Assessing the Impact of Ablation Plus Immunotherapy in Advanced NSCLC: Insights from the BOOSTER Phase 2 Trial

In the BOOSTER trial, adding local tumor ablation to ongoing anti-PD-1/L1 therapy markedly extended progression-free survival in advanced NSCLC with oligo-residual disease.

The randomized phase 2 trial demonstrates an immediately actionable approach to prolong disease control when oligoprogression or oligo-residual disease appears after initial immunotherapy.

Previously, continuing anti-PD-1/L1 alone was a common strategy for oligo-residual disease, but observation frequently yielded limited durable control. Combining focal ablation with ongoing systemic therapy targets resistant clones in discrete sites and fills a practical gap in current management.

The BOOSTER trial enrolled patients with advanced NSCLC who had oligo-residual disease after initial anti-PD-1/L1 therapy and compared continued immunotherapy alone versus immunotherapy plus local tumor ablation, with progression-free survival as the primary endpoint. The core efficacy result was definitive: median PFS was 26.7 months with ablation plus immunotherapy versus 11.7 months with immunotherapy alone (p<0.001, HR=0.213). The magnitude of benefit—more than doubling median PFS—signals a clinically meaningful extension of disease control with the combined approach.

Cryoablation produced a secondary signal of potentially greater benefit compared with thermal ablation, a difference that correlated with higher post-procedure interferon-alpha levels in the trial. The association with elevated IFN-α is biologically plausible as a mediator of systemic immune activation, but it remains an explanatory signal rather than definitive proof; modality choice can reasonably favor cryoablation where anatomy, expertise, and resources permit while awaiting confirmatory data.

The combination was generally well tolerated, with no unexpected high-grade toxicities and rare severe ablation-related events in the reported cohort. Operationally, it's important to view local ablation as complementary to ongoing systemic therapy for patients with limited residual disease burden: pause immunotherapy per local peri-procedural protocols and resume once post-ablation inflammatory changes stabilize, coordinate care through multidisciplinary planning, and prioritize patients with limited lesions and good performance status for combined-treatment pathways.