In German-speaking countries, lung cancer is the third most common malignant tumour in women and the second most common in men.
The peak incidence is between 68 and 70 years of age. Every year, around 21,000 women and 36,000 men are newly diagnosed with lung cancer in Germany

Lung cancer is primarily caused by harmful substances (e.g. ionising radiation, particulate matter, diesel engine exhaust fumes, asbestos, quartz dust) that enter the lungs with the air we breathe, whereby smoking (including passive smoking!) must be mentioned first and foremost.

Patients who have already had lung cancer or have first-degree relatives with lung cancer have an increased risk of lung cancer (genetically determined).

Lung cancer is recognised as an occupational disease in Germany in cases of occupational exposure to arsenic, beryllium, cadmium, chromium, raw coking plant gases, nickel, polycyclic aromatic hydrocarbons (PAHs), silicon dioxide [7] and passive smoking. However, the risk of developing occupational lung cancer is significantly lower than from smoking.

The risk of developing lung cancer is also increased in the case of chronic lung infections with scarring and pulmonary fibrosis.

Years of worldwide research have proven that nicotine consumption is a major cause of lung cancer. However, smoking has also been linked to the development of pancreatic cancer, bladder cancer, kidney cancer and leukaemia. The risk of developing lung cancer increases with the number of cigarettes smoked per day. The risk of developing lung cancer is higher for women smokers than for men smokers. Quitting smoking can reduce the risk of cancer by 60% after 5 years and by as much as 90% after 15-20 years.

However, passive inhalation of cigarette smoke must also be categorised as hazardous to health and increases the risk of developing lung cancer by a factor of two.

Quitting smoking, even if you already have lung cancer, can be beneficial for the effectiveness of treatment and possibly for survival.

In the early stages, lung carcinoma unfortunately does not cause any typical symptoms and is often only discovered by chance. However, if you experience the following symptoms, you should urgently consult a doctor to clarify the cause:

• Cough, especially if you have had a smoker's cough for a long time and it suddenly changes
• Bronchitis and pneumonia that does not improve despite antibiotics
• shortness of breath
• Chest pain
• General fatigue and severe weight loss
• haemoptysis
• Paralysis or severe pain
• Long-lasting hoarseness

As with all other types of tumour, the same applies here: The earlier the tumour is detected, the greater the chances of recovery.

In addition to a physical examination and laboratory analyses, the following examination procedures are routinely used to diagnose lung cancer: X-ray examinations, in particular computed tomography (CT), bronchoscopy, positron emission tomography in combination with CT (PET/CT) or MRI (PET/MRI) to visualise malignant foci throughout the body and magnetic resonance imaging (MRI).

Medical history and physical examination

During a detailed consultation, the doctor will be informed of all complaints, occupational exposure to harmful substances, smoking habits and previous illnesses (including family history of illnesses). This is followed by a thorough physical examination.

Computer tomography (CT)

Computed tomography is a painless, special X-ray examination (with contrast medium) that scans the body layer by layer and can therefore show the exact location and size of the tumour. The exact spread of the tumour and any metastases, e.g. in the liver, lungs, lymph nodes, bones or adrenal glands, can thus be determined.

Bronchoscopy of the bronchi (bronchoscopy)

During a bronchoscopy, the patient is given a light anaesthetic. The doctor carefully inserts a flexible tube (bronchoscope) with a mini camera at the tip through the mouth into the bronchi. The doctor can now examine the mucous membrane of the bronchial tubes and take tissue samples (biopsies) at the same time. By using a special bronchoscope with an integrated ultrasound probe (EBUS bronchoscopy), the doctor can specifically locate suspected cancerous structures in the area of the bronchi and lymph nodes and take tissue samples. In the case of larger tumours in the airways, for example, these can be removed using the flexible cold probe ("cryoprobe"). If the tumour has caused a narrowing, the airway can be kept free with a stent (placeholder, tube), for example. In this case, it may be necessary to insert a rigid tube instead of a flexible bronchoscope in order to carry out the necessary interventions.

Positron emission tomography in combination with computer tomography (PET/CT) or magnetic resonance imaging (PET/MRI)

The PET scan is an examination in which radioactively labelled glucose (injected into the bloodstream) is used to measure metabolic activity, which is usually increased in malignant tumours, using a special camera. As a result, even tumours or metastases smaller than 1 cm can often be visualised throughout the body. PET examinations are now carried out in conjunction with computer tomography (PET/CT) or magnetic resonance imaging (PET/MRI), which further expands the possibilities of this procedure.

Magnetic resonance imaging (MRI)

MRI is not an X-ray examination, but is based on magnetic field effects. Due to the high image resolution, it is also possible to visualise small structures. In the case of lung carcinoma, MRI is mainly used to examine metastases in the brain.

Sonography (ultrasound examination)

Sonography is a painless and radiation-free examination for the detection of metastases. In principle, the spread of the tumour to other organs or existing metastases (tumour metastases), e.g. in the liver, can be detected.

Skeletal scintigraphy (bone scintigraphy)

By administering a small amount of radioactive substance into the bloodstream, tumour metastases in the bones can be visualised. A special camera recognises the radioactively enriched areas in the diseased bone. This is a gentle examination in which the radiation decays quickly.

Biopsies (tissue samples)

In order to be able to initiate an individually tailored therapy, it is necessary to obtain a tissue sample of the tumour in the lung and/or the metastases already present. This can be done by lung endoscopy or by CT or sonographically guided puncture of the relevant tumours and/or metastases. In individual cases, it is also possible to obtain a sample surgically if this is not possible using other methods.

The staging of bronchial carcinoma is based on the TNM classification.

It describes the spread of the tumour and is the basis for determining further treatment.

T (tumour) stands for the size and extent of the primary tumour, N (node) stands for the number of affected lymph nodes and M (metastasis) stands for the occurrence and localisation of distant metastases (tumour metastases).

Lung carcinoma is a prime example of the development of modern oncology. Until recently, tumours were only divided into 2 groups (small cell and non-small cell lung carcinomas).
Today, tumours are divided into numerous different groups, which also have different treatment concepts.

The prognosis and treatment methods are determined by the tumour stage, the genotype of the tumour, the histology, the age and the concomitant diseases.

The earlier a lung carcinoma is detected, the more favourable the prognosis for the patient. Extensive scientific research has led to the development of internationally recognised treatment guidelines for lung cancer. In recent years, treatment options have developed rapidly, so that the guidelines are frequently adapted.

Therapy goals

Fortunately, the treatment of lung cancer has made great progress in recent years. Step by step, we are approaching the goal of turning lung cancer into a chronic disease that enables long survival with a good quality of life. In principle, a distinction is still made today between "curative therapy" and "palliative therapy", although the boundaries are increasingly blurring.

• Curative therapy:
  If therapy can be carried out with the aim of achieving a permanent cure, this is referred to as "curative therapy". This is possible for lung cancer in tumour stages without distant metastases and without evidence of tumour cells in lymph nodes on the opposite side, if intensive treatment can be carried out.
• Palliative therapy:
  If a tumour has already formed distant metastases, cure is no longer a primary therapeutic goal. This is referred to as "palliative therapy". The goals of palliative therapy must be determined on a case-by-case basis; common goals include prolonging life with minimal impairment of quality of life(palliative life-prolonging therapy) and avoiding or alleviating distressing symptoms(palliative symptom-orientated therapy).

Treatment of small cell lung carcinoma (approx. 15% of lung carcinomas)

SCLC is a very fast-growing, aggressive tumour that forms metastases early on. Surgery or radiotherapy alone without chemotherapy is therefore rarely appropriate for this disease.

Small cell lung carcinomas are categorised into

• Limited disease, i.e. the tumour only grows on one side of the chest cavity, the chest wall is not directly affected and only certain lymph nodes are involved.
• Advanced stage (extensive disease), i.e. any extension of the tumour beyond the definition of limited disease, usually with involvement of other organs (metastases)

Chemotherapy in combination with immunotherapy

The cancer cells of small cell lung carcinoma react particularly sensitively and therefore effectively to chemotherapy. This has the task of acting as a cytotoxin on the division of the cancer cells and destroying them. In most cases, polychemotherapy is administered with several different individual substances in various combinations.

Patients can be given chemotherapy in the form of capsules, tablets, injections or infusions. Treatment is carried out in several chemotherapy cycles (4-6 cycles) according to a fixed schedule. Between the individual therapy cycles there are therapy-free intervals in which the patient can recover.

Unfortunately, chemotherapy not only affects tumour cells, but also healthy cells in the body, which divide rapidly. As a result, side effects such as hair loss, damage to the intestinal mucosa or blood count changes occur, usually temporarily, but in rare cases also persistently. Regular blood count checks are necessary in order to recognise a deterioration in the blood count in good time and, for example, to initiate preventive measures to prevent infections. They can also help to customise the intensity of chemotherapy.

In many patients, partial or even complete remission (regression/disappearance of the tumour mass) could be achieved through polychemotherapy. The average survival time could thus be significantly extended. Patients with a 'limited disease' tumour have the best chances of recovery.

In the case of advanced lung cancer, palliative chemotherapy can alleviate symptoms and prolong life. The choice of cytostatic drugs depends largely on the patient's general condition.

It has recently been shown that the addition of checkpoint inhibitors ("immunotherapy") to chemotherapy can slightly improve survival in patients with extensive disease.

For each tumour patient, the attending physician will draw up an individual treatment plan that is not only geared to the characteristics of the tumour, but also to the patient's physical and psychological resilience and can be adapted accordingly.

Studies: Numerous new drugs and innovative treatment methods are constantly being developed. New drugs are also available at Ulm University Hospital as part of clinical trials for the treatment of lung cancer

Radiotherapy (radiotherapy)

Radiotherapy, like chemotherapy, aims to destroy the cancer cells. A high but targeted concentration of radiation is used to damage the cancer cells while sparing the healthy tissue.

If patients with a localised tumour are in partial or even complete remission (disappearance of the tumour) after successful chemotherapy, radiotherapy can help to stabilise the disease status.

The combination of chemo-immunotherapy and radiotherapy has led to an increase in survival time, a higher cure rate and longer relapse-free periods.

Radiotherapy is usually carried out on an outpatient basis over several weeks in small individual doses. This ensures gentle treatment of healthy tissue. After radiotherapy, side effects such as reddening of the skin, discolouration of the skin, hardening of the subcutaneous tissue, difficulty swallowing (oesophagus radiation field), inflammation of lung tissue, scarring of lung tissue (pulmonary fibrosis) with coughing and a reduction in breathing capacity and, in very rare cases, a reduction in cardiac output if the heart was also in the radiation field can occasionally occur.

Surgery

Surgical therapy plays only a minor role in small cell lung carcinoma. Only in stage I is primary surgery followed by systemic therapy indicated for peripheral tumours.

Surgery alone is always an inadequate therapeutic measure for small cell lung carcinoma.

In rare cases, the spread of the tumour can lead to bleeding or persistent infections of the lung tissue. If the patient is in good general health and non-invasive therapy fails, palliative surgery can provide relief.

Treatment of non-small cell lung carcinoma
(approx. 75-80% of lung carcinomas)

The treatment of non-small cell lung carcinoma depends on the stage of the tumour. In stages I and II, surgical removal of the tumour is the standard treatment. Depending on the tumour stage, postoperative chemotherapy or, in certain cases, targeted therapy (adjuvant therapy) can further improve the chances of cure and recurrence-free survival. In stages IIIA and IIIB, the lung carcinoma can also be surgically removed under favourable circumstances, but an extended treatment plan is often necessary, which includes chemotherapy, radiotherapy with subsequent immunotherapy and/or surgery as treatment options. In the most advanced stage IV with distant metastases, chemo-immunotherapy is usually given, possibly supplemented by radiotherapy.

For some subtypes of non-small cell lung cancer with certain genetic changes, drugs have been developed that enable targeted therapy against an existing genetic change in the tumour.

The following genetic alterations in lung cancer can currently be treated with targeted therapy: ALK translocations, BRAF-V600E mutation, EGFR exon 18-21 mutations, NTRK fusions, RET translocations, ROS1 translocations. C-Met exon 14 skipping mutation.
Further targeted approaches are in development and some are already close to authorisation.

For tumours without genetic changes, chemo-immunotherapy is currently considered the standard of care in most cases.

Surgery

Surgery can be considered as a curative (healing) operation, especially in the early stages, if the tumour is still localised. In some cases, pre-treatment with chemotherapy or radiotherapy can also help to shrink the tumour and then perform curative surgery. These decisions are always discussed on an interdisciplinary basis in our tumour board.

The extent of the operation always depends on various factors. The location of the tumour, your general condition and the functionality of the remaining lung.

• Curative surgery:
  Complete removal of the lung carcinoma offers the best chance of a cure. Up to tumour stage IIB, it is usually possible for the surgeon to completely remove the tumour with a sufficient safety margin without disproportionately impairing the function of the lung. However, the actual extent of the tumour can only be determined with certainty during the operation and the further procedure can sometimes only be decided at this point at short notice. In some cases, surgery can also be performed at a more advanced stage of the tumour. Depending on the spread of the disease, the operation can be more or less extensive. Sometimes individual lobes of the lung have to be removed, in less favourable cases an entire lung.
• Palliative surgery:
  In rare cases, the spread of the tumour can lead to bleeding or persistent infection of the lung tissue. If the patient is in a good general condition and alternative therapies have failed, surgery can also help here. The aim of this palliative operation is to alleviate symptoms.

Radiotherapy (radiotherapy)

Primary radiotherapy (radiotherapy as the first therapy) is carried out if the lung tumour cannot be surgically removed.

Secondary radiotherapy (radiotherapy as a second therapy) is used if the tumour could not be completely removed surgically and the remaining tumour cells in the body need to be destroyed.

Adjuvant radi otherapy (radiotherapy after an operation) is carried out if the primary operation has revealed a larger lymph node involvement (N2). As a rule, adjuvant radiotherapy is carried out after adjuvant chemotherapy in these patients with the aim of improving tumour-free survival.

Palliative radiotherapy: In the case of painful metastases or bone metastases that pose a threat to the stability of the bone, radiotherapy can often bring about a rapid improvement in symptoms.

Combined radiochemotherapy

The combination of radiotherapy with drug tumour therapy is more effective than radiotherapy alone. The choice of medication depends on the patient's co-morbidity.

Chemo-immunotherapy

Adjuvant chemotherapy (administered after surgery):
In patients with tumours in tumour stage II-III, chemotherapy is indicated after surgery to further improve the chance of recovery.

Adjuvant immunotherapy:
Immunotherapy should be administered to patients after radiochemotherapy for a further year.

Neoadjuvant chemotherapy (administered before surgery):
Studies have shown that in the case of advanced non-small cell lung cancer, neoadjuvant chemotherapy (administered before surgery) can sometimes create better conditions for surgery. In the best case scenario, the tumour is reduced in size by the chemotherapy and can therefore be removed more safely by surgery.

Palliative chemo-immunotherapy:
Palliative chemotherapy for patients with metastasised non-small cell lung carcinoma is gaining in importance thanks to new drugs. Modern chemotherapeutic agents are well tolerated and can prolong life and improve or delay the onset of tumour-related symptoms. Immunotherapy (checkpoint inhibitors) activates the body's own immune cells to fight tumours.

Studies: Numerous new drugs and innovative therapy methods are currently being developed. New drugs are also available at Ulm University Hospital as part of clinical trials for the treatment of lung cancer. (Study centre)

If the disease progresses during the first course of chemotherapy, it may make sense to switch to other drugs. A combination of chemotherapy with the substances nintedanib or ramucirumab may be possible as a targeted therapy in the second line of therapy.

Palliative bronchoscopic therapy for lung cancer

Bronchoscopy is increasingly being used not only for diagnosis, but also as a palliative therapy to provide patients with relief. If the airways are blocked by secretions, tissue or blood, various methods such as aspiration of secretions, compression of bleeding sources, laser removal of tumour tissue, insertion of tubes (stents) to keep constricted areas open can make breathing much easier for the patient.

The treatment of cancer (surgery, radiotherapy and drug-based tumour therapy) as well as existing concomitant diseases can lead to treatment-related disorders of varying degrees of severity in patients. They can be alleviated by targeted rehabilitative measures in the somatic and psychosocial areas.

You will be informed about the possibilities of outpatient and inpatient rehabilitation options by your attending physician or the social services at the hospital.

The aim of aftercare is the early diagnosis of a recurrence (recurrence of the tumour) and the detection of side effects of the therapy. After curative therapy, the aim of follow-up care is also the early diagnosis of a second tumour.

Follow-up care is carried out at 3-monthly intervals in the first year after treatment. From the 2nd year onwards, follow-up care is then carried out at six-monthly intervals.

The follow-up examination includes an interview, physical examination, basic laboratory tests and an imaging examination of the lungs. Further examinations can be added by the treating doctor depending on the assessment of the risk of relapse and symptoms.

If a tumour recurs after successful treatment of lung cancer, the course of treatment is similar to that when the disease is first diagnosed.
Examinations are carried out to determine the spread of the tumour in the body. Depending on the treatment already carried out at the time of initial diagnosis, the attending physician will then draw up an individualised treatment plan, which will include one or more of the options described in the "Therapy" section.