Small cell lung cancer (SCLC) is a highly aggressive disease, often diagnosed at an advanced stage and with limited treatment options. In recent years, immunotherapy has been approved in combination with chemotherapy in the first line setting of extensive stage disease (ES-SCLC). However, only 10-15 % of patients with ES-SCLC treated with chemoimmunotherapy (CT-IO) experience a long-term benefit. In addition, patients are often clinically frail due to advanced age, comorbidities, and disease-related symptoms, making SCLC a challenging condition. Real-world evidence (RWE) becomes particularly valuable in this scenario, not only to confirm the results of pivotal trials, but also to evaluate the outcomes of CT-IO in populations that are generally excluded from clinical trials. RWE could also define the role of integrative treatments such as thoracic consolidation radiotherapy and prophylactic cranial irradiation, which are used in selected patients in the clinical practice but were scarcely applied in pivotal trials. In this review, we focused on RWE in ES-SCLC, with the aim of improving clinical decision making. Notably, real-world data have largely confirmed the efficacy and safety of CT-IO observed in pivotal clinical trials, with a possible benefit even in more fragile patients. However, these studies also highlight that a significant proportion of the ES-SCLC population remains untreated due to poor clinical conditions.
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