Small cell lung cancer

Small cell lung cancer (SCLC) is a dangerous disease characterized by rapid growth of the primary tumor and early metastasis.

It occurs in 10-15% of lung cancers.

Causes and risk factors

It is difficult for specialists to name the exact causes of small cell lung cancer. However, a connection can be traced to the following risk factors:

Among all of the above, smoking is the No. 1 cause of small cell lung cancer. Here are just a few facts:

According to foreign researchers, a decrease in small cell lung cancer cases from 25-30% to 15% occurred after the number of smokers decreased.

In women, the disease is currently registered more often than before, which is associated with an increase in the number of female smokers.

Notably, there may be a latent period of 20-25 years from the start of smoking to the onset of lung cancer.

Classification

Size-baased. Small-cell lung carcinomas are divided into:

• small-cell,
• combined small cell.

Stage-based. Prior to the current improvement in lung diseases diagnosis, most cases of small cell cancer were detected late. Therefore, oncologists used a classification that distinguished between localized and advanced stages of the disease.

Nowadays, the international TNM system is used for small cell lung cancer.

• Stage 1. An up to 3 cm mass localized within a lobular bronchus or its segment, without regional or distant metastases. Unfortunately, at this point the lesion is often overlooked, so patients seek help much later.
• Stage 2. A tumor in the lung infiltrates the pleura or large bronchi. Atelectasis may occur (areas of recession, shrinkage of lung tissue, where there is no ventilation, so the lung in this area "does not breathe"). Nearby lymph nodes are affected.
• Stage 3. At this stage of disease development, the neoplasm spreads to the pleura, pericardium, diaphragm, and chest wall. Atelectasis of the whole organ occurs, and metastases develop in the mediastinum and other lymph nodes.
• Stage 4. Small cell lung cancer is characterized by involvement of vertebral bodies, mediastinal organs, main vessels. There are distant metastases.

Disease course

At the beginning, small cell lung cancer is asymptomatic. Then signs appear that may resemble other conditions, but not a lung lesion. Therefore, patients may refer to doctors specializing in other fields.

Early symptoms of a small-cell lung cancer lesion may include:

• intermittent fever up to 37-38°C;
• general weakness and increased fatigue, which is observed as early as before noon;
• headache;
• dizziness;
• dry cough;
• skin itching, manifestations of dermatitis.

Since this type of cancer occurs more often in smokers, the condition is misinterpreted as chronic bronchitis.

As more and more extensive areas of the lungs get affected, more symptoms develop, including:

• shortness of breath;
• spitting of blood;
• dry or moist cough attacks without apparent reason;
• chest pain,
• weight loss;
• poor appetite.

Distant metastases cause function failure in other organs. For example, malignant growth in the brain may result in epilepsy; if the laryngeal nerve is affected, the voice may become hoarse.

Persisting symptoms that increase over time require a comprehensive lung cancer screening.

Small cell lung cancer diagnosis

Before the first symptoms appear. Smokers should have regular chest scans. The frequency of such preventive examinations depends on the number of cigarettes smoked per day, as well as the age, so it is to be determined by the attending physician.  Currently, the most informative type of examination is a low-dose spiral computed tomography, which enables detecting changes inherent to small cell cancer.

When cancer is suspected. The diagnosis is carried out in 3 steps:

• Lung mass imaging - computed tomography.
• Confirmation of morphological diagnosis - biopsy + histological study or puncture of pleural fluid accumulated in the lower chest + cytology.
• Detection of small cell carcinoma distant metastases - abdominal MSCT, PET-CT, brain MRI, bone scan.

Additional laboratory and radiology tests. In small-cell cancer, they provide information about the patient's overall health.

Treatment

In the case of small cell lung cancer, chemotherapy is considered to be the best treatment option. It is supplemented by radiotherapy and, in the initial stages, surgery.

Radical surgery for small cell cancer. It is performed rarely and almost always at early stages. It is often a lobectomy. If the lung is removed completely, postoperative and long-term survival rates are worse. The most encouraging results are achieved by a combination with cytostatic drugs administered before and after surgery.

Radiotherapy is used alongside chemotherapy to increase the effectiveness of treatment. External beam radiation is used. Conventionally, there are 2 types of radiation therapy applied for treatment:

• early – commencing in the first week following the beginning of chemotherapy,
• late - after the third chemo week.

In the former case more encouraging results are observed.

Chemotherapy is administered both for relapsed small cell lung cancer, and as initial therapy. It allows to achieve a stable remission and prolong the life of cancer patients by several months or years, depending on the tumor size and cancer stage.

Currently, the following chemo regimens in combination with radiation therapy are used:

• EP - etoposide + cisplatin.
• IP - irinotecan + cisplatin.
• EC (in elderly and weakened patients) - etoposide + carboplatin.

The above options are more effective in carcinoma treatment as compared to formerly administered drugs.

Prophylactic cranial irradiation is an important component of any lung malignancy therapy plan, which ensures a 2-time increase in the patient survival rate. Therefore, it is performed no matter whether metastases in the brain are present or not.

Ongoing research. Currently, attempts are being made to find effective treatments among targeted (using monoclonal antibodies) drugs, as well as to "train" our own immune cells to fight against the malignant ones. Therefore, it is possible that in the near future there will be tools that will make the fight against this disease even more successful.

Prognosis and follow-up

Thanks to modern diagnostic tools and timely initiated consistent therapy, the SCLC diagnosis is no longer devastating. The reliable methods of small cell carcinoma treatment can bring very good results.

• With consistent therapy at an early stage, 5-year survival is now observed in 40% of patients (previously, almost all cases ended lethally within a very short period of the disease). Moreover, if a complete cancer regression has been achieved, some patients live much longer than 5 years.
• In the case of a local cancer, when the tumor affects only one lung, consistent therapy extends life by 1.5-2 years. By comparison, life expectancy in the case of untreated advanced carcinoma, or when a tumor in the lung becomes immune to ongoing therapy for some reason, is rarely more than 3-4 months.

Follow-up management. After the maximum possible result is achieved, which may include a complete or partial tumor regression in the lung, or tumor stabilization), patients should visit an oncologist once per quarter during the first 2 years, and once per half-year in the following 3-5 years. Exams that are aimed at detecting cancer recurrence include:

• chest X-ray/CT,
• abdominal ultrasound,
• MRI/CT of the adrenal glands.

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Sen Yang, Zhe Zhang , Qiming Wang / Emerging therapies for small cell lung cancer// J Hematol Oncol. 2019 May 2;12(1):47. PMID: 31046803 

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