Stage IV lung cancer (carcinoma)

And although in some moments the emotional state of a cancer patient leaves much to be desired, in any situation it is important not to give up, doing everything that can prolong life, relieve pain and improve the general condition.

What does stage IV in lung cancer mean?

A tumor at this stage means that the malignant lesion in the bronchi or directly in the lung tissue has already reached such a size that its cells have penetrated into the blood or lymphatic vessels, disseminated to other organs and given rise to distant metastases, which can already be seen using diagnostic imaging methods - MRI, CT, ultrasound, PET-CT, etc.

Healthcare professionals distinguish 2 subtypes of this stage. The first is 4A, when:

• cancer cells have spread to the cardiac and/or pulmonary serous membranes (pericardium, pleura);
• both lungs are affected by a malignant tumor;
• an accumulation of fluid containing abnormal cells is found in the pericardium or pleura area;
• a distant metastasis is found outside the chest.

Substage 4 B means that there are multiple extrapulmonary (distant) foci of malignancy.

In many cases, stage IV malignancy means that the cancerous mass did not appear yesterday. In almost 85% of patients, it took years or even decades from the time the first NSCLC cell appeared until metastases formed in other parts of the body. And all this time, the body had been holding back the rapid progression of the disease as best it could. Provided it gets help in reducing the size of the malignant tumor by means of chemo-, immunotherapy and other modern treatments, as well as by giving up bad habits, the body may regain the strength to further resist the disease for many months or years.

As for SCLC and aggressive large cell carcinoma developing from non-small cell carcinomas, there must also have been a certain amount of time before it reached Stage IV. For the patient, this means that it is important to consult a knowledgeable specialist without delay, and begin treatment as early as possible. After all, SCLC is quite susceptible to chemotherapy. And at least 1% of patients affected by it live 5 years or more after the diagnosis.

How common is Stage IV lung cancer?

Usually, a tumor at this stage is detected by a primary care doctor - a family doctor or a general practitioner. Less often, it is done by a physician with a subspecialty, such as:

• a physician specializing in tuberculosis,
• a pulmonologist dealing with lung diseases,
• an allergology specialist treating bronchial asthma, and so on.

It is only after a conventional X-ray or a CT scan has revealed signs of tumor growth, that the patient is referred to a cancer doctor for further examination and diagnosis confirmation. That is why patients with malignant tumors in the lung tissue, pleura or bronchi are very often treated for bronchitis, pneumonia, tracheitis and other diseases for quite a long time, missing the opportunity to detect the condition in an early stage.

On the other hand, it is still not uncommon for people to be back on their health check-up schedules. In the absence of symptoms, one simply does not get to know that they have cancer.

Taken together, these factors result in the fact that in about one third of patients (according to some authors, up to 36%) malignant lung tumors are first detected when they have already reached Stage IV.

Disease signs

Starting from the moment the first malignant cell appears in the lung tissue, cancer development goes through several stages:

• The tumor is still so small that it is not detected by any currently available laboratory or radiology studies. One is feeling well, and no abnormalities are found during examination.
• The neoplasm can be seen only by ultrasound, MRI, CT scan, or by other diagnostic tools. For example, a cancerous node may accidentally be detected in the bronchi during a bronchoscopy done for a completely different disease. Usually, patients do not notice any decline in health during this period.
• Clinical symptoms appear, which often becomes a reason to visit the doctor.

In the case of a stage IV tumor, the disease has already passed all these stages of development up to the last one: a patient notices local and general symptoms of the cancer progression, and the primary focus itself, as well as daughter neoplasms in other organs are easily detected by imaging tests.

It is noteworthy that lung cancer patients with a long history of smoking, the cough is chronic. Therefore, if it becomes different, even in the last stages it is sometimes not taken as a warning sign, and visits to the doctor are postponed.

General signs of malignant conditions (a paraneoplastic syndrome) include:

• abnormal blood test results (anemia, hypercoagulability, increased numbers of white blood cells, platelets, eosinophils);
• musculoskeletal system abnormalities: hypertrophic osteoarthropathy (bone and joint lesions), muscle inflammation, sometimes also affecting the skin (dermato- and polymyositis);
• endocrine disorders: Cushing's syndrome (excess production of cortisol by adrenal glands);
• mineral metabolism issues: increased levels of calcium in the blood (hypercalcemia).

Additional symptoms may include:

• loss of appetite,
• general weakness,
• increased fatigue,
• sweating,
• occasional fever,
• emaciation (cachexia).

At this cancer stage, there also may be a hoarseness of the voice and difficulty swallowing. Malignant lung masses can be of metastatic origin as well, when the primary focus occurs in other organs of the body: for example, in the case of mammary gland, kidneys, or ENT organs cancer. In such cases the symptoms are characteristic of the neoplasm’s primary localization, and the clinical behavior of the daughter tumors in the lung tissue is usually asymptomatic.

As the disease progresses, there comes a point when the body loses the ability to resist the cancer that has spread through the body, and then multiple organ failure develops, which is characteristic of the terminal stage, during which death occurs. Thanks to modern methods of treatment and successful struggle with distant metastases, it is possible to postpone this event for a rather considerable period of time.

Pleurisy: a specific complication

The pleura is a thin, film-like membrane, one layer of it covering the outside of the lungs, and the other - the inside. They form an airtight interpleural space, allowing them to participate in the act of breathing, keeping pace with the movements of the ribs and diaphragm.

In the case of exudative pleurisy in lung cancer, these layers become inflamed and fluid accumulates between them. As its volume increases in the pleural cavity, the following symptoms may occur:

• inability to breathe deeply, progressing dyspnea,
• malaise,
• persistent dry cough, resulting from irritation of nerve endings located in the pleura,
• as a rule, patients suffering from exudative pleurisy lie on the affected side to make it easier to breathe.

The main causes of this lung cancer complication are metastatic lesions in the chest lymph nodes and pleura. The metastases increase capillary permeability, so, on the one hand, there is more fluid flowing into the interpleural space, and, on the other hand, its outflow through the lymph vessels is impaired.

The condition is diagnosed with the help of X-rays, CT scan, diagnostic puncture or thoracoscopy.

Treatment

If the condition is diagnosed as stage 4, palliative therapy comes to the fore, which can prolong life by reducing the size and slowing the progression of the tumor, as well as relieving pain and improving the patient's general condition. Surgery is only used to remove single distant masses or, in the case of complications that threaten to cause the patient’s rapid death. For example, a stable remission at this stage of cancer can be achieved if there is only one primary tumor in the lung tissue and a single daughter tumor in the periphery (both neoplasms are to be removed surgically, which is combined with of radio- and chemotherapy).

How to prepare. If cancer is detected, no special lifestyle or diet is needed for targeted and immune therapies.

Treatment with cytostatics also affects healthy cells, so one needs to make sure that they replenish protein (with more lean meats, fish, poultry, legumes, dairy products, and eggs if tolerated). It is also necessary to eat sufficient amounts of fruits and vegetables, including those with a high content of vitamin C - sweet peppers, currants and so on. Furthermore, it is advisable to take additional B vitamins, drink enough fluids, including clear water and juices - beet, tomato, lingonberry, raspberry (if platinum-based drugs are prescribed).

Side effects of targeted therapy are nausea, dry skin, vomiting, loss of appetite, diarrhea, fever, cough, skin rashes, and increased fatigue. These usually go away during the treatment, or when it is over.

Immunotherapy

The following types of immunotherapy are used for lung cancer:

Activated T lymphocytes are the cells that are obtained from the patient's venous blood and "trained" to actively fight a specific type of tumor, then injected back into the body.

Therapeutic vaccines help better destroy cancer cells that have settled in the liver, kidneys, and other parts of the body In the advanced stages. In SCL or NSCLC, such vaccines are targeted against MAGE-3 and NY-ESO-1 antigens (detected in 42% and 30% of cases, respectively).

Inhibitors of PD-1 (an immune checkpoint which suppress T-lymphocyte activity of fighting the tumor) can also be used at stages II-IV. These are monoclonal drugs (pembrolizumab, etc.).

Chemotherapy

For many years the core of stage IV lung cancer treatment were platinum-based substances. They increased life expectancy, on average, by 10 months. Cisplatin and other drugs of the same group were effective in about 20-35% of neoplasms. However, platinum drugs themselves have quite a few side effects. These include damage to hematopoietic organs and the kidneys.

Recently other substances (pemetrexed, etc.) have been developed for treatment of advanced stages of NSCLC and SCLC, which are used as monotherapy, as well as in combination with platinum-based medications. In the latter case the platinum-based drugs are tolerated much better.

The most common regimens for SCLC include:

• etoposide with cisplatin or carboplatin,
• irinotecan with cisplatin,
• cyclophosphamide + doxorubicin + vincristine (2nd line drugs).
• topotecan, paclitaxel may also be applied.

Chemotherapy drugs for lung cancer may be given intravenously or orally (as tablets). As a rule, each cycle lasts a few days, followed by a short break. During this time, the body has a chance to recover.

Radiation therapy

In the advanced stages of the disease, it is a supplementary method to fight single metastatic foci. As a rule, distant radiotherapy is administered. It is often given in the end of the basic chemotherapy course.

Prophylactic cranial irradiation is common practice at any SCLC stage following a partial or complete remission of tumor growth. It helps to increase life expectancy. The standard dose is 25-30 Gy.

Treatment of certain metastatic lesions in stage IV lung cancer

The brain. Single foci are removed using stereotactic surgery and gamma knife. Occasionally, conventional surgery may be indicated.

The bones. Systemic chemotherapy is supplemented by administration of bisphosphonates, especially for pain syndrome or fractures.

Other organs with solitary tumors. Along with basic treatment, short courses of radiation therapy may also be considered.

How exudative pleurisy is treated

Pleurocentesis. The procedure consists in the removal of fluid from the interpleural space using a special needle and syringe. Often at the end a drainage tube connected to a special container is placed for further outflow.

Chemotherapy. In almost every second patient with cancer, exudative pleurisy disappears under the basic course of chemotherapy, provided that the tumor proves to be sensitive to these drugs.

Pleurodesis. A drug is injected into the pleural cavity that causes the layers of the pleura to stick together. This prevents future accumulation of fluid.

What affects the life expectancy of stage IV lung cancer patients, how long can they live?

How long a person can survive depends largely on the tumor features, such as its growth rate and tendency to metastasize. There are cancers that grow extremely slowly, so proper treatment can prolong life by years even at stage IV.

However, there are tumors which are characterized by aggressive growth and tendency to metastasize quickly. Their prognosis is less favorable, but novel therapies can bring encouraging results, slowing down the progression of the disease.

The course of cancer may be aggravated by other disorders. For example, decompensated diabetes, severe renal or cardiac failure, blood clots, chronic infections, etc.

Paradoxes of age

Elderly patients are thought to have the worst time with lung carcinoma, as they have less chance of recovery than younger ones. And the reason for this is the limited choice of treatment options due to the greater number of contraindications associated with their chronic conditions. However, each age has its own advantages:

In the young age, there is a wide range of therapies. They are easier to tolerate, the body's resources are better. The problem is in accelerated metabolic processes, which can give rise to early metastasis.

For the elderly not all drugs are suitable, their side effects are observed more frequently. However, metabolic processes are slowed, which can lead to a more indolent course of cancer.

However, today neither the elderly, nor even the senile age is a contraindication for antitumor treatment, since modern medicine has an impressive arsenal of remedies. For example, at stage IV of lung carcinoma, treatment may include:

• chemo-, radio-, hormonal, immune and targeting therapies;
• accompanying treatment - bone strengthening (osteomodifying agents, including bisphosphonates), prevention of chemotherapy complications (such as vomiting, nausea, anemia, etc.)
• cytoreductive surgery (reduction of tumor mass volume);
• local cryodestruction;
• symptomatic care (pain relievers, diet, sedatives).

How can life be prolonged?

Doctors use a whole range of palliative care methods to ensure longer life span. It is important for a person to be able to live as full a life as possible despite the tumor, without suffering.

Participation in clinical trials

For many cancer patients this is a chance to get treatment with novel drugs, which in some cases may successfully keep under control their SCLC or NSCLC for many years. According to their legislation, in most countries any new tumor drug can be registered only after a number of clinical trials, including those on volunteers. And this usually takes several years. Only then the drug appears for sale in pharmacies.

In the case of stage IV malignancies, there is no time to wait for the right drug to become available. It is participation in clinical trials of a new medicine that solves the issue. As a rule, the patient signs an informed consent, which lists all known risks, including that the medication may not be effective. The volunteer agrees to strictly adhere to all protocol terms, to take the medication in a timely manner, and to visit the medical facility specified in the contract for follow-up examinations.

These patients' rights are monitored by an ethics committee (international or state-specific).

What else is important to know about stage IV NSCLC or SCLC.

Symptom management. As a rule, local and general signs of the disease are joined by a variety of complications occurring during the basic course of treatment (chemotherapy, radiotherapy, etc.). Measures to alleviate the disturbing symptoms include:

• detoxification;
• anti-vomiting medications;
• general tonics;
• supportive therapy, aimed at improving chemotherapy tolerance;
• treatment of exudative pleurisy, solitary distant tumors;
• effective pain management;
• support of vital organ and system function.

To reduce vascular injury, chemotherapeutic agents can be injected through a special port-system, which is a reservoir located under the skin and connected to the vein with the help of a catheter. In this case, one does not have to traumatize the vessels at every infusion, since it is enough to insert a needle by piercing the skin and the membrane of the device.

Why doesn't the tumor respond to treatment, or why does metastatic growth resume after a long remission? Cancer cells are cells of the body itself, whose growth and reproduction gets out of its control. And they are adapting to survive under difficult conditions.

Any cancerous node is a cluster of various cancer cells that respond differently to treatment with cytostatics or targeted drugs. It is possible that in a tumor, the first ones to disappear will be those that have proven to be the most sensitive to a particular type of treatment. However, this also contributes to the process of natural selection of cancer cells resistant to any chemotherapy. They survive and subsequently have a weaker reaction to treatment. Thus, after a long remission, metastatic growth may resume.

In addition, some of the cancer cells may fall into a "dormant" condition even for several years, only to suddenly "wake up" and start multiplying and growing.

In any case, you should trust your doctor when they recommend you to undergo another biopsy or to give up the chemotherapy regimen that was successful before. After all, with each new cycle, the tumor gets "smarter," so the previous methods no longer work, and the periods of remission get shorter and shorter. Eventually, there comes a point when the neoplasm becomes incompatible with life.

When known therapies no longer work, an adequate symptomatic therapy can also prolong the life of the patient. This care is usually provided by specially trained nursing staff at a hospice.

Second opinion

An experienced consultant from Germany or another country with an advanced level of healthcare will help:

• to evaluate the current treatment,
• to suggest the most effective options,
• to learn about the cutting-edge therapies.

Getting a second opinion is a worldwide practice, allowing you to minimize medical errors and choose the best treatment strategies. By ordering a consultation on our website, you can get answers to all questions concerning your issue.

References

1. Lesser, T; Doenst, T; Lehmann, T; Mukdessi, J/ A randomized study of a commonly performed video-thoracoscopic procedure// Dtsch Arztebl Int 2019; 116: 329-34. DOI: 10.3238/arztebl.2019.0329
2. Gavin S Jones, David R Baldwin / Recent advances in the management of lung cancer//
3. PMID: 29700092 PMCID: PMC6334032 DOI: 10.7861/clinmedicine.18-2-s41.
4. Sen Yang, Zhe Zhang , Qiming Wang / Emerging therapies for small cell lung cancer// J Hematol Oncol. 2019 May 2;12(1):47. PMID: 31046803 
5. М.М.Бяхова 1, 2, С.Н.Минаков 3, Г.А.Франк / Заболеваемость раком легкого в Московской области (1998–2018) // Пульмонология. 2020; 30 (4): 401–407. 
6. Чубенко В.А., Бычков М.Б., Деньгина Н.В./ практические рекомендации по лекарcтвенному лечению мелкоклеточного рака легкого//© Российское общество клинической онкологии (RUSSCO) 2019 г.