Neoadjuvant therapy for resectable non-small cell lung cancer with mediastinal lymph node involvement

The optimal treatment for stage IIIA (N2) NSCLC remains controversial. Numerous studies with induction chemotherapy or chemoradiotherapy show that both approaches in the neoadjuvant setting are feasible. Outcomes following induction therapy have been associated with mediastinal nodal response, with residual mediastinal involvement a negative predictor of survival. Appropriate selection of patients to undergo resection following induction therapy is critical. Lobectomy may be safely performed following induction therapy while pneumonectomy may carry a high and possibly unacceptable rate of perioperative mortality. Combined modality therapy has increased the overall survival of patients with stage III NSCLC. Future trials looking at different induction regimens with or without radiotherapy and with or without surgery may help identify the ideal treatment for this heterogeneous disease stage. The SAKK-16/00 study is an ongoing phase III European trial randomizing patients with stage IIIA NSCLC to receive neoadjuvant chemotherapy with three cycles of docetaxel and cisplatin followed by radiation and then surgical resection, or to chemotherapy with the same regimen followed by surgery alone. Other ongoing trials include investigations of novel chemotherapeutic combinations, such as cisplatin with pemetrexed, in the phase II setting. The RTOG 0229 phase II study is evaluating neoadjuvant paclitaxel and carboplatin concurrently with radiation therapy, followed by surgery and consolidation chemotherapy with paclitaxel and carboplatin for stage III NSCLC. The combination of neoadjuvant docetaxel, carboplatin, and radiation therapy followed by surgical resection for stage III NSCLC is also currently being investigated in a phase II trial. The future of treatment for stage III NSCLC may lie in the outcome of trials investigating molecularly targeted agents, such as EGFR inhibitors, anti-angiogenic agents, or multitargeted agents. Optimal incorporation into the multimodality approach required of locally advanced N2 NSCLC will require careful investigation. The results from these trials are eagerly awaited.