Chemoradiotherapy for NSCLC patients with a high predicted risk of irradical resection

Abstract

Purpose or Objective Irradical (R1-2) resection of non-small cell lung cancer (NSCLC) is a detrimental prognostic factor. Recently, an internationally validated risk score for pre-treatment prediction of irradical resection was developed by Rasing et al. We hypothesized that chemoradiation therapy (CRT) could serve as an alternative approach in patients with a high predicted risk of an irradical resection and aimed to compare overall survival outcomes between surgery and CRT in those patients. Materials and Methods From the original prediction model development cohort, the patients with a predicted high risk for an irradical resection (Rasing score >4) who underwent surgery for stage IIB-III NSCLC in 2015-2018 in The Netherlands were selected. Additionally, from the Netherlands Cancer Registry, patients who received CRT for stage IIB-III NSCLC in 2015-2018 were selected. The surgery and CRT patient groups were matched using 1:1 nearest-neighbor propensity score matching to correct for imbalances in baseline. The primary endpoint of overall survival (OS) was compared using Kaplan-Meier analysis. Subgroup analyses were performed using interaction terms in Cox regression models. Results A total of 2,582 patients who received CRT and 638 surgery patients were eligible. After matching, 523 well- balanced pairs with a high pre-treatment risk of irradical resection remained. In the surgery group, 409 (78.2%) had a R0 resection and 114 (21.8%) a R1-2 resection. Median OS in the surgery group was 46.3 months, compared to 26.5 months in the CRT group (HR 1.42, 95% CI 1.19-1.69, p<0.001). Surgical patients after a R1-2 resection had a worse survival compared to the total CRT group (median OS 20.3 versus 26.5 months, HR 0.73, 95% CI 0.57-0.94, p=0.016). Subgroup analysis did not yield any significant subgroup differences. Conclusion In NSCLC patients at high risk of irradical resection according to the Rasing score, CRT results in inferior survival compared to surgery. Therefore, a choice of CRT instead of surgery cannot solely be based on the Rasing risk score. Since patients who end up receiving a R1-2 resection do have detrimental outcomes compared to primary CRT, the treatment decision should be based on additional information not covered by the Rasing score, such as imaging features and the surgeon’s confidence in achieving a R0 resection.