Limited-Stage Disease
Extensive-Stage Disease
Other Staging and Prognostic Factors

Staging procedures for small cell lung cancer (SCLC) are important in distinguishing patients with disease limited to their thorax from those with distant metastases. Determining the stage of cancer allows an assessment of prognosis and a determination of treatment, particularly when chest radiation therapy or surgical excision is added to chemotherapy for patients with limited-stage disease (LD). If extensive-stage disease (ED) is confirmed, further evaluation should be individualized according to the signs and symptoms unique to the individual patient. Standard staging procedures include:

• A thorough physical examination.
• Routine blood counts and serum chemistries.
• Chest and upper abdominal computed tomography (CT) scanning.
• A radionuclide bone scan.
• A brain magnetic resonance imaging (MRI) scan or CT scan.
• Bone marrow aspirate or biopsy in selected patients where treatment would change based on the results.

LD SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. No universally accepted definition of this term is available, and patients with pleural effusion, massive pulmonary tumor, and contralateral supraclavicular nodes have been both included within and excluded from LD by various groups. Patients with pleural effusion have an intermediate prognosis between LD and ED with hematogenous metastases and will be classified as having M1 disease (or ED).

ED SCLC has spread beyond the supraclavicular areas and is too widespread to be included within the definition of LD. Patients with distant metastases (M1) are always considered to have ED.[1-3]

The role of positron emission tomography (PET) is still in evolution. SCLC is fluorodeoxyglucose avid at the primary site and at metastatic sites. The largest experience to date evaluated 120 patients with LD SCLC or ED SCLC.[4] Eight percent of patients were upstaged, and 2.3% of patients were downstaged. PET was more sensitive and specific than CT scans for non-brain distant metastases. In a small series of 24 patients with LD by conventional staging, 8.3% of patients were upstaged to ED.[5] Unsuspected nodal metastases were documented in 25% of patients, which altered the radiation plan in these patients. At this time, sensitivity, specificity, and positive- or negative-predictive value of PET scanning and its enhancement staging accuracy is uncertain.

At the time of initial diagnosis, approximately two-thirds of patients with SCLC have clinical evidence of metastases; most of the remaining patients have clinical evidence of extensive nodal involvement in the hilar, mediastinal, and sometimes supraclavicular regions. Although tumor, node, metastasis (TNM) staging has been applied in small series of patients with SCLC treated either with surgery alone or with combined modality therapy including surgery, a simpler staging system based on the anatomical extent of the disease as proposed originally by the Veterans Administration Lung Study Group (VALG) is commonly used to determine if patients have LD or ED.[5] In the VALG staging system, LD is defined as disease confined to one hemithorax, which can be safely encompassed within a tolerable radiation field. Patients with LD are treated with chemotherapy and thoracic radiation, whereas, for the most part, patients with ED (distant hematogenous metastases) receive only chemotherapy.

The International Association for the Study of Lung Cancer (IASLC) revised the VALG classification [5] in accordance with the TNM system.[6] In the IASLC system, the LD definition is consistent with TNM stages I to IIIB, and ED is limited to patients with distant metastases. According to the 1989 IASLC staging system for SCLC, ipsilateral and contralateral supraclavicular nodes and hilar or mediastinal nodes are included in LD. However, in the era of conformal techniques and increasing radiation dose for SCLC, it is likely no longer appropriate to treat all patients with LD in the same way, and radiation fields may be determined using more precise nodal categories. The IASLC conducted an analysis of clinical TNM staging for SCLC using the sixth edition of TNM staging system for lung cancer.[3] Survivals for patients with clinical stages I and II are significantly different from those of stage III with N2 or N3 involvement.[2] Patients with pleural effusion have an intermediate prognosis between LD and ED with hematogenous metastases and will be classified as having M1 disease (or ED). The analysis suggests that, in the context of clinical trials in LD, accurate TNM staging may be critical and stratification based on TNM stage may be important.[2]

References

1. Ihde D, Souhami B, Comis R, et al.: Small cell lung cancer. Lung Cancer 17 (Suppl 1): S19-21, 1997.  [PUBMED Abstract]
   
   
2. Shepherd FA, Crowley J, Van Houtte P, et al.: The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol 2 (12): 1067-77, 2007.  [PUBMED Abstract]
   
   
3. Mountain CF: Revisions in the International System for Staging Lung Cancer. Chest 111 (6): 1710-7, 1997.  [PUBMED Abstract]
   
   
4. Brink I, Schumacher T, Mix M, et al.: Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer. Eur J Nucl Med Mol Imaging 31 (12): 1614-20, 2004.  [PUBMED Abstract]
   
   
5. Bradley JD, Dehdashti F, Mintun MA, et al.: Positron emission tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol 22 (16): 3248-54, 2004.  [PUBMED Abstract]
   
   
6. Stahel R, Ginsberg R, Havemann K, et al.: Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer 5 (4-6): 119-26, 1989. 
   
   

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