Small cell lung cancer

Epidemiology and risk factors

There is an undeniable relationship between SCLC and tobacco use; SCLC is quite uncommon in nonsmokers, which account for <5% of new SCLC cases. As a result, the incidence of SCLC varies dramatically by geography, closely mirroring the demographics of tobacco use. In the United States overall, the incidence of SCLC is decreasing. In 1986, 17% of new lung cancer cases were classified as SCLC and the proportion steadily rose, peaking in 1993 when SCLC represented 25% of lung cancer diagnoses. The number has since decreased and plateaued around 15%, attributed to changes in smoking habits. Similarly, the demographics of SCLC have shifted in accord with smoking trends. In 1973, only 28% of SCLC cases were diagnosed in women. By 2002, women were as likely to be diagnosed with SCLC as men, with 50% of new cases seen in female patients. Though accounting for a minority of lung cancer cases, SCLC remains a pressing public health burden as the survival rates for SCLC are significantly lower than those of adenocarcinoma or squamous cell carcinoma, in the United States and globally. Due to the high rates of tobacco consumption across the world, SCLC promises to remain extremely relevant in the years to come.

Presenting symptoms

SCLC typically originates near the central airways but spreads quickly. Approximately 90% of new SCLC diagnoses are stage III or IV disease. Most patients with SCLC are symptomatic at diagnosis. Symptoms can arise from direct locoregional growth or from distant spread. Rapid central growth often leads to bronchial obstruction with symptoms such as dyspnea, cough, hemoptysis, or recurrent pneumonia. Because most patients with SCLC have a smoking history and may carry comorbid diagnoses such as chronic obstructive pulmonary disease, respiratory symptoms may be improperly attributed to worsening emphysema, often delaying diagnosis. Obstruction of vasculature can lead to superior vena cava syndrome, where venous return is impeded by the tumor, leading to swelling of the face, neck and upper extremities, and, in extreme cases, papilledema and cerebral edema. Other symptoms related to primary growth include hoarseness from compromise of the recurrent laryngeal nerve and dysphagia from compression of the esophagus.

Most patients with SCLC will have metastases at the time of diagnosis and may present with symptoms related to those distant metastases ( Fig. 14.1 ). This may include pain or pathological fracture from osseous involvement. Liver metastases, depending on degree, may lead to abdominal pain, abnormal blood tests, or obstructive jaundice. Brain metastases are relatively common in SCLC, present at diagnosis in about 10% of patients with a cumulative risk of up to 80% by 2 years. Symptoms vary by size and location, but metastases can lead to headaches, nausea, vision disruption, personality changes, or seizures.

Early-stage SCLC is uncommon but may be detected incidentally. Screening studies have had little impact on SCLC. The National Lung Screening Trial demonstrated computed tomography (CT)–based screening yielded a 20% reduction in lung cancer mortality, but this survival benefit was primarily driven by NSCLC. Among the 143 identified SCLC cases, only 49 (34.2%) patients were detected at screening; most cases were detected outside of the screening protocols. Perhaps reflecting the poor overall prognosis, there was no difference in survival between the screen-detected cases and cases detected outside of screening; 89% of detected cases were late stage (III/IV).

Paraneoplastic syndromes

SCLC is also associated with both endocrine and neurological paraneoplastic syndromes, whose detection may precede the cancer diagnosis. Paraneoplastic endocrine syndromes are the result of pathologically synthesized peptides or hormones. The syndrome of inappropriate secretion of antidiuretic hormone is seen in about 11% of SCLC diagnoses and typically presents with euvolemic hyponatremia. Excess secretion of adrenocorticotropic hormone can lead to Cushing syndrome, characterized by hypertension, hypokalemia, moon facies, and proximal muscle weakness. The presence of either syndrome of inappropriate secretion of antidiuretic hormone or Cushing syndrome has been associated with poorer survival. Paraneoplastic neurological syndromes are the result of antibodies generated against a tumoral antigen that cross-react with components of the nervous system. Many of these syndromes have been described including encephalitis (mediated by anti-Hu antibodies), Lambert-Eaton syndrome (mediated by anti-voltage-gated calcium channel antibodies), retinal blindness (mediated by antirecoverin antibodies), and stiff-person syndrome (mediated by antiamphiphysin antibodies). While paraneoplastic neurological syndromes are relatively uncommon, the autoantibodies (at lower titers) can be detected in a substantial fraction of patients with SCLC who do not have the characteristic neurological symptoms. ^, Though these neurological syndromes can have a devastating effect on quality of life, they have also been associated with a better prognosis.