Update on Small-Cell Lung Cancer - Episode 1
Transcript: Stephen Liu, MD: Small-cell lung cancer typically presents with fairly fulminant symptoms, usually a subacute history over the past few months. This is not typically something that’s picked up incidentally. Small-cell lung cancer is characterized by a fairly aggressive biology, so patients typically have pretty notable symptoms. This primarily includes a central tumor, so they would have symptoms of obstruction, trouble breathing, difficulty swallowing, and changes in voice related to involvement of the recurrent laryngeal nerve. Weight loss and fatigue are commonly involved. And patients often present with symptoms from different metastases, such as painful bony lesions or symptomatic brain metastases. This is a disease with a fairly fulminant presentation, and it is not unusual for us to diagnose patients in the emergency department and need to start therapy quite quickly.
Staging for small-cell lung cancer still follows the AJCC [American Joint Committee on Cancer] TNM staging system. They designed a score based on the tumor size, degree of invasion, location, the location of lymph nodes involved, and the presence or absence of different metastases. We’re currently using the eighth staging system from AJCC. This is correlated with prognosis. This is what would show up on standardized tests and SEER [Surveillance, Epidemiology, and End Results] data.
However, functionally, most practices would use the VALSG [Veterans Administration Lung Cancer Study Group] modified lung staging system. This would separate small-cell lung cancer into two stages, an earlier, limited stage or limited disease and a later, extensive-stage or extensive disease. This is more of a functional staging system used to guide initial therapy and proves to be a little more valuable clinically. Limited-stage disease would be small-cell lung cancer, where all the disease could be encompassed within 1 tolerable radiotherapy port. This would exclude any malignant effusions or distant metastases. Extensive-stage disease would be anything that’s not limited-stage disease.
About a third of patients will present with limited-stage disease, and the rest will present with extensive-stage disease. With limited-stage disease, we can deliver definitive chemoradiation therapy, and there’s the prospect for long-term survival, potentially cure, but for a subset of patients. For extensive stage disease, unfortunately long-term survival is not really expected. The standard therapy would be systemic-treatment chemotherapy and more recently, chemoimmunotherapy. The interesting thing about the staging system is that because it is functional, it will vary a bit. For limited-stage disease, a tolerable radiotherapy port can be defined differently by different radiation oncologists and will be different based on the specific clinical circumstance. If a patient had a very poor DLCO [diffusing capacity of lung for carbon monoxide], was on a high level of oxygen, and had underlying pulmonary fibrosis, they may not be a candidate for radiation. No radiation port would be tolerable. That person, even if they had a small amount of disease, would classify as extensive-stage disease.
Small-cell lung cancer can initially cause several clinical complications. Presentation can be fairly fulminant, and patients can have quite a high burden of disease. Symptomatic brain metastases and seizures can be seen. Patients can develop respiratory failure requiring ventilator support even before a diagnosis is made.
An interesting form of presentation for small-cell lung cancer is paraneoplastic syndromes. This disease in particular has a high association with paraneoplastic syndromes. It comes in two varieties: endocrine syndromes and neurological syndromes. The endocrine syndromes—such as SIADH [syndrome of inappropriate antidiuretic hormone secretion], which will typically include low sodium, hypercalcaemia, and weight loss related to cachexia-inducing molecules—often mirror the course of the disease. It’s not unusual for us to see those improve with the treatment of the underlying cancer.
Neurologically mediated paraneoplastic syndromes are a little more challenging. These can be devastating. Stiff-man syndrome, retinal blindness, limbic encephalitis, these are typically antibody mediated because of crosstalk between an antibody recognizing an antigen on the tumor and 1 that interacts with neuronal cells. These symptoms and the consequences of these paraneoplastic syndromes unfortunately may not improve with treatment of cancer. The antibody may persist, and even though the cancer may be under very good control, the paraneoplastic syndrome can really have a negative impact on quality of life.
It is interesting that patients with paraneoplastic syndrome, particularly those neurological paraneoplastic syndromes, do seem to have better prognoses, and this may be related to, in essence, the immune system effectively targeting a cancer with the unfortunate consequence of targeting neuronal cells and causing, as we said, very dramatic symptoms.
Transcript Edited for Clarity