Small Cell Lung Cancer

Background

• General information:
  • Small cell lung cancer is a malignant epithelial tumor consisting of small cells with scant cytoplasm, ill-defined cellular borders, finely granular nuclear chromatin, and absent or inconspicuous nucleoli.
  • It is characterized by rapid doubling time, high growth fraction, and widespread metastases early in disease; patients often present with hematogenous metastases.
  • World Health Organization (WHO) classifies small cell lung cancer as a neuroendocrine tumor; it can be further classified as pure small cell lung cancer or combined small cell lung cancer.
  • Small cell lung cancer is suspected in patients with a history of cigarette smoking, coughing, hemoptysis, wheezing, fever, dyspnea, and/or chest pain.
• Epidemiology:
  • An estimated 228,150 new cases of lung and bronchus cancer are expected worldwide in 2019. Small cell lung cancer accounts for about 13%-15% of lung cancer cases.
  • The annual incidence has decreased over the past 30 years in industrialized countries, likely due to decreased rate of smoking in these regions.
  • From 2009 to 2015 there were 33,824 total cases of small cell cancer of lung or bronchus in the United States; of these, about 75% of patients had metastatic disease at diagnosis.
  • The most common risk factor for small cell lung cancer is cigarette smoking.

Evaluation

• The initial evaluation to establish diagnosis includes:
  • blood tests (Strong recommendation)
  • chest x-ray
  • IV contrast-enhanced computed tomography (CT) of chest, abdomen, and pelvis or of chest extending through liver and adrenal glands (Strong recommendation)
• Confirm the diagnosis in patients with radiographic/clinical evidence of small cell lung cancer with the least invasive biopsy/pathology method as dictated by the patient’s presentation (Strong recommendation). Options include sputum cytology, thoracentesis, bronchoscopy including transbronchial needle aspiration (TBNA), fine needle aspiration (FNA), and transthoracic needle aspiration (TTNA).
• Pretreatment testing aimed at staging typically includes:
  • brain magnetic resonance imaging (MRI) preferred or IV contrast-enhanced brain CT to detect brain metastases (Strong recommendation);
  • bone scan (Strong recommendation);
  • positron emission tomography (PET)/CT from skull base to mid-thigh if suspect limited stage or need clarification of stage (Weak recommendation).
• Additional workup (if it is not done previously) for suspected limited stage disease includes:
  • pulmonary function tests in patients being evaluated for surgery or definitive radiation therapy (Weak recommendation);
  • bone MRI or x-ray if PET/CT is inconclusive, followed by bone biopsy if MRI or bone scan is inconclusive (Weak recommendation);
  • head MRI or CT in addition to PET, or abdominal CT plus bone scan in patients with clinical stage I disease considering definitive surgery (Strong recommendation);
  • thoracentesis with cytologic analysis if pleural effusion is present (Strong recommendation) and can be safely accessed;
  • bone marrow aspiration and biopsy in select patients with presentation suggestive of bone marrow invasion, including signs of blood-bone marrow barrier rupture (such as nucleated red blood cells on peripheral blood smear [peripheral blood erythroblasts]), or abnormal blood count (such as neutropenia and thrombocytopenia) (Weak recommendation).
• Additional workup for never smokers with extensive stage disease includes molecular profiling to clarify diagnosis and evaluate possible targeted therapies (Weak recommendation).

Management

Management of Limited Stage Disease

• If limited stage disease and negative pathologic mediastinal staging, perform lobectomy and mediastinal lymph node dissection or sampling (Weak recommendation), then follow with adjuvant treatment, based on findings from lymph node dissection or sampling.
  • If lymph nodes are negative, offer 4 cycles of systemic therapy (Weak recommendation).
  • If lymph nodes are positive, offer sequential or concurrent systemic therapy with or without mediastinal radiation therapy (Weak recommendation).
• If limited stage disease and positive pathologic mediastinal imaging or limited stage disease in excess of T1-T2, N0:
  • for performance status (PS) 0-2, offer initial treatment with concurrent systemic therapy plus thoracic radiation therapy (Strong recommendation);
  • for performance status 3-4 due to small cell lung cancer, offer systemic therapy with or without either concurrent or sequential radiation therapy (Weak recommendation);
  • for performance status 3-4 not due to small cell lung cancer, offer an individualized treatment plan, including use of supportive care (Weak recommendation).
• If limited stage disease and medically inoperable or decision not to pursue surgical resection, options include either stereotactic ablative radiation therapy (SABR) followed by adjuvant systemic therapy or concurrent chemoradiation (Strong recommendation).
• Offer adjuvant prophylactic cranial irradiation to patients with limited stage disease and a complete or partial response to initial therapy (Strong recommendation).

Management of Extensive Stage Disease

• For patients with extensive stage disease:
  • If no localized symptomatic sites or brain metastases, offer supportive care and base additional treatment on performance status.
    • For performance status 0-2 or 3-4 due to small cell lung cancer, offer combination systemic therapy (Strong recommendation).
    • For performance status 3-4 not due to small cell lung cancer, may offer an individualized treatment plan and consider best supportive care (Weak recommendation).
  • If localized symptomatic sites with superior vena cava syndrome, lobar obstruction, or bone metastases, treatment options include:
    • systemic therapy with or without radiation therapy to symptomatic sites (Weak recommendation);
    • orthopedic stabilization and palliative external beam radiation therapy, for patients with high risk of fracture due to osseous impairment (Weak recommendation).
  • If spinal cord compression, consider radiation therapy to symptomatic sites before systemic therapy (unless immediate systemic therapy is indicated) (Weak recommendation).
  • If brain metastases:
    • consider systemic therapy before brain radiation therapy if patient is asymptomatic (Weak recommendation);
    • consider brain radiation therapy before systemic therapy (unless immediate systemic therapy is indicated) if patient is symptomatic (Weak recommendation).
  • For patients with a complete or partial response to initial therapy, options include adjuvant prophylactic cranial irradiation (Weak recommendation) or magnetic resonance imaging (MRI) surveillance of brain (Strong recommendation). May also offer sequential thoracic radiation therapy after systemic therapy, particularly in those with residual thoracic disease and low-bulk metastatic disease (Strong recommendation).

Surveillance

• Surveillance for patients with small cell lung cancer includes (Strong recommendation):
  • routine history and physical with assessment of symptoms
  • computed tomography (CT) of chest, abdomen, and pelvis
  • MRI or CT of brain
  • intervention for smoking cessation
  • survivorship care plan

Management of Relapsed or Progressive Disease

• Offer palliative management of symptoms to all patients with relapsing or progressive disease at any time during treatment regardless of PS, including localized radiation therapy to symptomatic sites (Strong recommendation).
• For patients with relapsing or progressive disease and PS 0-2, offer subsequent systemic therapy with response assessment by chest/abdomen/pelvic CT with contrast after every 2-3 cycles (Strong recommendation).
  • If response, continue therapy until disease progression or unacceptable toxicity (Strong recommendation).
  • If no response or unacceptable toxicity and PS remains 0-2, options include subsequent systemic therapy and palliative management of symptoms including localized radiation therapy to symptomatic sites (Strong recommendation).