To determine the incidence of second primary cancers developing in patients surviving free of cancer for 2 or more years after treatment for small-cell lung cancer and to assess the potential effect of smoking cessation.

Retrospective review of 540 patients from a single institution with a median follow-up of 6.1 years.

A single government institution (the National Cancer Institute).

Consecutive sample of 540 patients with histologically confirmed small-cell lung cancer treated from 1973 through 1989 on therapeutic clinical trials.

The relative risk for second primary cancers and death were calculated in patients who remained free of cancer for 2 years after initiation of therapy. The relation of these end points to smoking history was also determined.

Fifty-five patients (10%) were free of cancer 2 years after initiation of therapy. Eighteen of these patients developed one or more second primary cancers, including 13 who developed second primary non-small-cell lung cancer. The risk for any second primary cancer compared with that in the general population was increased four times (relative risk, 4.4; 95% CI, 2.5-7.2), with a relative risk of a second primary non-small-cell lung cancer of 16 (CI, 8.4-27). Forty-three patients discontinued smoking within 6 months of starting treatment for small-cell lung cancer, and 12 continued to smoke. In those who stopped smoking at time of diagnosis, the relative risk of a second lung cancer was 11 (CI, 4.4 to 23), whereas, in those who continued to smoke, it was 32 (CI, 12 to 69).

Patients with small-cell lung cancer who survive cancer-free for more than 2 years have a significantly increased risk for development of a second primary smoking-related cancer. Cigarette smoking cessation after successful therapy is associated with a decrease in risk for a second smoking-related primary cancer.