Small-Cell Carcinoma

Small-cell carcinoma, also known as small-cell lung cancer (SCLC) or oat-cell carcinoma, is a highly malignant cancer that predominantly arises in the lung but can also occur in other organs such as the cervix, prostate, and gastrointestinal tract. It is more aggressive than non-small cell carcinoma, characterised by a shorter doubling time, higher growth fraction, and earlier metastasis. SCLC is strongly associated with tobacco smoking, and its prognosis remains poor, with a 10-year relative survival rate of only 3.5%.

Signs and Symptoms

SCLC usually presents in the central airways, leading to narrowing of bronchial airways. Symptoms include chronic cough, dyspnea, weight loss, and general debility. Over 70% of patients present with metastatic disease, commonly affecting the liver, adrenals, bone, and brain. Due to its neuroendocrine nature, SCLC can produce ectopic hormones like adrenocorticotropic hormone (ACTH) and antidiuretic hormone (ADH), leading to paraneoplastic syndromes such as the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) and Lambert–Eaton myasthenic syndrome (LEMS).

Diagnosis

Diagnosis of SCLC involves imaging studies and histopathological examination. At diagnosis, 60-70% of patients already have metastases. A histopathologic image of SCLC typically shows cells smaller than normal with minimal cytoplasm.

Types of SCLC

Limited Stage (LS-SCLC)

In LS-SCLC, the cancer is confined to one lung and nearby lymph nodes. Treatment typically includes combination chemotherapy (cisplatin or carboplatin plus etoposide) and concurrent chest radiotherapy. Despite high initial response rates, relapse is common, and median survival is 18 to 24 months.

Extensive Stage (ES-SCLC)

ES-SCLC involves metastasis beyond the thorax. Platinum-based combination chemotherapy is the standard treatment, with radiotherapy added to palliate symptoms. Despite high response rates, the duration of response is often short.

Treatment

Chemotherapy

Chemotherapy regimens commonly used for SCLC include cisplatin and etoposide, or carboplatin and etoposide. For cisplatin-resistant cases, paclitaxel may be effective. Newer agents like lurbinectedin have shown promise in relapsed SCLC.

Immunotherapy

Three immunotherapies have been approved by the FDA for SCLC: nivolumab, atezolizumab, and tarlatamab. However, the high cost of some treatments has led to funding controversies in countries like Canada and the UK.

Radiation Therapy

Chest radiation improves survival in SCLC patients by killing cancer cells and preventing recurrence. Prophylactic cranial irradiation is also used to prevent brain metastases in patients who respond well to initial treatment.

Relapse Treatment

For relapsed SCLC, treatment options include cyclophosphamide, doxorubicin, vincristine, paclitaxel, and irinotecan. Patients who relapse more than six months after initial therapy may be retreated with the original regimen.

Prognosis

The prognosis for SCLC remains poor, with 5-year survival rates ranging from 3.6% to 32.2% for women and 2.2% to 24.5% for men. Long-term survival is rare but possible with aggressive treatment. Recent advances in treatment have modestly improved survival outcomes.

Epidemiology

SCLC accounts for about 15% of lung cancers in the US and occurs almost exclusively in smokers. The incidence and mortality rates have decreased in recent decades.

Genetics

Genetic mutations commonly associated with SCLC include TP53, RB1, PTEN, and MYC amplifications. Loss of heterozygosity on chromosome arm 3p is also frequently observed.

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Self-assessment MCQs (single best answer)

What is another name for Small-Cell Carcinoma?

What is the 10-year relative survival rate for Small-Cell Carcinoma?

Which of the following symptoms is NOT typically associated with Small-Cell Carcinoma?

What percentage of patients present with metastatic disease at the time of Small-Cell Carcinoma diagnosis?

What is the standard treatment regimen for Limited Stage Small-Cell Carcinoma?

Which chemotherapy agents are commonly used in the treatment of Small-Cell Carcinoma?

Which immunotherapy is NOT approved by the FDA for Small-Cell Carcinoma?

What is the typical median survival for patients with Limited Stage Small-Cell Carcinoma?

Which genetic mutation is commonly associated with Small-Cell Carcinoma?

Prophylactic cranial irradiation is used in Small-Cell Carcinoma to prevent: