Long-Term Survival Effect of the Interval between Postoperative Chemotherapy and Radiotherapy in Patients with Completely Resected Pathological N2 Non-Small-Cell Lung Cancer

SIMPLE SUMMARY: In patients with completely resected stage III pN2 non-small cell lung cancer (NSCLC), adjuvant chemotherapy of 4–6 cycles was recommended prior to post-operative radiotherapy (PORT). However, some were given concurrently or early-sequentially with PORT. The objectives of this study were to verify the benefit of adjuvant sequential chemotherapy and radiotherapy (SCRT) relative to that of concurrent chemoradiotherapy (CCRT) in an Asian population and to identify the optimal timing of initiation of PORT as part of adjuvant SCRT. A longer interval (>104 days and <180 days) between the initiation of adjuvant chemotherapy and PORT was associated with improved OS compared with CCRT. No locoregional recurrence-free survival (LRFS) difference related to the interval between the initiation of adjuvant chemotherapy and PORT was observed. In older patients (aged >60 years), the benefit of delayed PORT initiation was more significant. We suggest that PORT should be postponed in the completed-resected pN2 elderly patients. ABSTRACT: (1) Purpose: To investigate the effects of the time interval between initiation of adjuvant chemotherapy and radiotherapy on survival outcomes in patients with completely resected stage IIIA pN2 non-small-cell lung cancer (NSCLC); (2) Methods: Data on 2515 patients with completely resected stage IIIA pN2 NSCLC in 2007–2017 were extracted from the Taiwan Cancer Registry Database. The survival outcomes in patients who underwent concurrent chemoradiotherapy (CCRT) and sequential chemotherapy and radiotherapy (SCRT) with either a short (SCRT1) or long (SCRT2) interval between treatments were estimated using Kaplan–Meier, Cox regression, and propensity score matching (PSM); (3) Results: Multivariate analyses of OS showed that SCRT2 (hazard ratio [HR] 0.64, p = 0.017) was associated with improved overall survival (OS). After PSM, the median OS periods were 64 and 75 months in the SCRT1 and SCRT2 groups, respectively, which differed significantly from that of 58 months in the CCRT group (p = 0.003). In elderly patients, SCRT2 significantly improved survival relative to CCRT before PSM (p = 0.024) and after PSM (p = 0.002); (4) Conclusions: A longer interval between initiation of adjuvant chemotherapy and postoperative radiotherapy (PORT; SCRT2) improved OS relative to CCRT; the benefits were greater in elderly patients (age >60 years).