How do you incorporate PCI into your management of patients with extensive stage SCLC?

I must admit, that I was never a fan of PCI in the extensive SCLC setting. With the publication of the Japanese study, I am definitely not strongly recommending PCI. I think it is good to see the patient so that we can discuss both PCI and thoracic consolidation, but I have been doing more thoracic consolidation than PCI lately. An exception might be the patient in whom it was debatable as to whether they had limited vs extensive disease. I saw such a case recently, where the patient was treated as extensive disease due to the possibility of two small lung metastases. In retrospect, I think these are GGOs since they didn't change with chemotherapy. Or another patient had a pleural effusion but it was never tapped, so could be just transudate. In these situations, I discuss PCI in a more positive way. 

For patients with extensive-stage (ES) SCLC, I would offer MRI surveillance without prophylactic cranial irradiation (PCI).

The foundational evidence for PCI in ES-SCLC comes from the EORTC Phase 3 trial (Slotman et al., PMID 17699816), which randomized ES-SCLC patients who had responded to upfront chemotherapy to PCI vs observation (i.e., imaging for neurological symptoms) and reported improved overall survival (OS) with PCI.

However, concerns remain regarding the potential adverse effects of PCI on cognition and quality of life (QOL), and PCI has become increasingly controversial in the modern era of brain MRI surveillance. The NCCN SCLC guidelines recommend brain MRI surveillance for patients with both limited-stage (LS) and ES-SCLC who have completed upfront therapy, regardless of PCI delivery. MRI surveillance may allow for earlier detection of brain metastases and more effective salvage therapy, potentially eliminating the OS advantage previously observed with PCI.

To test this hypothesis in patients with ES-SCLC, a phase 3 trial conducted in Japan randomized ES-SCLC patients to MRI surveillance with or without PCI. Although brain metastases were reduced with PCI, no significant differences were observed in OS or PFS between the study arms (Takahashi et al., PMID 28343976).

More recently, we presented the SWOG S1827/MAVERICK trial at the 2026 WCLC and ASTRO meetings. MAVERICK enrolled patients with either LS or ES-SCLC who had responded to upfront therapy and had no evidence of brain metastases on MRI. Patients were randomized to MRI surveillance ± PCI. The randomization was stratified by disease stage (LS/ES), receipt of immunotherapy, and performance status. Hippocampal avoidance (HA)-PCI was allowed at MD discretion (77% of PCI delivered was HA-PCI). MRIs were performed every 3 months during year-1 and every 6 months during year-2. The initial primary endpoint was OS with a non-inferiority design requiring over 600 patients, but due to accrual, the protocol was amended to make cognitive failure-free survival (CFFS) the primary endpoint with a target accrual of 300 patients (previously CFFS was the key secondary endpoint). CFFS was defined as time to cognitive decline or death. Neurocognitive function was assessed using a standardized, validated testing battery (HVLT-R, COWA, TMT A&B) performed on the same schedule as MRIs and scored by a blinded central reviewer. MAVERICK completed accrual in December 2025 with a total of 304 patients enrolled. Patient characteristics were well balanced between the arms. Overall, 68% had LS and 32% had ES-SCLC. At a median follow-up of 22 months for living patients, we observed the following:

• MRI alone was associated with an improvement in the primary endpoint of cognitive failure-free survival (CFFS) (HR 0.60, 90% CI 0.46-0.78, p=0.0005). Thus, patients randomized to MRI alone were significantly more likely to be alive and free from cognitive decline compared to those randomized to MRI+PCI.
• There were no significant differences in the CFFS benefit of MRI alone by either stage (LS-SCLC, HR with MRI alone = 0.59; ES-SCLC, HR with MRI alone = 0.65; interaction p-value = 0.79) or receipt of immunotherapy.
• Subgroup analyses limited to patients receiving HA-PCI showed nearly identical results (HR with MRI alone = 0.61, 90% CI 0.45-0.82, p=0.003).
• Preliminary analyses of OS after 128 events suggest no differences in survival (HR with MRI alone 0.90, 90% CI 0.67-1.20). Final analysis of OS will be reported after 190 events.
• PCI reduced the cumulative incidence of brain metastases (12-month estimate: 30% with MRI alone vs 15% with MRI+PCI; sHR 2.19, 95% CI 1.31-3.64).
• However, there were no significant differences in progression-free survival (PFS) (HR with MRI alone 0.96, 90% CI 0.75-1.23).
• PCI altered the patterns of initial disease failure (brain or brain + extracranial failure: 18% [MRI] vs 5% [MRI+PCI]; extracranial only: 31% [MRI] vs 45% [MRI+PCI]).
• Patient-reported outcomes favored MRI alone overall: better PROMIS cognitive function, better LASA overall QOL at 90 days, no differences in MDASI cognitive factor.
• PCI was associated with increased treatment-related toxicity (grade 2+: 41% vs 2%; grade 3+: 8% vs 1%, p=0.004).

In the setting of routine brain MRI surveillance, currently there is no signal of either a PFS or OS benefit with PCI in patients with ES-SCLC from two phase 3 randomized trials (the Japanese trial and MAVERICK). Conversely, MRI surveillance alone appears to be associated with meaningful clinical benefits to patients, including superior cognitive failure-free survival, better QOL, and less toxicity.

Note that the EORTC-1901/PRIMALung trial, which has a similar design to MAVERICK, remains ongoing.

We individualize based on the extent of response and the extent of extrathoracic disease at presentation and after chemotherapy. The fact that no other intervention in the last 20 yrs has changed survival for extensive stage SCLC except for the EORTC study, despite it's design flaws (survival doubled with PCI), makes us treat more often than not. That being said, somebody with persistent multiple visceral metastatic disease in the liver is one in whom we are less likely to offer PCI.

The recent interim analysis results of the S1827 MAVERICK trial presented by Dr. @Dr. First Last at WCLC 2026 show that MRI surveillance is a good option for SCLC patients vs PCI, with an HR of 0.6 (90% CI 0.46-0.78, p=0.0005) for the primary endpoint of cognitive failure-free survival. I think for LS-SCLC, I would wait for the final analysis and also the EORTC trial, but for ES-SCLC, I consider this a nail in the coffin for the use of PCI.

I would avoid giving PCI in the management of extensive-stage SCLC. The SWOG MAVERICK trial reinforces the use of surveillance MRI with close follow-up rather than PCI. We need to wait for the trial results to mature with longer follow-up to see the overall survival outcomes for both arms.

I offer in cases of CR to chemo.

So the cost and anxiety of multiple MRI scans outweigh the cost of PCI with hippocampus avoidance?