Small cell lung cancer (SCLC) is associated with high rates of brain metastases relative to other solid tumors; 40% to 60% of patients with SCLC develop brain metastases without prophylactic treatment. While prophylactic cranial irradiation (PCI) has been included as a standard of care (SOC) in limited-stage SCLC (LS-SCLC) and is a guideline-recommended option for select patients with extensive-stage SCLC (ES-SCLC), concerns have been raised about cognition-related toxicity and impaired quality of life, said Chad G. Rusthoven, MD, Adjoint Associate Professor of Radiation Oncology at the University of Colorado Anschutz.
Dr. Rusthoven is the lead author of the international phase III SWOG S1827/MAVERICK trial of brain MRI surveillance with or without PCI for SCLC. He presented results from the study on Sunday, September 13, during Presidential Symposium 1 at the 2026 World Conference on Lung Cancer (WCLC) in Seoul, Republic of Korea.
Presidential Symposium 1
Brain MRI Surveillance +/- PCI for SCLC
Registered WCLC 2026 attendees can watch Dr. Chad G. Rusthoven and other presenters with on-demand access to session recordings from the Presidential Symposium 1. LEARN MORE
Discussing the trial’s rationale, Dr. Rusthoven noted that PCI became the SOC after studies in a “pre-MRI era” showed improved overall survival (OS) with PCI compared with observation.
PCI has become increasingly controversial in the era of routine brain MRI staging and surveillance, as brain MRI surveillance may lead to earlier detection of brain metastases and permit more timely and effective salvage therapy, he said.
“The MAVERICK study tested the hypothesis that, compared with PCI, MRI surveillance alone would result in superior cognitive failure-free survival (CFFS) without decline in OS,” Dr. Rusthoven said.
The phase III MAVERICK trial enrolled 304 patients with SCLC, 68% with LS-SCLC and 32% with ES-SCLC, without brain metastases at diagnosis within 28 days after completing first-line therapy. Upfront immunotherapy was used in 41%.
After a protocol amendment based on low accrual rates, the primary endpoint was changed from OS to CFFS, which was previously a key secondary endpoint.
In addition to OS, the non-inferiority design included other secondary endpoints: brain metastasis-free survival, progression-free survival (PFS), cumulative incidence of brain metastases, cognitive failure, and toxicities. Patients were stratified by disease stage (limited vs. extensive) and receipt of immunotherapy. Of the 152 patients randomized to MRI surveillance with PCI, 77% received hippocampal avoidance PCI (HA-PCI).
“MRI surveillance alone resulted in a statistically significant improvement in CFFS, with a hazard ratio of 0.60,” Dr. Rusthoven said. However, cognitive testing was only obtained in English- and French-speaking patients in this global trial, and 29 patients, despite assignment, did not receive PCI in the MRI-plus-PCI arm.
The estimated 6-month CFFS rate with MRI alone was 37.8%, compared with 16.5% with MRI and PCI. Subgroup analyses indicated no significant differences in CFFS between treatment arms by either disease stage or receipt of immunotherapy. Immunotherapy was administered in just 39% of study patients, as patients with ES-SCLC comprised 31% of the study population. Its use in patients with LS-SCLC in the study conducted between 2020 and 2025 was not reported.
Preliminary OS analysis, after 128 events, indicated no signal for a difference in OS between treatment arms. Final OS analysis is planned after 190 events.
“PCI did appear to alter the pattern of initial failure,” Dr. Rusthoven said, pointing out that patients who did not receive PCI had higher rates of CNS progression, with 18% experiencing progression first in the brain. Patients in the MRI plus PCI arm experienced more extracranial-only progression, 45% versus 31%.
“Although brain metastases-free survival numerically favored MRI plus PCI, the differences between the arms were not statistically significant,” he said.
Additionally, there was no statistically significant difference in overall PFS between the arms.
Treatment-related adverse events (TRAEs) were significantly higher in patients who received PCI in addition to MRI surveillance than in those in the MRI-alone arm; grade 2 or higher TRAEs were reported in 41.3% versus 7.1%, and grade 3 or higher TRAEs in 7.9% versus 0.8%.
“Overall, these results support MRI surveillance alone as the preferred management approach in patients with SCLC,” Dr. Rusthoven concluded.
The meaningful improvement in CFFS, reduction in toxicity, and the absence of a difference in PFS suggest that “on balance, some [clinicians] may omit PCI for patients,” he said, while also acknowledging the questions about access to MRI surveillance and the importance of the final OS readout raised by study discussant Hideyuki Harada, MD, PhD.
Dr. Harada, Chief of the Division of Radiation Therapy at Shizuoka Cancer Center, contextualized the MAVERICK study, pointing out that data supporting adoption of PCI in SCLC were generated in the late 1990s before MRI availability. Dr. Harada noted that in the MRI-alone arm of MAVERICK, the brain was the site of first progression in 18% of patients. These patients would benefit from cranial irradiation, regardless of whether it is prophylactic or therapeutic, he said.
“If an MRI surveillance strategy cannot be adopted, no PCI and no MRI surveillance would be harmful in these patients. If MRI surveillance could not be adopted, PCI should be considered for the patient,” Dr. Harada said. “When MRI surveillance becomes the SOC, the accessibility [of MRI] becomes an important issue.”
In addition to the final OS results, we await more detailed analyses of cognitive function, quality of life, and immunotherapy use, expected from MAVERICK. Coupled with findings from the ongoing PRIMALUNG trial, this may help clarify the role of MRI surveillance alone in SCLC care.
