Clinical and economic impact of recurrence in unresected non-small cell lung cancer treated with primary stereotactic body radiotherapy: A real-world study using SEER-Medicare data.

Background: Stereotactic body radiotherapy (SBRT) is the recommended treatment for inoperable, early-stage non-small cell lung cancer (NSCLC). Although prior research has assessed overall survival (OS) and recurrence rates post-SBRT, limited data exist on the clinical and economic impact of recurrence and the association between event-free survival (EFS) and OS in this patient population.

Objective: To compare OS, health care resource utilization (HRU), and costs between patients with early-stage NSCLC receiving primary SBRT, with and without recurrence, and assess the association between real-world EFS (rwEFS) and OS.

Methods: The SEER-Medicare database (2007-2020) was used to identify patients with stage I-IIB (N0) NSCLC receiving primary SBRT. Patients were categorized into recurrence and nonrecurrence cohorts based on disease recurrence status post-SBRT. OS, all-cause and NSCLC-related HRU, and health care costs were compared between patients with and without recurrence. The correlation between OS and rwEFS was assessed using the normal scores rank correlation and landmark analyses.

Results: A total of 3,014 patients met the inclusion criteria, with 1,455 (48.3%) experiencing disease recurrence. Median OS was significantly shorter for the recurrence cohort (18.9 months) compared with the nonrecurrence cohort (51.4 months; log-rank P < 0.001). Patients with recurrence had a 2.16-fold higher risk of death (95% CI = 1.94-2.42; P < 0.001). HRU and health care costs were significantly higher in the recurrence cohort, with adjusted monthly all-cause and NSCLC-related costs per patient exceeding those of nonrecurrence patients by $5,458 and $3,838, respectively (both P < 0.001). A significant correlation was observed between rwEFS and OS (ρ = 0.74; P < 0.0001).

Conclusions: Recurrence after SBRT in unresected, early-stage NSCLC was associated with worse survival and substantial economic burden. The strong correlation between rwEFS and OS suggests that EFS may serve as a good predictor for OS and be a clinically relevant trial endpoint. These findings highlight the need for novel strategies to prevent/delay recurrence.