Clinicopathological and Treatment Patterns of Combined Small-Cell Lung Carcinoma with Future Insight to Treatment: A Population-Based Study

Abstract

Background: Primary lung cancer is the most common cause of cancer-related mortality in the United States (US). Approximately 90% of lung cancers are associated with smoking and the use of other tobacco products. Based on histology, lung cancers are divided into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs). Most SCLCs are of the pure subtype, while the rare combined SCLCs contain elements of both small-cell and non-small-cell morphologies. This study sought to evaluate the demographics, clinical factors, molecular abnormalities, treatment approaches, and survival outcomes with combined SCLC and NSCLCs. Materials and Methods: Data on 2126 combined SCLC patients was extracted from the Surveillance Epidemiology and End Result (SEER) database from 2000 to 2018. Data extracted for analyses included age, sex, race, tumor size, tumor location, metastasis status, stage at diagnosis, treatment received, and treatment outcomes. Multivariate analysis was performed using Statistical Product and Service Solutions (SPSS) software. Results: The patients had a median age of 68 years; 43.9% of the patients were female and 56.1% were male; 84.5% were White and 11.7% were African Americans. The majority of patients had a poorly differentiated disease at 29.6%; 17% were undifferentiated, 3.2% were moderately differentiated, and 0.8% were well differentiated. Chemotherapy was the most common treatment modality (45.3%); 17% underwent surgery only, 10.3% underwent surgery followed by adjuvant chemotherapy, and 10% underwent radiation after surgery. Five-year cancer-specific survival was 15.2% with surgery alone, and combined surgery and chemotherapy provided the highest percentages (38.3% and 34.7%, respectively). Females had significantly higher 1- and 5-year cancer-specific survival rates compared to males (59.3% and 29.9% vs. 48.0% and 23.7, respectively; p < 0.001). Well-differentiated tumors had significantly higher survival compared to other gradings (p < 0.001). Survival decreased as tumor staging moved distally from localized to regional to distant (p < 0.001). Metastasis to bone, liver, brain, and lung significantly decreased survival in comparison to patients who did not have any metastasis (p < 0.001). Females had significantly shorter survival compared to their counterparts when metastasis was to the bone, brain, or liver (p < 0.001). Multivariate analysis identified male sex (Hazard Ratio (HR) = 1.2), undifferentiated grade (HR = 1.9), regional extent of disease (HR = 1.7), distant extent of disease (HR = 3.7), and metastasis to liver (HR = 3.5) as variables associated with worse survival. Conclusion: Combined SCLC is overall very rare. However, the frequency of presentation with combined SCLC is on the rise, in part due to improvements in diagnostic techniques. Despite advances in therapies, treating combined SCLC is challenging, and novel therapies are not utilized, owing to low rates of targetable mutations. Combined SCLC has higher survival rates if well differentiated.

Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: A SEER population-based study

“…Research indicates several factors influencing the prognosis of patients diagnosed with C-SCLC. Key among these is the degree of tumor differentiation, size, and the presence of distant metastases, all of which have been negatively correlated with survival rates [ 3 ]. This underscores the aggressive nature of C-SCLC and its propensity for poorer clinical outcomes compared to P-SCLC.…”

The crosstalk between non-coding RNA polymorphisms and resistance to lung cancer therapies

“…Based on the histological findings, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) are the two main types of lung cancer [ 6 ]. NSCLC, including large cell carcinoma, squamous cell carcinoma, and adenocarcinoma, accounts for approximately 85 % of lung cancer cases.…”

Transformation of adenocarcinoma into small cell lung cancer as one of the mechanisms of acquired resistance to anti-EGFR tyrosine kinase inhibitors

“…Недрібноклітинний (НДКРЛ) і дрібноклітинний (ДКРЛ) раки легень є різними злоякісними захворюваннями зі специфічним фенотипом і молекулярним профілем. Разом із тим, ці форми раку можуть виникати синхронно та метахронно в одного і того самого пацієнта; це свідчить про наявність спільних стовбурових плюрипотентних клітин походження [1,2].…”