Lung Cancer — Stages, Diagnostics and Treatment

Symptoms of lung cancer depend on the anatomical location of the neoplasm and the nature of its growth in the bronchus, so the peripheral tumor manifests symptoms later than the central one.

Different Cancer Forms Characteristic Features

Today, both variants of lung cancer — central and peripheral — are detected almost equally, which is facilitated by the multiply high resolution capabilities of CT in comparison with classical radiography of the chest organs.

In men, the central localization of the tumor predominates, whereas in women the peripheral forms prevail a little. The right lung is affected more often than the left.

Squamous cell carcinoma progresses slower than adenocarcinoma, which is detected earlier due to the rapid formation of metastases, especially on the pleura. The squamous structure in men occurs 6 times more often than adenocarcinoma; and with age, the frequency of glandular formation also decreases, after 60 years of age it is hardly 5–6%. Women, on the contrary, have glandular cancers four times more often.

Small-cell and undifferentiated variants of the tumor are booming and very early appear metastases, the clinical signs of the disease cover the patient with a wave and in all its diversity.

Early-onset Lung Cancer Symptoms

The trouble of the disease is the sufficient compensatory capacity of the organ, when switching off part of the lobe from the breath passes subtlety, unless inflammation occurs. If inflammation of the lungs in a mature man with a long smoking history is treated without an X-ray examination, it may take several more months to detect the cancer site.

When a large bronchus tumor is blocked, a dry hacking cough appears that does not respond to antitussives. Most patients are smokers with clinical manifestations of COPD, a chronic obstructive disease that was formerly called smoker’s bronchitis. With COPD, regular morning cough with sputum and shortness of breath is the norm of life, in the cold season these symptoms worsen. In cancer, the cough only increases with time, sputum is not necessary.

Widespread Disease Symptoms

Dyspnea is not a pathognomonic symptom for an oncologic process, it is more often accompanied by COPD and heart disease. When the tumor is blocked by the lumen of the large bronchus, it occurs with concomitant inflammation in the zone of low airiness. But in most cases, marked dyspnea develops with metastatic pleurisy or metastases in the lungs or lymph nodes in the mediastinum. Peripheral tumor will cause a feeling of lack of air in case of growth of the tissues of the chest wall and a violation of this respiratory excursions of the chest.

Pain as a symptom of the disease occurs when the pleura and chest structures are involved in the tumor process. Severe pain may accompany accompanying inflammation, but antibacterial therapy quickly relieves it. The pain caused by the growth of intercostal nerves, or metastases to the ribs and spine is stopped only by special therapeutic measures.

Hemoptysis is a symptom of a far-gone process, it can be in the form of streaks in sputum, intensely colored spitting and even bleeding, it is a symptom of disintegration inside the tumor and corroded by the vessel wall cancer.

Most of these symptoms and even a combination of symptoms can occur in any other pathological condition of the lungs and even extrapulmonary disease.

When a neoplasm is localized in the apex of the lung and nerve germination of the brachial plexus, eye symptoms develop: a visual reduction of the eye on the side of the cancer nodule, the omission of the upper eyelid and a change in the pupil. These symptoms are accompanied by pain in the neck and shoulder and a violation of the mobility of the arm — hanging like a whip.

Symptoms of Non-cancerous Organs and Systems

Such symptoms are called paraneoplastic, that is, occurring in the presence of cancer, but are not associated with tumor damage. In lung cancer, the tumor can produce active substances and hormones, causing specific manifestations. After removal of the diseased lung, all symptoms disappear.

Most often there are pains in the bones, their structure changes, the nail phalanges of the fingers thicken, large joints swell. Possible skin manifestations of different types, increased blood clotting with the formation of blood clots, high pressure surges and neurological manifestations.

Very often, such paraneoplastic manifestations are accepted for metastases and the patient is denied radical surgical treatment, specialists of the Clinic Medicine 24/7 with the help of high-precision equipment will perform differential diagnostics and remove from the diagnosis what should not be there, which will expand the possibilities of therapy and the patient’s prospects. Sign up for a consultation: +7 (495) 151-14-47

The causes of lung cancer have been actively studied since the early 1950s, but finally and unconditionally determined only such a risk factor as smoking and exposure to harmful substances in their professional activities, all other factors involved in the initiation of a tumor have a shaky scientific background.
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Lung cancer is associated with socioeconomic status, especially in the male population, smoking and professional contact with carcinogens and toxic substances, unbalanced nutrition, and poor lung system health.

All causes can be divided into two major groups: genetic and various risk factors. They are considered to be changeable, because the person chooses them himself, and if they cease to influence them, the risk of illness decreases, such as smoking, occupational hazards and environmental pollution.

Most studies have confirmed the role of heredity in the development of glandular cancers, whereas variable factors cause a squamous and small cell variant of the tumor. Of course, such a correlation is not always observed, but often.

There is no complete clarity about the effect of nutrition: alcohol, in particular beer, increases one and a half times, whereas fruits and vegetables consumption reduces the risk by half.

Most Frequent Lung Adenocarcinoma Causes

In recent decades, the proportion of glandular forms has increased in the structure of lung cancer, while the small cell tumor, on the contrary, has decreased.

At the end of the last century, an increase in the incidence of women, including non-smokers, began to be noted, the primary morphological form — adenocarcinoma and its subspecies with localization in the peripheral parts of the organ — bronchioalveolar carcinoma (BAR). The reason is seen in inadequate production of estrogen, which was confirmed by the discovery of sex hormone receptors on the surface of lung cancer cells.

Heredity plays a role in the development of glandular forms, it is noted that the probability of getting sick from close relatives of a patient with lung cancer is increased threefold. Hereditary malignant tumor occurs at a young age and adenocarcinomas prevail. It is assumed that genetically transmitted inability to detoxify carcinogens and a decrease in the activity of certain enzymes involved in their metabolism. It is necessary to think about the hereditary type of cancer when the disease was observed in the family of three close relatives.

Glandular neoplasms often develop in the rumen, so there are so many cancer patients among tuberculosis patients. Half of those who have recovered from tuberculosis will sooner or later fall ill with lung cancer, again different variants of adenocarcinoma will prevail.

The effect of immune suppression on morbidity is confirmed by the frequent development of a pulmonary tumor in lymphoproliferative diseases and hereditary syndromes.

Autoimmune scleroderma is combined with glandular cancers.

Predominant causes of squamous and small cell lung cancer

In the middle of the last century, scientific evidence of the influence of smoking on the development of a malignant neoplasm was found, the probability increased with an increase in the duration of smoking and the number of cigarettes smoked, the quality of tobacco. The transition of Russians to better quality tobacco in the 90s already by the second decade of the current century led to a decrease in the incidence, because Soviet dark tobacco for the respiratory organs is worse than light varieties.

Active government opposition to the spread of smoking led to a decrease in the incidence of the small-cell form of the disease, which was associated with aggressive smoking — several packs per day. The risk begins to decrease only after 5 years after giving up the habit, and with continued tobacco worship, the risk increases 4 times faster than the duration of smoking, the longer, the greater the likelihood.
Passive smoking — inhaling the smoke of other people’s cigarettes also increases the cancer risk by 70%. With the same number of cigarettes and the duration of smoking, women’s risk is always higher than men’s due to greater sensitivity to carcinogens.

Metabolism of smoking products is different in different nations, therefore the probability of becoming a cancer patient in Indians, Japanese and Latin Americans is lower, but higher among African Americans and whites.

Carcinogens of burning fuel and waste from industrial enterprises, urbanization are unfavorable due to air pollution, they add 10 cases of disease every year for every 100 thousand inhabitants.

Work in the steel industry, especially nickel and copper smelting, a decade of working with asbestos doubles the risk of cancer, 30 years of work — the likelihood is exacerbated six times. Uranium mines cause small-cell tumor, this option was noted in the victims of the atomic bombings of Hiroshima and Nagasaki.

Emphysema and COPD — background for small cell and squamous cell carcinoma. However, even a smoker may have a BAR, and a smoker who has never smoked may have a squamous cell tumor. At the Clinic Medicine 24/7, they will conduct an examination for the minimum time and find out everything about the disease in order to start the best treatment soon. Sign up for a consultation: +7 (495) 151-14-47

Causes and Risk Factors

In the overwhelming majority of the disease arises due to the long-term inhalation of mucosal light toxic substances, primarily the carcinogenic components of tobacco smoke, which additionally burns the respiratory tract, supporting sluggish chronic inflammation in them.

In smokers, the likelihood of developing lung cancer increases in parallel with the years of smoking and the number of cigarettes smoked per day — the longer and more the number, the sooner the tumor will develop. Non-smokers also develop pulmonary carcinoma, which today is associated with passive smoking. All this is true for the squamous variant; with adenocarcinoma, the correlation is not so obvious.

Proven connection of the disease with a genetic predisposition, especially in women affected by adenocarcinoma and never smoked with Asian genes. Genes not only indulge in malignant degeneration, but are also able to protect against cancer, which is recognized by the example of extremely aggressive smoking long-livers without any signs of smoking-related diseases, although their cohort is extremely small.

Radon radiation also undermines lung health, by the way, according to American experts, this is the most frequent risk factor for lung cancer after tobacco smoke. Employees of «harmful» enterprises, where asbestos and arsenic are used in the industrial cycle, are more prone to illness. Risk factors for oncologists include the adverse effects of radiotherapy for another disease.

Lung Cancer Symptoms

High mortality from lung cancer, primarily due to late diagnosis, because in most cases, the obvious signs of the disease occur too late, especially when the tumor is localized far from the large bronchi.

Often, peripheral cancer is manifested only by complications of the tumor — symptoms of pneumonia with intoxication due to a ventilation failure of a large area or bleeding due to the destruction of part of the neoplasm.

Symptoms of oncopathology do not differ from any other pulmonary process, their duration and persistence with respect to drug therapy should be alarming. Most smokers are chronically coughing with difficult sputum, shortness of breath, similar symptoms occur when a large bronchus carcinoma is blocked.

Pathognomonic malignant process of hemoptysis, characteristic of advanced tuberculosis, all clinical manifestations are very similar. Since the blood in the sputum appears at stage 3–4 with the internal disintegration of a large tumor site, debilitating weakness and temperature jumps accompany this process.

Dyspnea occurs when a large part of the lung is turned off from gas exchange, which occurs when a large bronchus is blocked or airways conglomerate with conglomerates of metastatic lymph nodes in the mediastinum. Progressive dyspnea is characteristic of metastatic lesions of pleural sheets with the development of pathological fluid — pleurisy. Pain refers to late symptoms, and is often associated with germination of the chest wall cancer or involvement of the pleura in the tumor. If the apex of the lung is affected, the pain is particularly intense because the carcinoma damages the large nerve trunks.

Some cancer cells are able to synthesize hormone-like substances that trigger the symptoms of endocrine pathology, severe joint pain, muscle weakness and extensive skin lesions. Already on the first day after the operation, no trace remains of paraneoplastic manifestations.

With a small neoplasm, the symptoms of the malignant process are absent, therefore, if there are risk factors for the disease, it is necessary to be regularly examined to catch the disease in the operable stage. Fluorography and X-ray examination will not help, need CT. We will help you determine the optimal timing of the survey.

If you detect suspicious symptoms, consult a doctor immediately.

Lung Cancer Types

According to the cell structure, the whole lung cancer is divided into two types: non-small cell, which more than two-thirds of patients are ill, and small cell.

The largest group, which accounts for three quarters of the disease — non-small cell lung cancer (NSCLC), and make up its adenocarcinoma, squamous and large cell tumors. The course and prognosis of tumors of different cell structure varies, but the general principles of the therapeutic strategy are the same, where the main path to salvation is surgery, supplemented by radiation and drug therapy: targeted, immune and cytostatic chemotherapy.

By location, the central, growing in the large bronchi, and the peripheral — the lesion of the smallest and smallest bronchi or pulmonary sacs — alveoli — are distinguished.

Central can grow:

• inside the bronchus — exophytic or endobronchial;
• from the bronchus out into the lung tissue — endophytic or exobronchial;
• a muffler enveloping the bronchus outside — peribronchial;
• mixed.

When peripheral fundamentally distinguished:

• nodal type of growth;
  
• pneumonia-like variant is very similar to the radiological picture of inflammation;
• Pancoast tumor with localization at the apex of the lung.

The choice of treatment is based on the morphological classification; in the planning of the operation and the radiation fields, surgeons and radiologists use the clinical-anatomical classification.

In the treatment of non-small cell lung cancer, serious changes have occurred with a focus on the selection of individual therapy for the presence of certain genes in the tumor. In order to control the behavior of a neoplasm in the course of therapy, the identification of tumor markers and the control of their changes are being increasingly used. Treatment of small cell lung cancer has not yet experienced revolutionary changes, systemic chemotherapy is still in progress, to which radiation is sometimes connected, and very rarely — surgery.

Small cell carcinoma (MRL) is also represented by several cellular variants combined into one group by the high aggressiveness they manifest and a pronounced sensitivity to cytostatics — chemotherapy.

Diagnostics

With all the love of the Russian Ministry of Health towards fluorography and radiography of the chest, only computed tomography (CT) allows time to identify the disease and monitor its response to treatment.

Mandatory examination before the start of treatment — bronchoscopy, in which the trachea and bronchi are examined, a biopsy is taken from suspicious areas. Without knowledge of the exact cellular structure of the tumor, it is impossible to prescribe adequate treatment.

Sometimes, in case of peripheral formation or suspected metastasis, it becomes necessary to examine the pleural covering of the lung, for which endoscopic equipment is used, and the examination process itself is called video-assisted thoracoscopy.

What Tumor Markers Tell About the Disease?

Tumor markers do not allow detection of lung cancer in a «blank spot», for example, when testing blood for prophylactic examinations, as they increase in other benign chronic and acute processes, in pregnancy and even excessive use of certain products on the eve of the test.

Tumor markers in difficult diagnostic cases will help to distinguish a benign lung process from cancer, as well as more accurately track the changes in the neoplasm during treatment.

What markers can increase with different cellular structure:

• Cancer embryonic antigen (CEA) — for all types;
• Neurospecific enolase (NSE) — SCLC;
• Squamous cell carcinoma marker (SCC) — squamous, large cell;
• Cytokeratin fragment (CYFRA 21–1) — for all variants of NSCLC;
• Cancer or carbohydrate antigen 125 (CA-125) — adenocarcinoma.

What Genetic Analyses Should be Done

All malignant pulmonary tumors must undergo genetic research, there are several options to choose from: immunohistochemical analysis (IHC), polymerase chain reaction (PCR) or cytogenetic research (FISH). Genetic analysis needs to be done by everyone, even with an operable and small process, in the future this information may be required for the selection of treatment for metastasis.

In cancer cells, EGFR gene mutations are sought in two DNA regions — exon 19 and exon 21, and a mutation in the form of transfer to the wrong place in the ALK and ROSI genes. If there are no mutations, then a test for the synthesis of PD-LI protein by cancer cells is performed.

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Lung Cancer Stages

Lung cancer in the early stages of Russians diagnosed to the insult is rare:

• Stage 1 — 13%
• 2 tbsp. — 16% every third patient for treatment comes with a process of local neglect
• Stage 4 is detected in 41% of cases.

Staging of the neoplasm of the thoracic cavity is rather difficult, since it includes special variations for peripheral carcinoma and central cancer, besides a large number of intrathoracic lymph nodes groupings and involvement in the pleura process are taken into account. Each stage corresponds to a certain size of the tumor and a group of metastatic lymph nodes, and inside the stage it is assumed to be divided into A and B.

In a strongly abbreviated version, the gradation is as follows:

• 1 tbsp. — A tumor up to 5 centimeters or in the main bronchus, but without signs of metastasis anywhere;
• 2 tbsp. — node up to 7 cm with a lesion of the lymph nodes of the root, or without metastases with a large amount of neoplasm;
• 3 tbsp. — any volume of cancer conglomerate in the lung and the defeat of metastases of mediastinal lymph nodes;
• 4 tbsp. — the process in the lung tissue is not important, because there are already metastases in other organs or in the opposite lung, pleura. For more informative, the diagnosis «lung cancer 4 stages» is supplemented with a Latin abbreviation of metastasis localization, for example, liver — HEP, pleura — PLE.

The exact establishment of stage 1 opens up the opportunity for the patient to undergo high-tech surgical treatment with minimally damaging endoscopic access and anatomically oriented resection of the patient site. Inadequate staging leads to a vain exploratory operation, when surgery begins with penetration into the chest cavity and immediately ends with inspection and «suturing».

Lung Cancer Treatment

Chemotherapy

Preventive chemotherapy helps protect against recurrence and metastases, so it is performed after surgery, even at stage 1, when there was a node measuring up to 5 centimeters or a lesion of the main bronchus. Chemotherapy treatment begins no later than 8 weeks with sufficient recovery after surgery. For the result, 4 courses are required with platinum preparations.

If there is any doubt about the possibility of performing the operation, the treatment of non-small cell lung cancer begins with 2 courses of preoperative — neoadjuvant chemotherapy, 3 weeks after the last cytostatic injection, an operation can be performed.

In an inoperable process, chemotherapy is combined with radiation or both methods are applied sequentially, this option is less effective, but is better tolerated. In most cases, they are limited to 6 courses of chemotherapy, then the observation and resumption of chemotherapy for the progression of the disease.

The metastatic stage is subject exclusively to drug therapy, the range of active cytostatics is wide, they are complemented by targeted and immuno-oncological drugs. Small cell cancer in only stage 1 is operated, all others are treated with chemotherapy and radiation.

It is especially difficult for chemotherapists to treat patients who have received a full course of radiation. In the Medicine 24/7 clinic, there are exclusive developments that remove most of the clinical problems.

Thoracic Surgery for Lung Cancer

A surgery in the small cell process is rather an exception, therefore, below we will discuss all non-small cell variants: adenocarcinoma, squamous and large cell types.

Only an operation allows healing, but at the time of a malignant process detection, radical intervention is possible in every fifth patient, therefore about 20% of all those treated undergo the five-year period.
Surgical preference is given to the complete removal of a lung — pneumonectomy or removal of a lobe — lobectomy, and in the right triple-lobed lung two lobes are removed — bilobectomy.

If the patient is not in a good condition due to concomitant chronic diseases, excision with the surrounding healthy tissue of a peripherally located cancer node not more than one and a half centimeters in diameter is practiced — this is a resection, which, when coinciding with the anatomical sections of the organ, is called segmentectomy, and in all other cases is referred to as sublobar resection. The latter option of non-anatomical removal somewhat spoils the results with a slightly more frequent recurrence of the process and worse tolerance of the intervention.

Today, with the initial process and a small amount of intervention, the intervention is performed using endoscopic equipment — thoracoscopically with a small incision in the chest wall, which does not impair long-term results, but contributes to early patient recovery with fewer complications.

It is mandatory during surgery to remove lymph nodes in the mediastinum, as well as all lymph nodes that receive lymph from the trachea and esophagus.

Treatment Methods Depending on a Disease Stage

• At stage 1, an operation is performed, if a tumor is detected more than 4 cm involving a pleural sheet, with high aggressiveness potential — stage IB, then preventive chemotherapy is additionally performed;
• In stage 2, in most cases, surgery is possible with mandatory 4 courses of adjuvant chemotherapy;
• At 3 A stage of lung cancer, large-scale surgery is possible with prophylactic chemotherapy, in some cases 2 courses of preoperative chemotherapy with surgery in 3–4 weeks and 2 courses after surgery will be offered;
• Stage 3B excludes surgical treatment, therefore radiation and chemotherapy are carried out, with good health, both methods of antitumor effects are carried out in parallel, and in debilitated patients — consistently;
• Stage 4 lung cancer with metastases to other organs involves only medicinal effects, and the choice of the drug due to the genetic characteristics of cancer.

Targeted Therapy

In the presence of gene mutations, the patient with an inoperable or metastatic tumor is assigned targeted or molecular-directed drugs. Targeted agents are not used for prophylactic treatment — only chemotherapy.

Mutation of the EGFR gene in 19 or 21 exons is the reason for the appointment of blockers of the cellular enzyme tyrosine kinase.

When the ALK / ROS1 gene mutates, tablet form preparations are selected.

If chemotherapy was started for a patient without waiting for a result on tumor genetics, 4 courses of chemotherapy are performed as standard and only after that the targeted effect begins. The cessation of molecular-directed effects is possible only with the resumption of tumor growth or the appearance of new metastases, that is, with the progression of the disease.

With the progression of the process in the next therapeutic line, targeted results showed good results, but not with a squamous variant, for which cytostatic chemotherapy is chosen.

Lung Cancer Immunotherapy

Immunotherapy every 3 weeks is prescribed in the absence of the above-mentioned genetic mutations and when a specific protein PD-L1 d is produced by cancer cells, optimally at least half of the tumor cells.

Immunopreparations are actually the same targeted drugs — monoclonal antibodies, but their place of influence is on the immune cell — T-lymphocyte, therefore this treatment is onco-immunological. With the progression on the background of immunotherapy, another drug is selected, for its purpose analysis for protein expression is no longer required.
Immunotherapy can cause changes in the reaction of lymphocytes to their own tissues, which will manifest itself in allergic processes of an autoimmune nature.

All anticancer drugs, not only chemotherapeutic cytostatics, but also targeted and immunotherapy can cause adverse reactions of varying intensity, sometimes forcing to change the treatment regimen. For a good result, it is very important to administer all the drugs on time and in sufficient doses. Masterfully owning a specialty, the chemotherapists of the clinic will offer effective programs to overcome toxicity and speedy recovery.

Lung Cancer Prognosis

Without surgery, the treatment of lung carcinoma cannot be considered successful, despite serious advances in drug therapy. The majority of patients in the first five years of life after surgery face distant metastases, so brain metastases develop in every third person with adenocarcinoma.

When a disease is detected in stage 1, the survival rate is higher than at stage 3, but even «inside» 1 not everything goes smoothly: 1A promises six out of ten to live more than 5 years, and at 1B only four can. The influence of the morphological structure of the tumor has been observed — with squamous cells, they live longer and survive longer — about 80% of stage 1 than with adenocarcinoma.

• At stage 2, the five-year survival rate is about 35% at 2A and 25% at 2B.
• With 3A, only every seventh, and at 3B — every 20th will be able to forget about lung cancer and live to old age.
• At stage 4, the units survive 3 years after the cancer has been detected.
• Regardless of the initial prevalence in squamous cell carcinoma, 3–4 patients experience more than 5 years, with adenocarcinoma 2–3 out of ten.

The text is based on NCCN (National Common Cancer Network) materials.