“Combined” small cell and “pure” small cell lung cancer: is there a clinical difference?

Abstract

To the Editor, According to the current World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) classification, small cell lung cancer (SCLC) combined with the additional component of nonSCLC is defined as ‘‘combined’’ SCLC [1]. The incidence of combined SCLC is reportedly to be low (\5 %), while a high percentage (28 %) was reported in the examination of 100 surgically resected SCLC [2]. Thus, the actual incidence of combined SCLC is still unclear. There are mixed data on survival; however, a relatively recent study suggested that the prognosis is not significantly different and that surgery might play an important role in the combined subtype [3, 4]. We retrospectively reviewed 95 consecutive patients diagnosed with SCLC at Kyoto University Hospital between January 2007 and December 2012. There were 89 ‘‘pure’’ SCLC and 6 ‘‘combined’’ SCLC (incidence rate: 6.3 %). The combined histologies were squamous cell carcinoma (n = 2), adenocarcinoma (n = 1), large cell neuroendocrine carcinoma (n = 1), squamous cell ? adenocarcinoma (n = 1), and adeno ? large cell neuroendocrine carcinoma (n = 1). Patient characteristics of both groups are listed in Table 1. Limited disease (LD) was significantly frequent and the proportion of patients with a normal range of neuron-specific enolase (NSE) or progastrin-releasing peptide (ProGRP) at diagnosis was significantly high in the combined subtype. Median overall survival (OS) of the pure subtype was 16.3 months and that of the combined subtype was 12.1 months (p = 0.24). Because five out of the six patients with the combined subtype had LD, survival analysis including only LD patients was performed (Fig. 1). Patients with the combined subtype underwent surgical resection ? adjuvant chemotherapy (n = 3) and chemoradiotherapy (n = 1). Median OS of the pure subtype was 60.7 months and that of the combined subtype was 12.1 months (p = 0.02); however, no independent prognostic factor was revealed according to multivariate analysis including the histology subtype (pure vs. combined) and performance status (0–1 vs. 2–4). Although only a small number of patients were included, our analysis revealed some clinical characteristics of ‘‘combined’’ SCLC and suggested that the combined subtype may have inferior survival despite the addition of surgical resection. Recently, chemotherapy for non-SCLC has begun to be individualized based on histology or genetic abnormalities; however, evolution of the treatment of SCLC has stagnated and no personalized approach has been successful for this histology. Interestingly, Fukui et al. retrospectively analyzed 64 consecutive SCLC who underwent surgical resection and reported that 6 patients were identified as the combined subtype with adenocarcinoma (9.3 %) and one patient had an active mutation of epidermal growth factor receptor (EGFR) [5]. We believe that the personalized approach should be mainstream in the future treatment of SCLC, and histological classification might be an important step for the approach. We propose a large-scale study to elucidate the clinical and genetic characteristics of ‘‘combined’’ SCLC. Y. H. Kim (&) M. Mishima Department of Respiratory Medicine Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku 606-8507, Kyoto, Japan e-mail: ekim@kuhp.kyoto-u.ac.jp