General Medical Information

Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of at least 3 distinct histologies of lung cancer including epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. These histologies are often classified together because, when localized, all have the potential for cure with surgical resection. Systemic chemotherapy can produce objective partial responses and palliation of symptoms for short durations in patients with advanced disease. Local control can be achieved with radiation in a large number of patients with unresectable disease, but cure is seen only in a small minority of patients.

At diagnosis, patients with NSCLC can be divided into 3 groups that reflect the extent of disease and treatment approach:

The first group of patients has tumors that are surgically resectable (generally stages I and II). This is the group with the best prognosis, depending on a variety of tumor and host factors. Patients with resectable disease who have medical contraindications to surgery can be considered for curative radiation therapy.

The second group includes patients with either locally (T3-T4) or regionally (N2-N3) advanced lung cancer who have a diverse natural history. This group is treated with radiation therapy or, more commonly, with radiation therapy in combination with chemotherapy or other therapy modalities. Selected patients with T3 or N2 disease can be treated effectively with surgical resection alone.

The final group of patients have distant metastases (M1) found at the time of diagnosis. This group can 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 appear to live longer than others.[1] Cisplatin-based chemotherapy has been associated with short-term palliation of symptoms and a small survival advantage. Currently no single chemotherapy regimen can be recommended for routine use.

For patients with operable disease, prognosis is adversely influenced by the presence of pulmonary symptoms, large tumor size (>3 centimeters), and presence of the erbB-2 oncoprotein.[1-6] Other factors that have been identified as adverse prognostic factors in some series of patients with resectable non-small cell lung cancer include mutation of the K-ras gene, vascular invasion, and increased numbers of blood vessels in the tumor specimen.[3,7,8]

For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of greater than 10%. In multiple retrospective analyses of clinical trial data, advanced age alone has not been shown to influence response or survival with therapy.[9]

Since treatment is not satisfactory for almost all patients with NSCLC, with the possible exception of a subset of patients with pathologic stage I (T1, N0, M0) disease treated surgically, eligible patients should be considered for clinical trials.

References

1. Albain KS, Crowley JJ, LeBlanc M, et al.: Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 9 (9): 1618-26, 1991.

2. Macchiarini P, Fontanini G, Hardin MJ, et al.: Blood vessel invasion by tumor cells predicts recurrence in completely resected T1 N0 M0 non-small-cell lung cancer. J Thorac Cardiovasc Surg 106 (1): 80-9, 1993.

3. Harpole DH, Herndon JE, Wolfe WG, et al.: A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res 55 (1): 51-6, 1995.

4. Ichinose Y, Yano T, Asoh H, et al.: Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg 110 (3): 601-5, 1995.

5. Martini N, Bains MS, Burt ME, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109 (1): 120-9, 1995.

6. Strauss GM, Kwiatkowski DJ, Harpole DH, et al.: Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung. J Clin Oncol 13 (5): 1265-79, 1995.

7. Slebos RJ, Kibbelaar RE, Dalesio O, et al.: K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323 (9): 561-5, 1990.

8. Fontanini G, Bigini D, Vignati S, et al.: Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol 177 (1): 57-63, 1995.

9. Earle CC, Tsai JS, Gelber RD, et al.: Effectiveness of chemotherapy for advanced lung cancer in the elderly: instrumental variable and propensity analysis. J Clin Oncol 19 (4): 1064-70, 2001.