Definitive radiotherapy provides comparable survival with lower toxicity compared with concurrent chemoradiotherapy...

Long-course induction chemoimmunotherapy (⩾3 cycles) is increasingly used to downstage unresectable non-small-cell lung cancer (NSCLC). However, the optimal definitive local treatment for patients who remain inoperable after induction-definitive radiotherapy (RT) alone versus concurrent chemoradiotherapy (CRT)-remains unclear.

To compare survival and toxicity outcomes between definitive RT and CRT following induction chemoimmunotherapy in unresectable NSCLC.

This was a single-center retrospective cohort study using stable inverse probability of treatment weighting (sIPTW) to balance baseline characteristics between treatment groups.

Consecutive patients with unresectable NSCLC without known actionable driver mutations who remained inoperable after long-course induction chemoimmunotherapy and subsequently received definitive RT or CRT were included. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and compared with weighted Cox proportional hazards models. Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events. An exploratory analysis evaluated the association between consolidation immunotherapy and PFS.

A total of 153 patients were included (RT, n = 63; CRT, n = 90). At a median follow-up of 25.8 months, the 1- and 2-year PFS rates were 83.5% and 54.3% in the RT group, compared with 82.1% and 61.1% in the CRT group (hazard ratio (HR) = 0.83; 95% confidence interval (CI), 0.51-1.37; p = 0.46). After sIPTW adjustment, PFS remained comparable (HR = 0.80; 95% CI, 0.47-1.35; p = 0.46). OS was also similar between groups. Grade 3-4 hematologic toxicity was more frequent with CRT (24.4% vs 9.5%; p < 0.001). Consolidation immunotherapy was associated with a numerical but non-significant PFS improvement (HR = 0.78; 95% CI, 0.48-1.27; p = 0.32).

In patients with unresectable NSCLC who remain inoperable after long-course induction chemoimmunotherapy, definitive RT alone provides survival outcomes comparable to CRT while reducing severe hematologic toxicity. RT alone may represent a reasonable definitive option for carefully selected patients in this setting.