ESMO E-Learning: The Evolving Landscape of Extensive Stage Small Cell Lung Cancer

In this module, the authors cover the epidemiology, pathology, biology, molecular classification of small cell lung cancer (SCLC) and state of the art in terms of treatment of extensive stage (ED) SCLC before immunotherapy; they elaborate the new treatment paradigm based on evolving immune checkpoint inhibitors and discuss the future outlook, especially in terms of exploring biomarkers and combination strategies. The module provides a comprehensive overview of current treatments and future landscape in different settings of ED SCLC.

SCLC represents 10-15% of all lung cancers. Its incidence decreased in the last decade in Europe. It is a highly smoke-related tumour with increased prevalence among elderly patients. It is the most aggressive form of lung cancer with dismal prognosis. There were no significant improvements in this field for a long time and recent advances in immunotherapy represent a new paradigm.

In the module, the authors detail about the state of the art in the management of ED SCLC before immunotherapy by elaborating the treatment strategy and the role of platinum, the role of thoracic radiation, the role of prophylactic cranial irradiation (PCI), and treatment of relapsed/refractory disease. Furthermore, they state about a plethora of failed anticancer treatment strategies.

The part on the new immunotherapy paradigm starts by mentioning the old ineffective immunotherapies and elaborating the question if SCLC is an immune excluded tumour. The authors further elaborate PD-L1 expression in SCLC, data from the clinical trials with novel immune checkpoint inhibitors in first-line setting, as maintenance after first-line chemotherapy, second-/third-line and beyond, in the treatment of ED SCLC.

The authors further elaborate a number of significant upcoming scientific questions, such as the identification of immunotherapy biomarkers, the role of PCI and thoracic radiation therapy with immunotherapy, stereotactic radiosurgery for the treatment of brain metastases, that could reduce toxicity of the whole brain radiotherapy, as well the investigation of DDR inhibition especially for potential synergism with immunotherapy. Although DLL3 targeting did not prove effective, it remains an appealing target. Future study designs could consider different treatment strategies depending on molecular SCLC groups. The authors also provide a hint of potential personalised treatment, by stating that modern molecular classification of SCLC may serve for potential targeted treatment in patients with SCLC.