Efficacy of perioperative chemotherapy for pulmonary high-grade neuroendocrine carcinomas: a propensity score matching analysis

Hiroyuki Ogawa, Yugo Tanaka, Yoshitaka Kitamura, Nahoko Shimizu, Takefumi Doi, Daisuke Hokka, Shinya Tane, Wataru Nishio, Masahiro Yoshimura, Yoshimasa Maniwa


Background: Large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are categorized as high-grade neuroendocrine carcinoma (HGNEC). We analyzed the efficacy of perioperative chemotherapy for HGNEC and the prognostic factors.
Methods: We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNEC between January 2001 and December 2014. The overall survival (OS) was estimated by the Kaplan-Meier method. Propensity score matching was performed to compare the OS between the treatment groups. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC.
Results: We analyzed 146 HGNEC patients (LCNEC n=92, SCLC n=54) without synchronous multiple cancers, who underwent complete resection. Seventy patients (LCNEC n=31, SCLC n=32) received perioperative chemotherapy and all of them received a platinum-based anticancer drug. Perioperative chemotherapy significantly improved the 5-year OS rates of HGNEC patients (all stages: 74.5% vs. 34.7%, P<0.01, stage I: 88.5% vs. 40.0%, P<0.01). The efficacy of perioperative chemotherapy was similar between LCNEC and SCLC patients [LCNEC all stages: hazard ratio (HR) 0.27, P<0.01, LCNEC stage I: HR 0.27, P=0.01; SCLC all stages: HR 0.38, P=0.02, SCLC stage I: HR 0.34, P=0.06]. The survival benefit of perioperative chemotherapy for HGNEC patients was confirmed by propensity score matching analysis (HR 0.31, P<0.01). The multivariate analysis revealed that perioperative chemotherapy (HR 0.29, P<0.01), sublobar resection (HR 2.11, P=0.04), and lymph node metastasis (HR 3.34, P<0.01) were independently associated with survival.
Conclusions: Surgical resection combined with perioperative chemotherapy was considered to be effective even for stage I HGNEC patients. Sublobar resection might increase the risk of death in HGNEC patients.