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KEY CONCEPTS

  • Small cell lung cancer (SCLC) is an aggressive malignancy for which outcomes remain poor. The majority of patients present with metastatic disease, and few patients are cured, even among those that present with early-stage disease. There is an urgent need for more effective therapies for this disease.

  • For patients with stage I disease, surgical resection should be considered if mediastinal staging is negative. Adjuvant chemotherapy with four cycles of etoposide–cisplatin (EP) should be considered for all patients with surgically resected SCLC and no lymph node metastases found at the time of resection.

  • Most patients with limited-stage disease are treated with concurrent chemoradiotherapy. Although carboplatin is frequently used in patients with extensive-stage disease, EP with twice-daily radiation therapy remains the standard of care in patients without contraindications to cisplatin.

  • Numerous clinical trials have established the effectiveness of prophylactic cranial irradiation (PCI) in decreasing the incidence of intracranial disease, although its impact on survival has been variable. All patients with limited-stage disease who respond to treatment should receive PCI. The use of PCI in patients with extensive-stage disease remains controversial.

  • First-line chemoimmunotherapy has recently been shown to improve survival in patients with extensive-stage disease. The development and understanding of biomarkers for response to immunotherapy is progressing and may improve outcomes for some patients.

  • Treatment options are limited for patients with recurrent disease, and clinical trials are recommended when feasible. There are no approved targeted agents for SCLC despite a plethora of trials.

INTRODUCTION

Small cell lung cancer (SCLC) is an aggressive bronchogenic carcinoma representing 14% of all lung cancers, accounting for approximately 30,000 new cases annually in the United States.1 It is distinguished from non–small cell lung cancer (NSCLC) by its rapid doubling time and early metastatic dissemination. Regional lymph node involvement or distant metastasis is present in 90% or more of patients at diagnosis. Historically, SCLC has been staged as limited disease (LD), which is confined to the ipsilateral thorax of origin and regional nodes, versus extensive disease (ED). The recent International Association for the Study of Lung Cancer (IASLC) staging project and American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC), eighth edition, suggest use of the tumor, node, metastasis (TNM) system for the staging of SCLC.2 Clinically, the limited- and extensive-stage classification is practical given that most patients present with advanced disease (stages III–IV) and are rarely candidates for resection or other definitive therapies.

Standard treatment for patients with LD (stages I–IIIB) includes both chemotherapy and radiation; chemotherapy is the mainstay of treatment for ED (stage IV). Although a dramatic response to initial therapy is usually observed, more than 95% of patients with ED and 80% to 90% of those with LD eventually have a relapse and die of their disease.

Despite extensive research, few substantive advances in the systemic treatment of patients with SCLC have been made for decades. However, molecular profiling and preclinical models of SCLC ...

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