Surgery Reconsidered

As experience with chemotherapy began to accrue, consideration of surgical treatment for small cell lung cancer resurfaced, this time as an adjuvant to induction chemotherapy.(10)

Being a local treatment, surgical removal of the primary site and regional lymph nodes would be able to control the residual disease in the chest once the metastatic problem was controlled by systemic therapy. An advantage of this approach was believed to be the ability to avoid the combination of chemotherapy (especially, doxorubicin-based regimens) and thoracic irradiation, since such a combination was fraught with considerable mediastinal and pulmonary toxicity. During the 1980s, a small number of phase II uncontrolled experiences were published in which selected groups of patients were submitted for pulmonary resection after chemotherapy.(10-15) Table 10–1 summarizes these experiences. These were heterogeneous groups of patients with a variety of preoperative chemotherapy exposures selected from various populations of small cell lung cancer patients. Despite the heterogeneity, some of the clinical observations were similar. Removal of the tumor often required pneumonectomy. Resectability rates were high but lower than one would expect in a non–small cell population of similar clinical stages. The pathologic complete response rate to chemotherapy was in the teens, and residual non–small cell histologies were discovered in an appreciable portion of patients. Local recurrence rates, when specified, were low. A common feature of all of these experiences was that the prerequisite to pulmonary resection was favorable response (tumor shrinkage) to preoperative chemotherapy.

For the sake of comparison, Table 10–2 lists four large surgical series of lung cancer patients predating the chemotherapy era.(16-19) These four series comprise 3150, 3660, 1820, and 1800 patients, respectively, and report outcomes for a total of 448 resected small cell lung cancer patients (4.3% of the total number of lung cancers). This table seems to indicate that there is a population of patients with small cell lung cancer that has low-stage disease and does well even without chemotherapy. Expanding upon this type of observation, another combined modality strategy has been to use surgery as initial treatment for patients with low clinical stage (i.e., stage I), and deliver systemic therapy as a postoperative adjuvant. This strategy became more tenable as imaging technology improved and allowed for more sensitive preoperative staging to be accomplished. Table 10–3 summarizes a number of such reports. 15, 20–24

In this series of observations, the outcomes were good, except for the first citation on the table. The majority of these patients were in stage I at the time of initial treatment and are thereby in a select group, since small cell lung cancer usually arises in large central airways and mediastinal node metastases are usually present.

Reference to Table 10–2 illustrates this point when one considers that the denominator for the 448 patients in the first three series totaled over 10, 400 patients.