Small cell carcinoma

Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival. With incorporation of current chemotherapy regimens into the treatment program, however, survival is unequivocally prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. Furthermore, about 10% of the total population of patients remains free of disease over 2 years from the start of therapy, the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small and non-small cell types). The overall survival at 5 years is 5% to 10%.

Limited-stage disease - At the time of diagnosis, approximately 30% of patients with small cell carcinoma will have tumor confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes. These patients are designated as having limited-stage disease, and most 2-year disease-free survivors come from this group. In limited-stage disease, median survival of 16 to 24 months with current forms of treatment can reasonably be expected.[6-8] A small proportion of patients with limited-stage disease may benefit from surgery with or without adjuvant chemotherapy; these patients have an even better prognosis.

Extensive stage disease - Patients with tumors that have spread beyond the supraclavicular areas are said to have extensive-stage disease and have a worse prognosis than patients with limited-stage disease. Median survival of 6 to 12 months is reported with currently available therapy, but long-term disease-free survival is rare.

The pretreatment prognostic factors that consistently predict for prolonged survival include good performance status, female gender, and limited-stage disease. Patients with involvement of the central nervous system or liver at the time of diagnosis have a significantly worse outcome. In general, patients who are confined to bed tolerate aggressive forms of treatment poorly, have increased morbidity, and rarely attain 2-year disease-free survival; however, patients with poor performance status can often derive significant palliative benefit and prolongation of survival from treatment.

Regardless of stage, the current prognosis for patients with small cell lung cancer is unsatisfactory even though considerable improvements in diagnosis and therapy have been made over the past 10 to 15 years. All patients with this type of cancer may appropriately be considered for inclusion in clinical trials at the time of diagnosis. Information about ongoing clinical trials is available from the NCI Web site.

Review of pathologic material by an experienced lung cancer pathologist is important prior to initiating treatment of any patient with small cell lung cancer. The intermediate subtype of small cell carcinoma and the more readily recognized lymphocyte-like or oat cell subtype are equally responsive to treatment.

• Small cell carcinoma.
• Mixed small cell/large cell carcinoma.
• Combined small cell carcinoma (i.e., small cell lung cancer combined with neoplastic squamous and/or glandular components).

Neuroendocrine carcinomas of the lung represent a spectrum of disease. At one extreme is small cell lung cancer, which has a poor prognosis. At the other extreme are bronchial carcinoids, which have an excellent prognosis after surgical excision. Between these extremes is an unusual entity called well-differentiated neuroendocrine carcinoma of the lung.[3] It has been referred to as malignant carcinoid, metastasizing bronchial adenoma, pleomorphic carcinoid, nonbenign carcinoid tumor, and atypical carcinoid. Like small cell lung cancer, it occurs primarily in cigarette smokers, but it metastasizes less frequently. The 5-year survival rate is >50% in some series, and surgical cure appears possible in most stage I patients. Careful diagnosis is important, however, since the differential pathologic diagnosis from small cell lung cancer may be difficult.