Efficacy and safety of radiotherapy following chemoimmunotherapy in extensive-stage small cell lung cancer: a retrospective comparative cohort study of consolidation versus salvage indications.

BACKGROUND: Chemoimmunotherapy (CIT) is the standard first-line regimen for extensive-stage small cell lung cancer (ES-SCLC), based on phase 3 trials such as IMpower133 and CASPIAN. However, these pivotal trials excluded thoracic radiotherapy (RT), and current guidelines lack clear recommendations regarding the addition of RT to CIT. Consequently, it remains uncertain whether adding local RT following first-line CIT enhances survival or distant metastasis control without exacerbating toxicity. This real-world study aimed to assess the efficacy and safety of adding local RT to first-line CIT in ES-SCLC, emphasizing the impact of RT timing (consolidation vs. salvage) on survival outcomes. METHODS: We retrospectively analyzed 132 ES-SCLC patients treated with first-line CIT from January 2019 to December 2024 at Xuzhou Medical University Affiliated Hospital. Inclusion criteria included histologically confirmed ES-SCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and at least two cycles of first-line CIT. Patients were categorized into two groups: CIT plus RT (n=73) and CIT alone (non-RT) (n=59). Baseline characteristics, tumor response, and treatment-related adverse events (AEs) were compared between groups using Chi-squared tests. Progression-free survival (PFS), primary tumor PFS (PFS-PT), distant metastasis PFS (PFS-DM), and overall survival (OS) were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were used for univariate and multivariate analyses. RESULTS: Baseline characteristics were largely balanced, except for significantly higher baseline brain (28.8% vs. 8.5%, P=0.004) and adrenal metastases (20.6% vs. 5.1%, P=0.01) in the RT group. The CIT + RT group demonstrated significantly superior outcomes compared to the CIT-alone group. The objective response rate (83.6% vs. 49.2%, P<0.001) and disease control rate (90.4% vs. 62.7%, P<0.001) were higher with RT. Median OS [21.0 vs. 13.0 months; hazard ratio (HR) =0.514, 95% confidence interval (CI): 0.331-0.798] and median PFS (9.5 vs. 6.0 months; HR =0.552, 95% CI: 0.383-0.796) improved significantly with RT. RT also extended median PFS-PT (11.8 vs. 8.0 months, P<0.001) and PFS-DM (11.8 vs. 7.1 months, P=0.01). RT independently predicted better OS and PFS. Consolidation RT demonstrated greater efficacy compared to salvage RT (both P<0.01). No significant differences in AE incidence (Grade I-II or III-IV) were observed. CONCLUSIONS: This retrospective study found that adding local RT to first-line CIT significantly improved OS and primary tumor control in ES-SCLC without increasing AEs. RT may serve as an independent favorable prognostic factor, and consolidation timing appears crucial. These findings generate hypotheses requiring prospective validation.