Special Feature:Diseases and Cures

[Part 1] Lung Cancer

For centuries cancer was feared as a disease that inevitably resulted in death. Now, thanks to continuing advances in medical science, cancer can be cured in over 90% of cases provided that it is discovered early. Unfortunately it is still difficult to cure some forms of cancer, or cancer that is diagnosed too late.
Lung cancer is one of the most intractable forms of cancer. In Japan it has the highest mortality rate of any type of cancer, claiming 73,396 lives (52,505 males, 20,891 females) in 2014. Is there no way to halt this disease, which is affecting a growing number of people worldwide? In this article we will look at some of the front-line efforts to fight lung cancer.

Supervising editor: Harubumi Kato, Honorary Director, Niizashiki Central General Hospital, Professor Emeritus, Tokyo Medical University, Professor, International University of Health and Welfare Graduate School Report: JQR editorial staff Illustrations: Mari Kaneko

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Global Increase in Lung Cancer

Lung cancer is one of the most feared diseases. Early diagnosis is difficult, and in many cases the disease has already reached the inoperable stage by the time it is discovered. The statistics are frightening. According to one survey, the five-year survival rate for lung cancer discovered early in stage I is 80%. This falls to 40% in stage II and just 20% in stage III.
Statistics based on cancer locations show that lung cancer has had the highest mortality rate of any cancer location in Japanese males since overtaking stomach cancer in 1993. Colorectal cancer is still the leading cause of cancer mortality in females, but the mortality rate for lung cancer continues to rise. The number of lung cancer patients is increasing steadily and is expected to reach 140,000 by 2020.

Total World Cases Approaching 2 Million

This trend is mirrored in the global statistics. Lung cancer is the leading cause of death among all cancers, and the situation is especially serious in China. According to the World Cancer Report published by the World Health Organization (WHO) in 2014, a total of 1.82 million people developed lung cancer in 2012, with China accounting for 36% (650,000) of new cases. Given that China has only 19% of the world’s population, this figure seems extraordinarily high. It is estimated that almost one million Chinese will be suffering from lung cancer by 2025. WHO attributes China’s serious lung cancer problem to a high smoking rate and air pollution.

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Lung cancer is increasing in every country. Smoking is the most important cause, but environmental deterioration is providing additional impetus.  

Smoking and Air Pollution are Key Causes

With 350 million smokers, China is the world’s biggest consumer of tobacco. The smoking rate for adult males is 53%, and over 70% of Chinese are exposed to second-hand smoke on a daily basis. Smoking is linked to the development of squamous cell and small-cell carcinomas. A smoking index (average number of cigarettes smoked per day times years of smoking) of 400 or higher is a warning sign. Anyone with a smoking index of 600 or higher is at serious risk.
China also has serious air pollution caused by factories and motor vehicles. According to Deputy Section Head Dana Loomis of the International Agency for Research on Cancer (IARC), the problem has worsened dramatically since the late 20th century, and we are now seeing a delayed increase in lung cancer cases due to air pollution, which ranks alongside smoking as a major factor.
Air pollution is a deep-rooted problem, but smoking can be reduced through individual efforts. Experts all say that first step toward avoiding the risk of lung cancer is to stop smoking, and that prevention should begin with the avoidance of passive (second-hand) smoking.

Understanding Lung Cancer

Lung cancer is a generic term for cancerous changes triggered by various factors in parts of the tissues that make up the trachea, bronchi and alveoli of the lungs. As this terrible disease progresses, the cancerous cells proliferate while destroying the surrounding tissues. Cancer cells also disperse through the bloodstream and lymphatic system, eventually leading to the death of the patient.
We talk simplistically about lung cancer, but in fact there are various forms of the disease that vary widely in terms of ease of discovery and treatment. We will learn first about these different types of lung cancer. There are two methods of classification.

Classifying Lung Cancer—1 Classification by Location

Lung cancer is divided into central lung cancer, which develops in the large bronchi, and peripheral lung cancer, which occurs near the pulmonary alveoli in the depths of the lung. Central lung cancer is difficult to detect using x-rays because the bronchi are hidden behind the heart, so this type of cancer often remains undiscovered until a cytodiagnosis is performed following the appearance of symptoms. Peripheral lung cancer forms in the depths of the lungs and progresses without causing symptoms. It is usually discovered as a result of chest X-rays or CT scans.

Classifying Lung Cancer—2 Classification by Tissue Type

Different types of cancer also become apparent when cancerous cells or tissues obtained through biopsies or surgeries are examined under a microscope. Based on these differences, cancers can be classified into small-cell and non-small-cell carcinomas. Small-cell carcinomas are further divided into small-cell and combined small-cell carcinomas. There are three sub-types of non-small-cell carcinomas: adenocarcinomas, squamous cell carcinomas and large-cell carcinomas. Squamous cell carcinomas and small-cell carcinomas are classified as central lung cancers, while adenocarcinomas and large-cell carcinomas are commonly classified as peripheral lung cancers.
Around 60% of lung cancers are adenocarcinomas. The next most common type is squamous cell carcinomas. The incidence of small-cell and large-cell carcinomas is relatively low. In Japan and other advanced countries, a decline in smoking has been accompanied by a downturn in the incidence of central lung cancer. However, the incidence of peripheral lung cancer is rising.

Main Symptoms of Lung Cancer

A person with lung cancer will exhibit respiratory symptoms, such as coughing and sputum. These symptoms, and sometimes bloody sputum, are seen in central lung cancer cases from an early stage. While these symptoms are similar to those caused by cold, there will be no runny nose or fever. Anyone suffering from a prolonged cough or sputum should see a doctor as soon as possible.
A frightening characteristic of peripheral lung cancer is the fact that it progresses without producing any symptoms. By the time subjective symptoms appear, the disease has often advanced to an inoperable stage. That is why people are so afraid of lung cancer.

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Basic Facts about Early Detection

With lung cancer, detection and appropriate treatment at an early stage are vital. However, there is no global standard defining the progression of the disease in the early stage. For example, the United States and Japan each have different definitions. The Japanese definition, which is more rigorous, stipulates that the “early stage” of central lung cancer is the stage at which the cancer is still confined to the bronchial walls and has not metastasized to the lymph nodes and remote sites. Early stage peripheral cancer is defined as the stage at which the carcinoma is no more than 2 cm in diameter and has not metastasized to the lymph nodes and remote sites.

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Regular Check-ups

Ideally anyone aged over 40 should have a regular check-up. In particular, anyone who meets the conditions listed in the above table should be aware that they have a high risk of developing lung cancer and should actively undergo testing. The accepted method for lung cancer testing is chest X-rays for those aged 40 and older, and sputum cytodiagnosis for smokers aged 50 and older, and anyone with a smoking index over 400. However, a problem with chest X-rays is the large number of blind spots. Carcinomas are small and may be obscured by bones, arteries, the heart, the diaphragm or other structures.
An effective way to detect these hidden cancers is a computerized tomography (CT) scan. With a CT scan, X-rays are beamed into the chest from multiple angles, and the images are analyzed by a computer. This produces clear cross-sectional images of the lungs, allowing the discovery of quite small carcinomas and low-contrast lesions. The detection rate is about 10 times higher than with chest X-rays, allowing cancers to be discovered at earlier stage.
The drawbacks are cost and radiation exposure. A CT scan exposes the chest to 100 times more radiation than a chest X-ray. With a low-intensity CT system, the exposure can be reduced by a factor of 10. Many medical institutions already have these systems, but it’s best to check first. Heavy smokers should have a CT scan every year, but once every 2-3 years should be ample for non-smokers and people who have not smoked for at least 15 years.

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Basic Facts about Treatment

Effectively Combining the Three Pillars of Cancer Therapy

As stated earlier in this article, lung cancer is a serious form of cancer with a five-year survival rate of just 20% for stage III sufferers. Since the symptoms of the disease are similar to those of the common cold, they are often overlooked.
If lung cancer is detected in stage I, the standard surgical approach is the removal of one of the lung lobes, of which there are five. This is known as a “lobectomy.” With stage II and later lung cancers, surgery is combined with chemotherapy and radiotherapy, which are the other main forms of treatment. Molecularly targeted drugs can be effective if the cancer has advanced even further. These are also useful in cases of adenocarcinoma, which has become increasingly common in recent years. Severe side effects were a problem with these drugs, but efforts are now being made to improve administration regimes.
Lung cancer is difficult to cure. However, treatment methods continue to improve steadily. The aim is to achieve a full cure by selecting the best methods and using them to their full potential.

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Photodynamic Therapy (PDT)

With this method, a laser is used to eradicate cancer cells. In early-stage central lung cancer cases, over 90% of patients can expect to achieve a full recovery. Even if PDT itself does not fully cure the cancer, there is a high probability of full recovery if it is combined with other methods, such as radiotherapy and surgery. (Please see the article about Dr. Kato in this issue of JQR on page 34 of this issue.)

Endoscopic Surgery

The surgeon removes lesions by using a thoracoscope (chest endoscope) inserted through small incision in the patient’s chest to control instruments inserted via another incision. Post-surgery recovery is quicker, since the physical impact on the patient is minimal compared with open chest surgery. In recent years, laparoscopic procedures have started to overtake the open chest approach as the main surgical method.

Robotic Surgical Assistants

The da Vinci Surgical System inserts robotic arms into four small holes drilled into the patient’s armpits. With this system, the surgeon carries out the procedure by remote control while observing 3D images of the interior of the patient’s chest. Delicate procedures can be performed, since the robotic arms have greater freedom of movement than human hands. Compared with open chest surgery, the physical damage to the patient is extremely small, and recovery is fast.

Intraoperative Navigation

Computerized tomography (CT) scans provide information about diseased areas in the form of 3D images to guide the surgeon to the exact locations where excision is required. This cutting-edge technology is used to support endoscopic surgery and robot-assisted surgery. It provides detailed images of blood vessels, which are different in every patient, and is also useful for the planning and rehearsal of surgeries.

Proton Beam and Heavy Particle Beam Therapy

These are both forms of radiotherapy. Since these technologies allow intense radiation to be concentrated only on the cancer lesion, the physical impact on the patient is reduced, and there are fewer side effects. As a general rule these methods are used on single cancer lesions that have not metastasized. Heavy particle beams accelerate protons, which are the nuclei of hydrogen atoms.

Molecular-Targeted Therapy

This approach employs a different mechanism from conventional anti-cancer drugs, which are highly toxic, and only specific molecules (cancer cells) are targeted. A key feature of molecular-targeted therapy is the small amount of damage to healthy tissue, compared with conventional chemotherapy. In addition, this method can be administered on an outpatient basis without the need for hospitalization. However, these drugs do not cure cancer.

Immunotherapy (Immune Cell Therapy)

This therapy works by increasing the immune cells and enhancing the immune system. When used in combination with the three major therapy methods, it has the potential to produce synergistic benefits and mitigate side effects. Immunotherapy methods include highly-activated NK cell therapy, T-LAK therapy, CTL therapy and dendritic cell therapy.

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