Neoadjuvant Treatment Followed by Surgery Versus Chemoradiation in Stage IIIA-N2 Non–small Cell Lung Cancer on Behalf of GOECP/SEOR-GICOR

Abstract

Purpose/Objective(s) A subset analyses of randomized intergroup trial (INT0139) published in 2009, suggested that surgery after neoadjuvant treatment in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) may increase the survival. Due to the difficulty in recruiting this subset of patients in clinical trials, we have designed a retrospective multicenter observational study to compare neoadjuvant treatment based on chemoradiation or chemotherapy followed by surgery (CRTS) with definitive chemoradiation (CRT).

Materials/Methods 297 NSCLC patients with stage T1-T3N2M0 underwent CRTS or CRT between January 2005 and December 2014, in 15 hospitals in Spain. In both arms, chemotherapy was platinum-based. Minimum radiation dose was 45 Gy in the CRTS group and 60 Gy in the CRT group. It was delivered in daily fractions of 1.8-2 Gy/day, with 3D conformal radiotherapy (N=237), intensity modulated radiation therapy (N=3) or volumetric modulated arc therapy (N=5). Patient and tumor characteristics were balanced by propensity score analysis method. The primary endpoint was overall survival (OS).

Results 117 patients (median age 62 years, range 41-78) were treated with CRTS and 180 patients (65 years, range 37-82) with definitive CRT. Comparing CRTS with CRT patients, performance status was 0-1 in 99.1% vs. 97.2%; 60.6% vs. 64.4% were T1 or T2 tumors, (p=0.014); 38.4% vs. 57.2% presented two or more positive nodal stations (p=0.005); and 6.8% vs. 14.4% showed a positive nodal size ≥ 3 cm (p=0.044). Histopathological confirmation of mediastinal lymph nodes was performed in 58.1% and 65% patients, respectively. In CRTS group, 52.13% patients were treated with neoadjuvant CRT and 82.0% underwent lobectomy.

Median follow-up was 27 months (43 months in CRTS and 23 months in CRT). Median OS was 58 months in CRTS vs. 27 months in CRT (hazard ratio [HR] 0.36, 95% CI: 0.23-0.56; p<0.001) after propensity score adjustment. Lobectomy vs. neumonectomy, (111 vs. 35 months, p=0.004), pT0-T2 status vs. pT3-T4 (111 vs. 22 months, p<0.001), doses ≥60 Gy vs. <60 Gy (25 vs. 14 months, p=0.001) and no treatment interruptions or interruptions ≤1 week vs. >1 week, (37 vs. 30 months, p=0.03), were associated with higher OS in a regression analisys. Progression-free survival (PFS) was better in CRTS than CRT group, median 57 months vs. 14 months, HR 0.35, (95% CI 0.22-0.54; p<0.001). Although grade > 3 oesophagitis and pneumonitis were similar in both arms, grade >3 hematological toxicity was greater in CRT group (2.9% vs. 21.1%, p=0.001). Adjusted treatment-related mortality was 6.1% (2/77) in CRTS group vs. 7% (4/77) in CRT, (p=0.846).

Conclusion Neoadjuvant chemoradiation treatment followed by surgery in stage IIIA-N2 NSCLC patients showed a better PFS and OS compared with definitive CRT patients. Furthermore, treatment-related mortality was similar in both treatment arms.