Demographics and Clinicopathologic Profile of Pulmonary Sarcomatoid Carcinoma with Survival Analysis and Genomic Landscape

Abstract

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4–16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3–21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7–22.2); surgery, 41.7% (95% CI = 38.9–44.6); radiation, 19.1% (95% CI = 15.1–23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6–32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes.

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review

“…PSC exhibits a high mutation level ( 6 , 7 ) compared to other NSCLC subtypes ( 36 , 37 ) ( Figure 1 ). In their study, Schrock et al reported that the mean tumor mutational burden (TMB) of PSC of 13.6 mutations per megabase (Mb), with 20% of cases having a TMB of >20 mutations/Mb and 43% having a TMB of >10 mutations/Mb ( 38 ).…”

“…The most frequent mutations in PSC are tumor protein 53 ( TP53 ), Kirsten rat sarcoma viral oncogene homolog ( KRAS ), epidermal growth factor receptor ( EGFR ), and mesenchymal to epithelial transition factor ( MET ) ( 7 , 8 , 17 , 36 - 38 , 41 - 44 ). Yang et al performed comprehensive WES of 56 patients with PSC ( 8 ).…”