Surgery Versus Chemotherapy and Radiotherapy For Early and Locally Advanced Small Cell Lung Cancer: A Propensity-Matched Analysis of Survival

Background: The role of surgery in small cell lung cancer (SCLC) is controversial. Survival outcomes for resection of stage I-IIIA SCLC compared to chemotherapy-based non-surgical treatment (NST) were examined using propensity matching.

Methods: 29,994 clinical stage I-IIIA SCLC patients, including 2,619 undergoing surgery, were identified in the National Cancer Database. Stage-specific propensity scores for receipt of surgery were created. Resected patients were matched 1:1 to those undergoing NST. Overall survival (OS) was assessed using Kaplan-Meier and multivariable Cox models. A separate match was performed comparing Stage I/II patients aged <85 with a Charlson score of 0 who underwent lobectomy with adjuvant chemotherapy (and radiotherapy if node positive) to those treated with multiagent chemotherapy and concurrent chest radiotherapy (CRT) of at least 40 gray.

Results: 2,089 patients were matched, and cohorts were well balanced. Surgery was associated with longer survival for Stage I (median OS 38.6 months vs. 22.9 months, HR 0.62 95%CI 0.57-0.69, p<0.0001), but survival differences were attenuated for Stage II (median OS 23.4 months vs. 20.7 months, HR 0.84 95%CI 0.70-1.01, p=0.06) and IIIA (median OS 21.7 vs. 16.0 months, HR 0.71 95%CI 0.60-0.83, p <0.0001). In analyses by T and N stage, longer OS was observed in resected patients with stage T3/T4 N0 (median OS 33.0 vs. 16.8 months, p=0.008) and node positivity(N1+ 24.4 vs. 18.3 months p=0.03; N2+ 20.1 vs. 14.6 months p=0.007). In the subgroup analysis, 507 stage I/II patients receiving lobectomy and adjuvant chemotherapy were matched to patients receiving concurrent CRT. In this cohort, lobectomy with adjuvant chemotherapy was associated with significantly longer survival (median OS 48.6 vs. 28.7 months, p<0.0001).

Conclusions: Surgical resection is associated with significantly longer survival for early SCLC. New randomized trials should assess trimodality therapy in stages I/II, and in node negative disease.