Treatments for Combined Small Cell Lung Cancer Patients

Jiaxi He; Songhui Xu; Hui Pan; Shuben Li; Jianxing He


Transl Lung Cancer Res. 2020;9(5):1785-1794. 

In This Article

Abstract and Introduction


Background: Combined small cell lung cancer (CSCLC) is a subtype of small cell lung cancer (SCLC) which contains both components of SCLC and non-small cell lung cancer (NSCLC). The prognostic outcomes and treatment strategy of it are still unclear. A large-scale retrospective study was performed to investigate proper treatments for CSCLC.

Methods: All cases of CSCLC were identified from the SEER database during the period of 2004–2016. Clinical characteristics, first-line treatments, surgical procedures and survival data including overall survival (OS) and cancer-specific survival (CSS) were analyzed.

Results: A total of 37,639 SCLC patients were identified. CSCLC accounted for 2.1% (784/37,639). The mean age of CSCLC cohort is 67.3±9.9 years old. Male and white ethnicity patients were accounted for larger proportions (55.7% and 80.4%). The oncological characteristics of CSCLC were consistent with SCLC that most of patients were diagnosed as higher grade and advanced stages. The prognosis of CSCLC was better than SCLC but worse than NSCLC in IA-IIIA stages. No difference was observed in IIIB-IV. Surgery was beneficial in IA-IB stage CSCLC. Adjuvant chemotherapy seemed to have few effects on early stage patients. Trimodality treatment could significantly improve OS in IIA-IIIA CSCLC patients. Chemotherapy-based treatment is predominant choice in advanced stage patients.

Conclusions: CSCLC is a rare and special subtype of SCLC. It has better survival outcome than non-CSCLC in early stage. Surgical treatment is crucial in early stage of CSCLC. Prognostic improvement might be achieved from trimodality treatment in stage IIA-IIIA. Chemotherapy-based treatments should be considered in advanced stage. The effect of surgical treatments in advanced stage patients should be further investigated.


According to the World Health Organization (WHO) Histology Criteria 2015, combined small cell lung cancer (CSCLC) is categorized as a subtype of small cell lung cancer (SCLC).[1,2] It is diagnosed via pathological specimen containing SCLC component and any other malignant components including adenocarcinoma (AD), squamous cell carcinoma (SQ) and large cell carcinoma. Some rare histological types, such as giant cell carcinoma, spindle cell carcinoma and sarcomatoid malignancy, also can be seen in CSCLC. It can be diagnosed regardless of cell amounts when SCLC coexisting with AD, SQ or sarcomatoid carcinoma. In terms of large cell carcinoma, at least 10% of large cell carcinoma component should be observed to make the diagnosis.[2,3] In the previous studies, more than two components of NSCLC were reported in CSCLC.[3]

The previous studies indicated that CSCLC accounted for 5–14% of SCLC.[4–8] The actual incidence may be higher than the previous report because most of CSCLC cases were diagnosed from surgical specimens. The biopsy specimens from CT-guided thoracentesis, bronchoscopy and EBUS are difficult to conclude proper diagnosis. Some retrospective studies showed that CSCLC shared similar characteristics and epidemiological features with SCLC. Besides male and smoking patient predominance, most cases of CSCLC belonged to advanced stages when they were firstly diagnosed. Zhang et al. reported almost 90% of CSCLC were diagnosed as stage III and IV in their cohort.[9]

Referring to the treatments for SCLC, platinum-based etoposide chemotherapy with/without radiotherapy is recommended for SCLC patients in advanced stages by the National Comprehensive Cancer Network (NCCN) guidelines. Surgical treatment is always a controversial topic in early stage of SCLC. A few previous studies reported no prognostic difference was observed between surgical and non-surgical treatment SCLC patients. Some of them even reported worse outcomes in surgical groups.[10–13] Most of these studies included stage II and III patients or ignored the effect of adjuvant chemotherapy. Yang et al. reported that pT1-2N0M0 SCLC patients could be beneficial from adjuvant chemotherapy with/without cranial irradiation.[14] Moon and his colleagues reported that surgery with chemoradiation provided better cancer-specific survival (CSS) in T1-2N0-1M0 SCLC while CSCLC patients might benefit from multimodality.[8] The optimal treatments for CSCLC in each stage are not fully verified.

We therefore sought to demonstrate the clinical characteristics and prognosis of CSCLC based on a large-size sample. Moreover, we also try to explore the optimal treatment for each stage CSCLC for the sake of better prognosis. We present the following article in accordance with the STROBE reporting checklist (available at