Neoadjuvant Chemoradiation Shows No Survival Advantage to Chemotherapy Alone in Stage IIIA Patients

Background: For operable patients with clinical stage IIIA non-small cell lung cancer, the optimum neoadjuvant treatment strategy remains unclear. Our aim was to compare perioperative and long-term outcomes for patients receiving neoadjuvant chemoradiotherapy (NCRT) versus neoadjuvant chemotherapy (NCT) alone.

Methods: We queried the National Cancer Database to identify all patients with N2 and either T1-T2 non-small cell lung cancer who received either NCRT or NCT followed by lobectomy between 2006 and 2012. Patients with T3 tumors were excluded. A propensity match analysis was performed incorporating preoperative variables, and the incidence of postoperative complications, pathologic downstaging, and long-term survival were compared.

Results: In all, 1,936 patients met criteria, 745 NCT and 1,191 NCRT. The NCRT patients were younger, less likely to be treated at an academic medical center, and more likely to have adenocarcinoma. After propensity matching, patients in the NCT group showed lower 30-day mortality (1.3% versus 2.9%) and 90-day mortality (2.9% versus 6.0%), and were more likely to undergo a minimally invasive resection (25.7% versus 14.1%). The NCRT patients were more likely to have a pathologic complete response (14.2% versus 4.0%) and to be N0 at the time of resection (45.2% versus 38.7%). In the multivariable analysis, NCRT patients were at a greater risk of mortality than NCT patients (hazard ratio 1.18, 95% confidence interval: 1.03 to 1.36).

Conclusions: In our cohort, combined neoadjuvant chemotherapy and radiation therapy was associated with improved pathologic downstaging but showed increased perioperative mortality with no improvement in long-term overall survival. For stage IIIA patients with smaller tumors without local invasion, chemotherapy alone may be the preferred neoadjuvant treatment.