Surveillance is not observation: MAVERICK challenges routine prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC)

By Avinash Chaurasia, MD, Brooke Army Medical Center

Presenting author: Paul Brown, MD

For decades, prophylactic cranial irradiation (PCI) has occupied a familiar place in small-cell lung cancer (SCLC) care. The rationale was clear: earlier trials showed PCI could reduce brain metastases and improve survival.^1,2 But those data came from an era before routine brain MRI. In today’s practice, the central question is different: if MRI can rule out occult disease and detect new metastases early, does PCI still provide enough added value to justify its cognitive tradeoffs?

SWOG S1827/MAVERICK brings that question into the modern imaging era. The international phase III trial randomized 304 patients who had completed initial therapy for limited- or extensive-stage SCLC and had no brain metastases on MRI to structured MRI surveillance alone or surveillance plus PCI (25 Gy in 10 fractions). MRI and cognitive testing were conducted every three months during year one and every six months during year two. The primary endpoint was cognitive failure-free survival (CFFS), defined as failure on any of three standardized tests or death.

The results favor surveillance. At a median follow-up of 22 months among living patients, MRI surveillance reduced the hazard of cognitive failure or death (HR 0.60, 90% CI 0.46-0.78; p=0.001). Because death was part of the composite endpoint, the competing-risk analysis is especially relevant: MRI surveillance was also associated with a lower cumulative incidence of protocol-defined cognitive failure (subdistribution HR 0.62, 90% CI 0.48-0.79; p=0.001). The CFFS effect did not appear to differ by stage or immunotherapy use, although nonsignificant interaction tests should not be read as proof of identical benefit across subgroups.

Importantly, this was not a comparison against outdated PCI. Seventy-seven percent of patients assigned to PCI received hippocampal-avoidant treatment, and the favorable CFFS estimate for MRI surveillance persisted among patients for whom that technique was declared before randomization (HR 0.63, 90% CI 0.47-0.83; p=0.006). NRG-CC003 showed that hippocampal avoidance reduced failure on any neurocognitive test compared with conventional PCI, although it did not improve the trial’s primary delayed-recall endpoint.³ MAVERICK therefore suggests that modern PCI technique may mitigate, but does not necessarily erase, the cognitive burden of treatment.

Patient-reported outcomes add nuance rather than a simple parallel finding. At day 180, neither PROMIS nor MDASI cognitive concerns differed significantly between groups. Longitudinal modeling favored MRI surveillance on PROMIS cognitive concerns, and overall quality of life favored surveillance at 90 and 180 days, although the abstract did not report effect sizes or minimally important differences. Survival data are also not yet final. At 128 of 190 planned deaths, no adverse survival signal was evident with MRI alone (HR 0.90, 90% CI 0.67-1.20). The upper confidence bound is below the 1.25 noninferiority margin, but the prespecified final analysis remains pending.

The trial may be most practice changing in limited-stage SCLC, which represented 68% of enrollment. MRI surveillance is already an accepted option in extensive-stage disease after a Japanese randomized trial found no survival advantage from PCI when serial MRI was required.⁴ Comparable randomized omission data in limited-stage disease have been lacking. Several clinically important details are still needed, including brain-metastasis outcomes, salvage treatment, neurologic death and toxicity. Those data will matter because MRI surveillance is not passive observation; it requires access, adherence and timely salvage therapy.

For patients who can complete that pathway, MAVERICK makes a strong case that surveillance is more than a compromise. It may become the standard against which routine PCI must now justify itself.

References

1. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999;341(7):476-484. doi:10.1056/NEJM199908123410703
2. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664-672. doi:10.1056/NEJMoa071780
3. Gondi V, Pugh SL, Mehta MP, et al. Hippocampal avoidance during prophylactic cranial irradiation for patients with small cell lung cancer: Randomized phase II/III trial NRG-CC003. J Clin Oncol. 2025;43(32):3516-3525. doi:10.1200/JCO-25-00221
4. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663-671. doi:10.1016/S1470-2045(17)30230-9

Abstract LBA 03, SWOG S1827/MAVERICK: A Randomized Phase III Trial of Brain MRI Surveillance with and without Prophylactic Cranial Irradiation (PCI) for Small-Cell Lung Cancer (SCLC), was presented during the CT 01 - Clinical Trials Session, at ASTRO's 68th Annual Meeting.