, and their tumors are classified T4. There are a few patients with biologically favorable tumors arising in or involving the carina that are amenable to tracheobronchial resection and reconstruction; however, the T4 category has not been subdivided to account for this small group. Tumors are classified T4 if they involve the carina. Implications of Pleural Effusion. Clinical evidence of pleural effusion in patients with lung cancer usually predicts unresectability and a poor prognosis, regardless of the presence or absence of malignant cells in the fluid. For this reason nearly all patients with fluid in the chest are classified as having T4 tumors. There are, however, a few patients in whom clinical judgment and multiple negative cytology reports indicate that the effusion is unrelated to the tumor. A footnote is included with the classification (see Table 1) to aid in the assignment of T1, T2, or T3 to these cases, in which the effusion is disregarded as a staging element.

Figure 1. T3: A tumor of any size with direct extension into the chest wall (a), including superior sulcus tumors (b). (From Mountain CF: A new international staging system for lung cancer. Chest 89:225S-233S, 1986; with permission.)

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Esophagus Trachea Lung (apex of upper lobe)

T3

Rib II

Rib II (head and thoracic ganglion)

Thoracic vertebra II (spinous proc.)

Figure 2. T3: Superior sulcus tumor with no involvement of the vertebral body. (From Mountain CF: A new international staging system for lung cancer. Chest 89:225S-233S, 1986; with permission.)

Figure 3. T4: Superior vena cava syndrome, with tumor involving the great vessels. (From Mountain CF: A new international staging system for lung cancer. Chest 89:225S-

233S, 1986; with permission.)

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Rib II

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Rib II (head and thoracic ganglion)

Thoracic vertebra II (spinous proc.

Figure 4. T4: Tumor invading the vertebral body. Tumor is unresectable and produce, Pancoast syndrome. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2255-2335, 1986; with permission.)

Regional Lymph Node Descriptors The International Staging System provides for classifying three levels of lymph node involvement that relate to therapeutic options and planning. The descriptor for Nl disease remains the same as in prior UICC 3 and AJCC l staging recommendations; however, new definitions for the N2 descriptor and for an N3 category are provided (see Table 1). These descriptors resolve the problems of distinguishing patients with metastases limited to the ipsilateral mediastinal nodes from those with more extensive involvement, and of including the supraclavicular!scalene nodes as regional disease. The N3 descriptor enables more specific classification and reproducibility of groups designated as having "limited" or "extensive" disease. Nl. The Nl category describes lymph node metastases, or involvement by direct extension, that are confined to the intrapulmonary lymph nodes; this includes the hilar and peribronchial nodes-lobar, interlobar, and segmental. N2. Lymph node metastases limited to the ipsilateral mediastinal and subcarinal nodes are classified as N2 (Fig. 5). This new descriptor does not represent a change in the classification of surgical patients, whose N2 status has always been confined to the ipsilateral mediastinal and subcarinal nodes. For patients with inoperable metastases who are given other therapies, the designation provides for separation of patients with locally advanced disease into categories for treatment planning. N3. The N3 category designates metastases to the contralateral mediastinal and hilar nodes and the ipsilateral and contralateral supraclavicular! scalene nodes (Fig. 6). This new descriptor enables classification of these nodal groups as regional disease, which is consistent with the structuring of treatment plans for this extent of disease.

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Figure 5. N2: Involvement of ipsilateral mediastinal and/or subcarinallymph nodes. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2258-2338, 1986; with permission.)

N3 Involvement of contralateral ~~~~~. or ipsilateral supraclavicular/scalene lymph nodes.

N3-----Involvement of contralateral mediastinal or contralateral hilar lymph nodes

N3 Figure 6. N3: Involvement of contralateral or ipsilateral scalene or supraclavicular lymph nodes or of contralateral mediastinal or contralateral hilar lymph nodes. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2258-2338, 1986; with permission.)

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Descriptor for Distant Metastases Ml. Metastases to distant organ or lymph node sites are classified as Ml disease.

STAGE GROUPING Stage grouping of the TNM subsets is shown in Table 2. Patients with occult carcinoma are classified as TXNOMO, and a stage classification is not assigned to them. The assignment of Stage 0 to patients with carcinoma in situ is consistent with the staging rules for other sites of cancer. Stage I Stage I identifies patients with the best prognoses. The disease is completely contained within the lung, and there is no evidence of lymph node or other metastases. This group with TINOMO and T2NOMO tumors are the optimum candidates for definitive surgical treatment, and a very favorable outcome is anticipated for them (Fig. 7). Stage II In patients with Stage II disease, the lung cancer is completely contained within the lung; however, in all of these patients the tumor has progressed to involve the intrapulmonary lymph nodes, by either metastasis or direct extension. Stage II includes two anatomic subsets, TINIMO and T2NIMO disease (Fig. 8). Stage III This stage group includes patients with extrapulmonary extension of the primary tumor and regional lymph node metastases. Stage III excludes patients with distal metastatic disease. It is subdivided into "a" and "b" categories to distinguish patients with limited extrapulmonary extension and metastases from those with more extensive spread of the disease. Stage Illa. This designation identifies patients with limited, circumscribed extrapulmonary extension of the primary tumor and metastases confined to the ipsilateral mediastinal and subcarinal lymph nodes-the T3NO-NIMO and Tl-3N2MO ,subsets (Fig. 9). Stage IlIa identifies patients

Table 2. New International Staging System for Lung Cancer: Stage Grouping Occult carcinoma Stage 0 Stage I Stage II Stage lIla Stage IIIb Stage IV

TX

NO Carcinoma in Tl NO T2 NO Tl Nl T2 Nl T3 NO Tl-3 N2 AnyT N3 T4 AnyN AnyT AnyN

MO situ MO MO MO MO MO MO MO MO Ml

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T1 NO MO

T2 NO MO Involving mainstem bronchus>2 cm. distal to carina

T2 NO MO Involving visceral pleura

Stage I No Lymph Node Involvement

Figure 7. 8tage I disease. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2258-2338, 1986; with permission.)

T2 N1

M()---"

T2 N1 MO

S 3 cm. involving peribronchial lymph nodes (by direct extension)

Stage II (Intrapulmonary andlor Hilar Nodes Involved)

Figure 8. 8tage II disease. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2258-2338, 1986; with permission.)

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T3 NO MO T2 N2 MO >3 cm. tumor involving ipsi lateral hilar and mediastinal lymph nodes

T3 N1 MO Peripheral tumor involving chest wall and intrapulmonary lymph nodes

Stage III-a Figure 9. 5tage Ilia disease. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2255-2335, 1986; with permission.)

Involvement of mediastinum, (ipsilateral and) contralateral mediastinal lymph nodes, contralateral hilar nodes, supraclavicular lymph nodes

Stage 111- b Figure lO. 5tage I1Ib disease. (From Mountain CF: A new international staging system for lung cancer. Chest 89:2255-2335, 1986; with permission.)

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with extrapulmonary disease who are candidates for definitive surgical treatment. All patients assigned to Stage lIla will not be candidates for operation; however, the classification provides for identifying a level of disease extent that relates to prognosis, definitive radiotherapy planning factors, and other treatment assignments. Stage Illb. Patients with more extensive involvement of mediastinal structures than described for the Stage IlIa group, and metastases to contralateral mediastinal, contralateral hilar and ipsilateral, or contralateral supraclavicular/scalene lymph nodes, are assigned to Stage IIIb. This group includes patients with T4AnyNMO and AnyTN3MO disease (Fig. 10). These patients are generally given nonsurgical therapies. Stage IV All patients with evidence of distant metastases, AnyTAnyNM1, are classified as having Stage IV disease.

SUMMARY The International Staging System for Lung Cancer provides for classification of six levels of disease extent in five stage groups that relate to patient management and prognosis. Stage 0 is reserved for patients with carcinoma in situ. The Stage I and II definitions provide for classification of two levels of disease extent completely contained within the lung that have different prognostic and therapeutic implications. Definitive resection is the first choice of therapy for patients with non-small cell lung cancer in these stage groups. The Stage II category takes into account the erosion of survival expectations in the optimum group of T1 and T2 patients as a consequence of intrapulmonary lymph node involvement. 4 Although small cell carcinoma is infrequently encountered as Stage I and Stage II disease, these classifications may be useful in the structure of investigational programs involving adjuvant surgery. The exclusion of distant metastases and the division of Stage III into two levels of extrapulmonary disease allow for selection of patients for specific treatment plans. Patients with non-small cell tumors with Stage IlIa disease usually are candidates for definitive surgical treatment. The specificity of the T and N definitions in the Stage lIla and Illb categories identifies patients for whom particular radiotherapy treatment plans are structured and protocol assignments are made. It is consistent with patient management concepts that all those with distant metastases are classified as haVing Stage IV disease. Implications of the system for selection of surgical, radiotherapeutic, and chemotherapeutic regimens are rational for all cell types. The classification meets the requirement for simplicity and can be readily applied in a broad spectrum of clinical and teaching environments. It is, however, sufficiently specific to be useful for reporting results of investigational therapies. Prospective use of the classification should encourage precision in clinical evaluations that exploit full use of refinements in imaging technologies.

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The cooperative efforts of the Task Force on Lung of the AJCC and the TNM Committees of the VICC to bring this classification system to fruition and international acceptance have been described. 5 It has been adopted by these groups and others, including the International Association for the Study of Lung Cancer, the Japanese Cancer Committee, and the Spanish Society of Respiratory Disease, as their official recommendation for staging lung cancer.

REFERENCES 1. American Joint Committee on Cancer, Task Force on Lung: Staging of Lung Cancer 1979. Chicago, American Joint Committee on Cancer, 1979 2. Denoix PF: Enquete permanent dans les centres anticancereux. Bull Inst Natl Hyg 1:7075, 1946 3. Harmer EM: TNM Classification of Malignant Tumors. Geneva, Union Internationale Contre Ie Cancer, 1978, pp 41-45 4. Martini N, Flehinger BJ, Nagasaki F: Prognostic significance of Nl disease in carcinoma of the lung. J Thorac Cardiovasc Surg 86:646-653, 1983 5. Mountain CF: A new international staging system for lung cancer. Chest 89:225S-233S, 1986 Department of Thoracic Surgery The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute Texas Medical Center 6723 Bertner Avenue Houston, Texas 77030