Prophylactic cranial irradiation versus active MRI surveillance for limited-stage small-cell lung cancer achieving response after chemoradiotherapy: a protocol for a randomized, controlled, multicenter, phase III trial

Abstract Background Prophylactic cranial irradiation (PCI) is the standard preventive strategy for limited-stage small-cell lung cancer (LS-SCLC). However, the evidence supporting this strategy is largely based on the pre-MRI era. With the advancement of modern MRI and treatment techniques, the survival benefit of PCI remains unclear, particularly given the potential for neurocognitive toxicity to impair quality of life. This study aims to re-evaluate the value of PCI in contemporary LS-SCLC patients and investigate whether active MRI surveillance is non-inferior to PCI regarding overall survival (OS). Methods This is a prospective, randomized, multicenter, phase III trial, enrolling patients with LS-SCLC who achieve complete response (CR) or partial response (PR) after platinum-based chemoradiotherapy. Participants will be randomly assigned (1:1) to receive either PCI or active MRI surveillance. The primary endpoint is OS. Secondary endpoints include 1- and 3-year OS rates, progression-free survival (PFS), brain metastasis rate, and neurocognitive function. Exploratory analyses will integrate clinical characteristics with the longitudinal kinetics of tumor biomarkers in collected peripheral blood to identify patient subgroups who are more likely to benefit from PCI. Discussion This study will re-evaluate the role of PCI in the MRI era for LS-SCLC. If active MRI surveillance proves non-inferior, it may provide evidence supporting a less intensive management approach that could potentially reduce treatment-related neurotoxicity and preserve quality of life. Furthermore, our trial aims to identify patient subgroups that derive a clinical benefit from PCI, and leverage serial biomarker dynamics to guide personalized clinical management for LS-SCLC patients. Trial registration This trial is registered at ClinicalTrials.gov (NCT04829708).