Small cell lung cancer (SCLC) is an aggressive form of lung cancer, accounting for 10% to 15% of all diagnoses. It grows rapidly and tends to spread quickly to other parts of the body. SCLC is highly associated with heavy tobacco smoking. Its swift progression often leads to diagnosis at an advanced stage.
Defining Extensive Stage Small Cell Lung Cancer
Healthcare providers categorize small cell lung cancer into two main stages: limited stage and extensive stage. Extensive stage small cell lung cancer (ES-SCLC) indicates that the cancer has spread widely beyond a single area that can be effectively treated with radiation within one side of the chest. This spread can involve the other lung, lymph nodes on the opposite side of the chest, or distant organs throughout the body.
Common sites for widespread metastasis include the liver, bones, brain, and adrenal glands. The presence of malignant fluid around the lungs (pleural effusion) or heart (pericardial effusion) also classifies the disease as extensive stage. A significant majority of individuals, approximately 60% to 70%, are diagnosed with extensive stage disease at the time of their initial presentation.
Symptoms and Diagnostic Process
Symptoms of extensive stage small cell lung cancer often manifest as the disease progresses. Common signs related to the primary tumor include a persistent cough that may worsen, chest pain, shortness of breath, and hoarseness. Systemic symptoms, which affect the entire body, frequently include unexplained weight loss, fatigue, and a diminished appetite.
When the cancer spreads, specific symptoms can arise depending on the affected site. Bone pain may indicate spread to the bones, while headaches, confusion, seizures, or balance issues can signal brain metastases. Spread to the liver might cause jaundice, and swelling in the face or neck, along with prominent veins, can result from superior vena cava syndrome.
The diagnostic process usually begins with a chest X-ray. If abnormalities are found, further imaging tests are ordered. These include computed tomography (CT) scans to assess tumor spread, and positron emission tomography (PET) scans for staging. Magnetic resonance imaging (MRI) is often used for detailed evaluation of potential brain metastases. Confirmation of SCLC cell type and staging is achieved through a biopsy. Tissue samples are collected via procedures like a needle biopsy or bronchoscopy for microscopic examination.
Primary Treatment Protocols
The primary objective of treatment for extensive stage small cell lung cancer is palliative, aiming to control disease progression, alleviate symptoms, and extend life. The standard first-line systemic treatment involves a combination of platinum-based chemotherapy and immunotherapy. Chemotherapy regimens commonly pair etoposide with either cisplatin or carboplatin, with carboplatin often chosen due to its generally more manageable side effect profile compared to cisplatin.
Immunotherapy drugs, specifically programmed death-ligand 1 (PD-L1) inhibitors like atezolizumab or durvalumab, are administered alongside chemotherapy. These agents help the body’s immune system recognize and fight cancer cells. Treatment is typically delivered in cycles, often consisting of four to six rounds of chemotherapy.
Following the initial chemotherapy cycles, immunotherapy may be continued as a maintenance therapy to help sustain the treatment response. If the cancer progresses after initial treatment, second-line options become necessary. Topotecan is a common choice for relapse occurring within a few months of first-line therapy. Lurbinectedin is another approved agent, particularly for patients with a longer interval without chemotherapy. For those whose cancer returns after a more prolonged period, rechallenging with the initial first-line regimen may be considered, and other chemotherapy combinations like cyclophosphamide, doxorubicin, and vincristine (CAV) are also available.
Role of Radiation Therapy
In extensive stage small cell lung cancer, radiation therapy’s primary role is palliative, focusing on relieving symptoms caused by the cancer’s presence or spread. For example, radiation to the chest can help manage symptoms such as persistent coughing, difficulty breathing due to airway obstruction, or bleeding from the main tumor. Radiation therapy is also directed to specific sites of metastasis, such as bones, to alleviate pain, or to the brain to mitigate neurological symptoms caused by brain metastases.
Prophylactic Cranial Irradiation (PCI) is a distinct application involving preventative radiation to the brain. Given SCLC’s high propensity to spread to the brain, PCI aims to reduce the risk of future brain metastases. This measure is typically considered for individuals who have demonstrated a good response to initial systemic chemotherapy. However, the role of PCI is sometimes debated in the current era of immunotherapy, with ongoing discussions about routine MRI surveillance as an alternative strategy.
Prognosis and Emerging Therapies
The prognosis for individuals diagnosed with extensive stage small cell lung cancer is guarded. While treatment can significantly improve outcomes, median overall survival with current standard therapies ranges from 7 to 14 months. Without treatment, average survival time is shorter, often between 2 to 4 months.
Despite advancements, the five-year survival rate for extensive stage SCLC remains low, typically 2% to 5%. Most patients will experience a relapse, with only 5% to 10% surviving beyond two years.
Despite these statistics, ongoing research offers hope for future improvements in outcomes. Clinical trials are a significant avenue for accessing new treatments, advancing the understanding and management of this disease.
Emerging therapies include next-generation immunotherapies, such as new checkpoint inhibitors like serplulimab, which are showing promise in combination with chemotherapy. Bispecific T-cell engagers, such as tarlatamab, represent another innovative approach. Tarlatamab targets a protein called DLL3 found on many SCLC cells, bringing the body’s T-cells closer to cancer cells for destruction. This drug has received accelerated approval for previously treated SCLC and is being investigated for earlier use.
Researchers are also exploring new targeted therapies and novel combinations of existing drugs, including adding anti-angiogenesis agents to chemo-immunotherapy, and leveraging molecular profiling to develop more personalized treatment strategies.