Role of radiation therapy in the management of stage III non-small cell lung cancers: current status and controversies

Abstract

Abstract The treatment of stage III non-small cell lung cancer (NSCLC) consisting of the heterogeneous stage subsets remains a challenge. Overall, it has been gradually recognized that radiation therapy (RT) plays a crucial role in the management of stage III NSCLC. One superior sulcus tumors are the subset for which the trimodality treatments are clearly preferred. One subset of stage III NSCLC has a minimal disease burden with microscopic pN2 disease or with discrete pN2 involvement identified preoperatively, thus technically could undergo a surgical resection. For the incidentally found pN2 disease after complete surgery (IIIA-1, IIIA-2), the value of postoperative radiotherapy (PORT) has been recognized by a reassessment based on new data. However, doubt persists regarding how to define the clinical target volume for PORT. For the discrete pN2 involvement identified preoperatively (a selected part of IIIA-3), induction chemoradiation therapy (CRT) before surgery may yield a survival advantage, although the phase III randomized trials in this issue are not conclusive. The other major subset of stage III NSCLC is the infiltrative stage III NSCLC with N2 or N3 nodal disease (IIIA-3, IIIA-4, and IIIB), for which concurrent CRT is considered as the current standard of care. The potential role of radiation dose escalation/acceleration has been proposed; however, the optimal dose fractionation remains an important unresolved question. Additionally, the role of prophylactic cranial irradiation for stage III patients with high risk of brain metastasis is worth of further assessment. Moreover, how to integrate molecular targeted therapy with RT, as well as whether they had a role in stage III diseases, are other controversies actively under study in ongoing trials. This review specifically describes the updated role of RT in multimodal approach to treat stage III NSCLC and the controversies regarding these results in various situations.