Clinical benefits of perioperative chemotherapy for patients with stage I-II large cell lung cancer: A SEER database analysis

Background: Large cell lung cancer (LCLC), a neuroendocrine subtype of non-small cell lung cancer, remains an aggressive malignancy with limited therapeutic options. Even early-stage disease shows high recurrence rates and suboptimal survival after resection. Evidence guiding the role of perioperative chemotherapy (CTx) in stage I-II LCLC is limited. This study evaluated the association between perioperative CTx and survival outcomes in surgically resected LCLC using a nationally representative dataset. Methods: Patients with stage I-II LCLC diagnosed between 2000-2021 were identified from the Surveillance, Epidemiology, and End Results Program (SEER) 17 registries. Inclusion criteria were pathologically confirmed LCLC, surgical resection, and American Joint Committee on Cancer (AJCC) 7th/8th edition staging. Demographic, clinicopathologic, and socioeconomic variables were collected. Overall survival (OS) and cancer-specific survival (CSS) were compared between surgery alone and surgery plus perioperative CTx using Kaplan-Meier analysis. Multivariable Cox regression was performed to identify independent predictors of CSS among stage II LCLC. Results: A total of 1,894 patients met inclusion criteria, including 489 who received neoadjuvant and/or adjuvant CTx . Patients receiving neoadjuvant and/or adjuvant CTx were younger (median 65 vs. 70 years, p<0.001), had more advanced T and N stages, and more frequently had advanced stages (p<0.001). Socioeconomic factors were not significantly different between groups. Perioperative CTx was significantly associated with improved CSS (Hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.60-0.85, p<0.001) and OS (HR 0.67, 95% CI 0.58-0.78, p<0.001) with a more pronounced benefit among patients with nodal involvement. On multivariable analysis among stage II LCLC, perioperative CTx independently predicted better CSS (HR 0.79, 95% CI 0.57-0.86, p<0.001); age over 75 (HR 1.76), male sex (HR 1.26), and N1 nodal status (HR 2.10) were also associated with higher mortality. Conclusions: In this large SEER cohort, neoadjuvant and/or adjuvant chemotherapy was associated with significantly improved cancer-specific survival in patients with resected stage I-II LCLC, with the greatest benefit observed among patients with nodal disease. Although information on surgical extent and mediastinal lymph node dissection was limited, these findings support consideration of perioperative CTx for early-stage LCLC and underscore the need for prospective studies to define optimal treatment strategies.