Skipping prophylactic cranial radiotherapy cuts the risk for cognitive failure or death in patients with small-cell lung cancer (SCLC) who are receiving brain MRI surveillance, according to results from the MAVERICK phase 3 clinical trial.

The study, of over 300 patients with limited-stage or extensive-stage SCLC, found that MRI surveillance alone reduced the risk for cognitive failure or death by 40% vs MRI surveillance plus prophylactic cranial irradiation (PCI).

Patients who skipped radiotherapy also saw large reductions in related toxicities such as fatigue, alopecia, nausea, and poor appetite, Chad Rusthoven, MD, of the University of Colorado Anschutz School of Medicine, Aurora, reported at the World Conference on Lung Cancer (WCLC) 2026 in Seoul, Korea.

"Overall, these results support MRI surveillance as the preferred management approach for patients with small-cell lung cancer," Rusthoven said during his presentation.

Brain metastases are common in people with lung cancer. After studies showed that PCI improved overall survival (OS) in these patients, the treatment quickly became standard of care. 

But the advent of routine brain MRI staging and surveillance has made PCI increasingly controversial, Rusthoven said. A Japanese phase 3 trial found PCI had no effect on OS in patients with extensive-stage SCLC who received MRI surveillance. 

However, there are no randomized data for patients with limited-stage disease, Rusthoven noted, and PCI remains the guideline-recommended standard of care in that setting. 

MAVERICK included 304 patients with SCLC, 68% of whom had limited-stage disease, recruited between 2020 and 2025 at 139 institutions across the globe. All had completed initial therapy and had no brain metastases prior to enrolment. 

Patients were randomly assigned to MRI surveillance alone or MRI surveillance plus PCI (25 Gy in 10 fractions; 77% hippocampal-avoidant). Brain MRI was performed every 3 months during the first year and every 6 months during the second. Cognitive testing (with the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association, and Trail Making Test) was done at the same intervals. 

The trial's primary endpoint was meant to be OS , but the researchers amended the protocol after they were unable to recruit enough patients. The new primary endpoint was cognitive failure-free survival (originally a key secondary endpoint), with events defined as either cognitive failure or death. Cognitive failure was defined as a decline on one or more tests, per the reliable change index.

During a median follow-up for living patients of 22 months, skipping PCI significantly improved cognitive failure-free survival (hazard ratio [HR], 0.60; P = .0005). At 12 months, cognitive failure-free survival was 17% with MRI alone and 6% with MRI plus PCI. 

The benefits of skipping radiotherapy were similar in patients with extensive- and limited-stage disease, regardless of whether immunotherapy was given.

Preliminary analysis of OS , at 128 deaths, suggested no difference between the treatment groups (HR, 0.90; 90% CI, 0.67-1.20). The final analysis will be done after 190 events.

Patients who received PCI were less likely to have developed brain metastases at 12 months (15% vs 30%). But there was no significant difference between the groups in progression-free survival, at a median of 9.2 months in the MRI-only arm and 10.2 months in the PCI arm (HR, 0.96; 90% CI, 0.75-1.23).

In contrast, there were substantial differences in treatment-related toxicity. 

Treatment-related grade 3 or worse adverse events occurred in 0.8% of patients in the MRI-only arm vs 7.9% of those who received PCI (P = .004), including one death from encephalopathy. For grade 2 or higher events, the numbers were 1.7% and 41.3%, respectively. The most common side effects were fatigue, alopecia, nausea, and poor appetite.

Based on these and previous findings, MRI surveillance "can be considered the standard of care" for patients with extensive-stage SCLC, according to study discussant Hideyuki Harada, MD, PhD, of Shizuoka Cancer Center in Nagaizumi, Japan.

However, he said that additional data are needed to establish the best strategy for patients with limited-stage disease, which is potentially curable. That includes the final OS data from MAVERICK and the results of the PRIMALung trial, which is still enrolling.

"Until then, in my opinion, MRI surveillance remains a valid treatment option in limited-stage small-cell lung cancer," Harada said.

He also noted that MRI machines are not widely available in all countries, and when surveillance is not feasible, PCI should be considered.

Rusthoven acknowledged that "there is room for different interpretations between clinicians and guideline panels." But he emphasized that the MAVERICK trial "didn't simply show equivalence, it actually showed meaningful clinical benefits to patients in terms of cognitive failure-free survival and reduced toxicity."

"Some will look at this and feel more comfortable omitting PCI even in limited-stage disease," Rusthoven said. "But I also think Dr Harada's interpretation is quite reasonable, encouraging waiting for the overall survival analysis to be mature."

The trial was funded by the National Institutes of Health. Rusthoven reported receiving honoraria from Suzhou Liangyihui Network Technology Co Ltd, a company that provides digital platforms for oncologists and patients.