Prophylactic Cranial Irradiation and Survival in Limited-Stage SCLC: A Multicenter Real-World Analysis From the Canadian SCLC Database (CASCADE)

Introduction: Prophylactic cranial irradiation (PCI) is frequently used in limited-stage SCLC (LS-SCLC) to reduce the risk of brain failure after a response to chemoradiation. However, its benefit remains debated in the modern era, with improved imaging and surveillance techniques and evolving systemic therapy options. We conducted a nationwide real-world study using the CASCADE database to evaluate the impact of PCI on survival outcomes in patients with LS-SCLC. Methods: We analyzed patients from CASCADE, a Canadian multi-institutional database that includes patients with SCLC from nine institutions. Eligible patients with pathologically confirmed LS-SCLC diagnosed between 2004 and 2022 were included. We compared outcomes between patients receiving PCI and those omitting this treatment. Overall survival and progression-free survival were assessed using Kaplan-Meier methods and Cox proportional hazards models. Brain metastasis incidence was evaluated in a predefined subgroup of patients with data on brain failure outcomes using competing-risk methods, and a predefined subgroup analysis was conducted in patients with baseline brain magnetic resonance imaging. With multivariable analysis, PCI remained independently associated with improved overall survival (hazard ratio = 0.70, 95% confidence interval: 0.57-0.86) and progression-free survival (hazard ratio = 0.61, 95% confidence interval: 0.50-0.74). Patients treated with PCI had a reduced incidence of brain metastasis. Notably, this improvement in survival was observed in patients who received baseline brain magnetic resonance imaging. Conclusions: In this large, multi-institutional, real-world cohort, PCI for the treatment of LS-SCLC was associated with improved overall survival, likely driven in part by a reduced brain metastasis risk. These findings support the continued role of PCI and highlight the need for further study in the modern imaging era.