Effect of neoadjuvant vs. adjuvant systemic therapy on survival in patients with surgical resected limited stage small-cell lung cancer: a real-world retrospective cohort study from SEER database

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Background: The role of neoadjuvant systemic therapy in limited-stage small cell lung cancer (SCLC) is unknown but promising. This real-world study aimed to investigate the prospects of applying neoadjuvant treatment in patients with resectable limited-stage SCLC. Methods: Patients diagnosed with stage I-III SCLC who underwent surgical resection of primary tumor were identified in the Surveillance, Epidemiology, and End Results (SEER) database (2007-2021). Survival outcomes were compared between neoadjuvant and adjuvant cohorts before and after matching. Multivariate Cox and Fine and Gray's competing risk regression models were built to identify prognostic factors and to adjust for covariates in subgroup analyses. Results: A total of 1,702 surgical resected SCLC were included in the study, among which 1,132 (67%) were treated with adjuvant therapy, while 55 (3%) received neoadjuvant therapy. Compared to adjuvant therapy, patients who received neoadjuvant therapy were significantly younger but exhibited more advanced tumor stages. In entire cohort, multivariate analyses showed that neoadjuvant therapy was independent favorable prognostic factor for overall survival (OS) [hazard ratio (HR) =0.69, 95% confidence interval (CI): 0.48-0.99, P=0.04]; however, the mortality reduction for lung cancer-specific survival (LCSS) was not significant [subdistribution hazard ratio (SHR) =0.83, 95% CI: 0.56-1.23, P=0.35]. Subgroup analyses indicated that patients with more advanced tumor stages tended to derive greater survival benefits from neoadjuvant systemic therapy. In matched cohort, neoadjuvant therapy was significantly associated with both improved OS (log-rank P=0.04) and LCSS (Fine and Gray's P=0.04) in stage III cohort. Conclusions: In the real world, neoadjuvant systemic therapy was associated with improved survival in surgical resected SCLC, especially for those with stage III disease. This indicates that neoadjuvant therapy might be a promising treatment modality for resectable locally advanced SCLC.

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