Clinical features and prognostic factors of combined small cell lung cancer: development and validation of a nomogram based on the SEER database

Lan Yang; Yuwen Zhou; Gang Wang; Dan Liu; Bojiang Chen; Dan Pu; Pierpaolo Correale; Dirk Rades; Yusuke Tomita; Alessandro Inno; Mariacarmela Santarpia; Yalun Li; Weimin Li

doi:10.21037/tlcr-21-804

Clinical features and prognostic factors of combined small cell lung cancer: development and validation of a nomogram based on the SEER database

Transl Lung Cancer Res. 2021 Nov;10(11):4250-4265. doi: 10.21037/tlcr-21-804.

Authors

Lan Yang^#¹, Yuwen Zhou^#², Gang Wang³, Dan Liu¹, Bojiang Chen¹, Dan Pu¹, Pierpaolo Correale⁴, Dirk Rades⁵, Yusuke Tomita⁶, Alessandro Inno⁷, Mariacarmela Santarpia⁸, Yalun Li^#⁹, Weimin Li^#^{1

10}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
² Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Respiratory and Critical Care Medicine, Clinical Research Centre for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China.
⁴ Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.
⁵ Department of Radiation Oncology, University of Lübeck, Lübeck, Germany.
⁶ Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁷ Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR), Italy.
⁸ Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy.
⁹ Department of Respiratory and Critical Care Medicine, Lung Cancer Treatment Center, West China Hospital, Sichuan University, Chengdu, China.
¹⁰ Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Combined small-cell lung cancer (CSCLC) refers to the simultaneous presence of small cell lung cancer (SCLC) and any subtype of the non-small cell lung cancer (NSCLC). This study aimed to explore the prognosis of CSCLC, NSCLC, and pure SCLC patients, and to develop a nomogram to estimate the overall survival (OS) for CSCLC patients.

Methods: Patients diagnosed with NSCLC, CSCLC, and pure SCLC between 2004 and 2015 were identified from the Surveillance Epidemiology and End Results (SEER) database. Survival analyses were performed by using the Kaplan Meier curves and Cox proportional hazards regression. All CSCLC patients were randomly split 7:3 into training and validation sets. A nomogram was developed by integrating all independent predictors for OS. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability.

Results: A total of 326,695 lung cancer patients, including 871 with CSCLC, 280,391 with NSCLC, and 45,433 with pure SCLC were enrolled. CSCLC was associated with worse survival compared with NSCLC both in the unmatched and matched cohorts. However, compared to pure SCLC, CSCLC was associated with significantly better survival in the unmatched cohorts only, while showed marginally non-significantly better survival after propensity score matching (PSM). For CSCLC, a nomogram was constructed for the 6-month, 1-year, and 3-year OS prediction by combining the independent risk factors, including age, gender, tumor, node, and metastasis stage, surgery, and chemotherapy. The nomogram showed good discrimination and calibration both in the training and validation sets, and better performance than the tumor-node-metastasis staging system. Risk stratification analysis indicated that the nomogram scores efficiently divided CSCLC patients into low-, intermediate-, and high-risk groups (P<0.001).

Conclusions: CSCLC patients presented a significantly worse prognosis than patients with NSCLC, but comparable prognosis when compared with pure SCLC patients in the matched cohorts. In addition, we developed and validated a nomogram for predicting the 6-month, 1-year, and 3-year OS in CSCLC patients.

Keywords: Combined small cell lung cancer (CSCLC); nomogram; prognosis; propensity-score matching (PSM); the Surveillance Epidemiology and End Results (SEER).