Lung Cancer Workup and Staging

In 2010, the most recent year for which numbers are available, there were 201,144 new cases of lung cancer (107,164 men and 93,984 women) in the United States. With 158,248 deaths, lung cancer remains the leading cause of cancer-related deaths in both men and women. Of newly diagnosed cases, approximately 80% will be non–small cell lung cancer (NSCLC), and of these, 80% will involve metastatic or locally advanced disease. Only 20% will be in potentially surgically curable patients with early-stage disease, where complete resection yields 5-year survivals of 40% to 75%.

Careful staging of newly diagnosed lung cancer is critical for several reasons. First, determining the patient's clinical TNM ( t umor, n odes, m etastasis) stage allows appropriate therapeutic decisions to be made on the basis of the specific stage of disease. This is particularly important for locally advanced disease in which multimodality therapy (induction or adjuvant) is standard care, as well as for metastatic disease when surgery should be avoided. Second, accurate staging allows the clinician to give the patient valuable prognostic information. Third, staging allows evaluation of new therapeutic interventions, and comparison of results of treatments between studies and institutions.

There are controversies about the extent of workup, and the methods used for staging have evolved during the past decade.

The Staging System

Staging is a process through which the extent of lung cancer in a patient is determined by a combination of techniques including history, physical examination, imaging studies, and invasive procedures where appropriate. Before initiation of treatment, a clinical stage (cTNM) is generated. If surgical resection occurs, the operative findings and pathologic features determine the final pathologic stage (pTNM).

In 1974, the American Joint Committee for Cancer (AJCC) Staging developed a lung cancer staging system based on TNM descriptors. Naruke and coauthors devised the original lymph node map that placed nodes into stations on the basis of defined anatomic boundaries. This was subsequently modified for North America by the American Thoracic Society and by Mountain and Dresler. In 1986, the AJCC, International Union Against Cancer (UICC), and representatives from Japan proposed an International Staging System (ISS) for lung cancer that grouped patients with similar survival outcomes using anatomic criteria. This system was derived from analyses of a 3000-patient database at the M. D. Anderson Cancer Center (MDACC). The accuracy of the ISS was further confirmed by studies from Naruke and Watanabe. In 1997, analyses of the updated MDACC database of 5319 patients led to revision of the ISS, incorporated into the sixth edition of the AJCC and UICC staging manuals.

In 1996, the International Association for the Study of Lung Cancer (IASLC) initiated an international staging project to form the basis of the seventh edition of the TNM staging system. The goals of the project were to validate the individual T, N, and M descriptors using a larger database made up of medical and surgical patients from a wide geographic distribution. Data on 100,869 patients, including 67,725 cases of NSCLC, were submitted to the database, and several changes were proposed. The existing N descriptors were validated and not changed ( Fig. 16-1 ). For the T descriptors, size cutoffs were added to the T1 and T2 tumors, and tumors greater than 7 cm in greatest dimension were designated as T3, in light of the prognostic significance of increasing size of the primary tumor ( Table 16-1 ). Additional tumor nodules in the same lobe as the primary, previously known as “satellite nodules,” were reclassified from T4 to T3, and additional nodules in the ipsilateral lung became T4. The M descriptor was divided into M1a (for pleural metastases, malignant effusion, or contralateral pulmonary disease) and M1b (for extrathoracic metastases). After incorporating the suggested changes into TNM subsets, new stage groupings were identified that yield even distributions of overall survival among stages, particularly between stages IIA and IIB ( Table 16-2 ).

FIGURE 16-1, Regional lymph node stations for the staging of non–small cell lung cancer. Ao, Aorta; PA, pulmonary artery.

TABLE 16-1

Definitions for T, N, and M Descriptors in the Seventh Edition of the AJCC and UICC Staging Manuals

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(8):709, 2007.

T (Primary Tumor)
TX	Primary tumor cannot be assessed, or tumor is 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 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) *
T1a	Tumor ≤ 2 cm in greatest dimension
T1b	Tumor > 2 cm but ≤3 cm in greatest dimension
T2	Tumor > 3 cm but ≤7 cm 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) Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
T2a	Tumor > 3 cm but ≤5 cm in greatest dimension
T2b	Tumor > 5 cm but ≤7 cm in greatest dimension
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, parietal pericardium; or tumor in the main bronchus (<2 cm distal to the carina * ) 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, separate tumor nodule(s) in a different ipsilateral lobe
N (Regional Lymph Nodes)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastases
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)
MX	Distant metastasis cannot be assessed
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 ^†
M1b	Distant metastasis

AJCC, American Joint Committee for Cancer; UICC, International Union Against Cancer.

* The uncommon superficial spreading 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.

† Most 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.

TABLE 16-2

Descriptors, Proposed T and M Categories, and Proposed Stage Groupings *

Sixth Edition T/M Descriptor	Seventh Edition T/M	N0	N1	N2	N3
T1 (≤2 cm)	T1a	IA	IIA	IIIA	IIIB
T1 (>2-3 cm)	T1b	IA	IIA	IIIA	IIIB
T2 (≤5 cm)	T2a	IB	IIA	IIIA	IIIB
T2 (>5-7 cm)	T2b	IIA	IIB	IIIA	IIIB
T2 (>7 cm)	T3	IIB	IIIA	IIIA	IIIB
T3 invasion		IIB	IIIA	IIIA	IIIB
T4 (same lobe nodules)		IIB	IIIA	IIIA	IIIB
T4 (extension)	T4	IIIA	IIIA	IIIB	IIIB
M1 (ipsilateral lung)	T4	IIIA	IIIA	IIIB	IIIB
T4 (pleural effusion)	M1a	IV	IV	IV	IV
M1 (contralateral lung)	M1a	IV	IV	IV	IV
M1 (distant)	M1b	IV	IV	IV	IV

* These revisions were incorporated into the seventh edition of the AJCC and UICC staging manuals.

Diagnosis and Staging

Diagnosis and clinical staging begin with the initial history and physical examination. A single study may serve the dual purpose of securing a diagnosis and staging the patient. If a patient's treatment is nonsurgical or involves multimodality therapy, obtaining a tissue diagnosis prior to treatment is mandatory. If it appears that the patient's clinical stage will be most appropriately managed by surgical resection alone, tissue confirmation of malignancy can be secured either preoperatively or at the time of exploration, depending on the preference of the operating surgeon.

History and Physical Examination

Patients often come to the surgeon for evaluation with some studies already performed. However, the history and physical examination remain important in the initial evaluation. A detailed history focusing on risk factors—such as duration of cigarette smoking, exposure to asbestos and other industrial hazards, a prior history of lung cancer, and the presence of symptoms—allows the clinician to assess the likelihood of a diagnosis of lung cancer. Bach and associates showed that the duration of tobacco smoking, more so than the amount of daily usage, increases an individual's risk of developing lung cancer. The lung cancer risk associated with asbestos exposure also increases with the intensity and length of exposure, and together, tobacco use and asbestos exposure have a multiplicative effect. Symptoms, such as bone pain, hoarseness, weight loss, and neurologic changes, can indicate the presence of metastatic disease and direct further investigation.

A physical examination is also important. It provides an estimate of a patient's overall health status, which influences treatment selection. Physical findings, such as Horner syndrome, or the presence of clubbing, may support the suspicion of lung cancer. Physical examination may also demonstrate advanced disease. For example, palpation of the supraclavicular fossae can reveal lymph node metastases, and auscultation of the lung fields can identify the presence of a malignant pleural effusion.

Noninvasive Modalities

Chest Radiography

Posteroanterior and lateral chest radiographs, often done for unrelated reasons, are a common initial study in which a suspected lung cancer is identified. However, most lesions are not visible until they are at least 7 to 10 mm in diameter. A chest radiograph can localize the site of suspect lesions (central or peripheral) and the associated effects of disease, such as atelectasis, consolidation, or proximity to the pleural surface. The presence of a pleural effusion of chest wall invasion or of phrenic nerve involvement causing elevation of the hemidiaphragm may also be seen. Advanced disease may be identified in the case of rib destruction from bone metastases or synchronous lesions in the pulmonary parenchyma. Hilar and mediastinal lymph node metastasis is more difficult to identify, unless there is substantial enlargement.

Sputum Cytology

Cytologic analysis of sputum for malignant cells is a simple diagnostic technique but is rarely used in North America because of the epidemiologic shift from centrally located squamous cell to more peripherally located adenocarcinomas. However, sputum cytology is still a potentially relevant test in other parts of the world where squamous cell cancers are more common. Samples may be induced by saline nebulization or collected as a 3-day pool of sputum produced from spontaneous coughing in the morning. Based on 16 published studies of at least 50 patients each, the overall sensitivity is 66% (range, 42% to 97%) and the overall specificity is 99% (range, 68% to 100%). When sputum cytology is used for patients suspected of having lung cancer on clinical grounds, the diagnostic yield is higher, with a sensitivity of 87% and a specificity of 90%.

Low-Dose Computed Tomography

An increasing number of patients, particularly in developed countries, now have lung cancers identified by low-dose computed tomography (CT) because of the results of a large prospective U.S. randomized clinical trial. The National Lung Screening Trial (NLST) enrolled 53,454 persons at high risk (participants between ages 55 and 74 years with at least 30 pack years of smoking) for lung cancer at 33 medical centers and randomized them to undergo three annual screenings with either low-dose CT or posteroanterior chest radiography. Patients in the low-dose CT group had a significantly lower risk of death from lung cancer (20% relative risk reduction) and from any cause. The majority (63%) of lung cancers detected by low-dose CT were stage I tumors. The use of low-dose CT will likely increase in the future, largely supplanting chest radiography.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here