The addition of radiotherapy to adjuvant chemotherapy has a combinatorial effect in pN2 non-small cell lung cancer only with extranodal invasion or multiple N2 metastasis.

Objectives The benefit of adjuvant therapy for heterogenous group of pathological N2 (pN2) non-small cell lung cancer (NSCLC) remains unclear. We evaluated the prognostic effect of adjuvant therapy after stratifying patients with pN2 according to subdivided N2 descriptors. Materials and methods We performed a retrospective analysis of clinical outcomes in patients with pN2 NSCLC who underwent upfront surgery. N2 descriptors were subdivided as single N2 metastasis without N1 involvement (pN2a1), single N2 with metastasis with N1 involvement (pN2a2), and multiple N2 metastasis (pN2b). Results From 2005-2017, 838 patients with pN2 NSCLC underwent complete resection. There were 173 (21.0 %), 338 (40.3 %), and 324 (38.7 %) in the pN2a1, pN2a2, and pN2b groups. Patients who received chemoradiotherapy (CRTx; n = 389, 46.4 %) or chemotherapy (CTx; n = 204, 24.3 %) had similar prognoses, which were better than prognoses in patients who received with radiotherapy (RTx; n = 116, 13.8 %) or those who did not receive adjuvant therapy (n = 129, 15.4 %). According to the stratified multivariable Cox analysis, patients with pN2b stage in the CTx group had a significantly poor prognosis than those in the CRTx group (hazard ratio, 1.38; 95 % confidence interval, 1.03-1.98; p = 0.046). The difference in survival outcomes between the CRTx and CTx groups was significant in patients with extranodal invasion (ENI) (p = 0.011), but not in those without ENI (p = 0.527) CONCLUSIONS: Adjuvant CTx improves the overall and recurrence-free survival in patients with pN2 NSCLC undergoing upfront surgery with complete resection. RTx with adjuvant chemotherapy has a combinatorial effect on pN2 NSCLC only with ENI or multiple N2 metastasis.