Prophylactic Cranial Irradiation Improves Survival in Limited-Stage SCLC

Prophylactic cranial irradiation (PCI) was associated with significantly improved overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC), according to data from a nationwide, real-world analysis from the Canadian SCLC Database (CASCADE) published in JTO Clinical and Research Reports.¹

What were the efficacy findings of CASCADE?

The median OS was 29.8 months (95% CI, 26.7-34.5) in patients who received PCI vs 19.0 months (95% CI, 16.6-23.5) in those who did not (HR, 0.67; 95% CI, 0.55-0.82; log-rank P <.0001). On multivariable analysis, PCI remained independently associated with improved OS (HR, 0.70; 95% CI, 0.57-0.86; P <.001), a finding that was consistent in an inverse probability of treatment weighting analysis (HR, 0.70; 95% CI, 0.58-0.85; P = .0003). In a predefined subgroup of 217 patients who underwent baseline brain MRI staging, PCI was again associated with improved median OS (32.8 vs 19.4 months; P = .0091).

PCI was also associated with improved progression-free survival (PFS), with a median PFS of 17.5 months (95% CI, 15.5-20.6) vs 10.9 months (95% CI, 9.6-12.9) in patients who did not receive PCI (HR, 0.60; 95% CI, 0.50-0.72; P <.0001); the association persisted on multivariable analysis (HR, 0.61; 95% CI, 0.50-0.74; P <.001). In a predefined subgroup with brain-failure data, PCI significantly reduced the cumulative incidence of brain metastasis (HR, 0.41; 95% CI, 0.28-0.60; P <.001), corresponding to a 63% lower risk on multivariable analysis. Any brain metastasis was documented in 20.73% of patients who received PCI vs 38.97% of those who did not.

“With improved control of thoracic and extracranial disease through chemoradiation and adjuvant immunotherapy, the potential value of PCI in reducing central nervous system [CNS] relapse may become increasingly important," corresponding author Benjamin H. Lok, MD, associate professor of radiation oncology at the University of Toronto and a radiation oncologist at Princess Margaret Cancer Centre, wrote in the publication with study coinvestigators.¹ “Our findings suggest that PCI may continue to provide a meaningful survival benefit, including among patients who undergo baseline MRI staging. These findings support the continued role of PCI and highlight the need for further study in the modern imaging era.”

How was CASCADE designed?

CASCADE was a Canadian multi-institutional database that included patients with SCLC from 9 institutions. This retrospective, real-world analysis included patients with pathologically confirmed LS-SCLC diagnosed between 2004 and 2022, comparing outcomes between patients who received PCI and those who omitted it.

A total of 607 patients were eligible for analysis, with 388 receiving PCI and 219 not receiving it; the median age was 66.0 years (range, 40-90). Among patients treated with PCI, most received 25 Gy (91.3%). OS and PFS were assessed using Kaplan-Meier methods and Cox proportional hazards models, and brain metastasis incidence was evaluated in a predefined subgroup using competing-risk methods.

The primary end point of the study was OS, assessed from the time of pathologic SCLC diagnosis to death from any cause. Secondary end points included PFS and brain metastasis incidence.

The authors noted several limitations, including the potential for selection bias inherent to a retrospective analysis; patients selected for PCI were younger. The authors also highlighted the absence of long-term neurocognitive outcome data, one of the primary deterrents to PCI use. They also noted that much of the cohort predated the widespread adoption of immunotherapy for LS-SCLC.

These findings contrast with a randomized trial in extensive-stage SCLC (ES-SCLC), which demonstrated no survival benefit from PCI compared with observation with MRI surveillance.² The authors highlighted that the ongoing MAVERICK trial (NCT04155034) is evaluating MRI surveillance vs PCI in both LS-SCLC and ES-SCLC, and that an updated analysis of the phase 3 ADRIATIC trial (NCT03703297) supporting adjuvant durvalumab (Imfinzi) reflects an evolving treatment landscape in which the role of PCI remains uncertain.^3,4

References

1. Lone AH, Ye XY, Zhan LJ, et al. Prophylactic cranial irradiation and survival in limited-stage SCLC: a multicenter real-world analysis from the Canadian SCLC Database (CASCADE). JTO Clin Res Rep. 2026;7(8):101030. doi:10.1016/j.jtocrr.2026.101030
2. 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.
3. S1827 (MAVERICK) testing whether the use of brain scans alone instead of brain scans plus preventive brain radiation affects lifespan in patients with small cell lung cancer. ClinicalTrials.gov. Updated June 11, 2026. Accessed August 4, 2026. https://tinyurl.com/35fbw9cv
4. Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313-1327. doi:10.1056/NEJMoa2404873.