Adjuvant treatment following irradical resection of stage I-III NSCLC: a population-based study

Abstract

Purpose or Objective Irradical (R1-2) resection for non-small cell lung cancer (NSCLC) is associated with a dismal prognosis. Adjuvant treatment attempts to improve survival outcomes, but evidence on the optimal strategy is limited. The purpose of this study was to compare overall survival (OS) between different adjuvant treatment strategies in these patients. Materials and Methods Out of 8,528 patients with newly diagnosed NSCLC from 2015-2018, those with an R1-2 resection were identified from the Netherlands Cancer Registry. First, OS was compared between adjuvant treatment groups ‘no therapy’, ‘radiotherapy (RT) only’, ‘chemotherapy only’, and ‘chemo- and radiotherapy (CRT)’ using multinomial propensity score-weighted Cox regression analysis. Second, three 1:1 propensity score-matched sets were created for chemotherapy versus no chemotherapy, RT only versus no therapy, and CRT versus chemotherapy only. Kaplan-Meier and Cox regression analyses for OS were performed in each set. Finally, interaction analyses were performed in abovementioned cohorts by entering interactions of patient- and tumor-related characteristics with the treatment group into Cox regression models, in order to explore whether in specific subgroups a certain treatment would have a differential effect on OS. Results A total of 427 patients were selected with a median follow-up of 23 months. In the weighted regression analysis, compared to no adjuvant therapy, chemotherapy and CRT were associated with improved OS (HR 0.41, 95%CI: 0.22-0.76; and HR 0.55, 95%CI: 0.37-0.81, respectively), whereas RT was not (HR 1.04, 95%CI: 0.73-1.50; Table 1). In the matched sets, OS was improved after chemotherapy (+/- RT) compared to no chemotherapy (HR 0.47, 95%CI: 0.32-0.69; Figure 1A). No OS difference was observed between matched groups of RT only versus no adjuvant therapy (HR 1.13, 95%CI: 0.74-1.72), nor for CRT versus chemotherapy only (HR 1.37, 95%CI: 0.70-2.71) (Figure 1B-C). Subgroup analyses showed a survival advantage for chemotherapy in patients with lymph node metastases, especially in pN2 compared to pN0 patients and a different OS for radiotherapy only compared to no therapy in poor versus good/moderate differentiation grade. Conclusion Adjuvant chemotherapy, but not radiotherapy, improves survival after an R1-2 resection in stage I-III NSCLC.