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The histological subtype of the tumour can influence the type of treatment you will receive. For example, non-squamous cancers may benefit from certain anticancer therapies that have been shown to be effective only in patients with this histological subtype. Grade Grade is based on how different tumour cells look from normal lung cells, and on how quickly they grow. The grade will be a value between one and three and reflects the aggressiveness of the tumour cells; the higher the grade, the more aggressive the tumour. Biological testing of the tumour Tissue specimens from metastatic NSCLC belonging to the non-squamous subtype should be tested for the presence of specific mutations in the EGFR gene. Even though such mutations are rare (approximately 10–20% in Caucasians with adenocarcinoma), the detection of an EGFR gene mutation has important prognostic and therapeutic implications in patients with metastatic NSCLC. EGFR testing is not recommended in patients with a diagnosis of SCC, except in never-, long-time ex- or light smokers (<15 pack years). Tissue should also be tested for the presence of a specific mutation (known as V600E) in the BRAF gene, as therapies are available to treat tumours with this mutation (Planchard et al., 2018). Routine testing for rearrangement in the ALK and ROS1 genes is now standard of care and should be carried out, if possible, in parallel with EGFR mutation analysis. ALK rearrangement is more frequent in people who have never smoked, those with the adenocarcinoma subtype (5%) and in younger patients (aged ><50 years old). Detecting ALK rearrangements has important therapeutic implications for patients with metastatic NSCLC due to the existence of drugs targeting ALK (e.g. crizotinib, ceritinib and alectinib) (Planchard et al., 2018; Novello et al., 2016). Some ALK inhibitors, including crizotinib, also inhibit ROS1, therefore the presence of ROS1 rearrangements also guides treatment decisions in metastatic NSCLC (Planchard et al., 2018). Programmed death-ligand 1 (PD-L1): This is a cellular protein thought to be involved in helping the tumour to evade detection by the body’s immune system. The amount of PD-L1 present in a tumour may influence the decision to treat the cancer with anti-PD-L1 immunotherapy. 20 Non-small-cell lung cancer Who is involved in planning my treatment? In most hospitals, a team of specialists will plan the treatment they feel is best for your individual situation. This multidisciplinary team of medical professionals may include: • A surgeon. • A medical oncologist (a doctor who specialises in the medical management of cancer). • A radiation oncologist. • A chest physician. • A nurse specialist. • A radiologist (or radiographer) who has been involved in the assessment of any x-rays and scans. • A pathologist who has been involved in the analysis of your tumour biopsy. • A molecular biologist who has been involved in the genetic analysis of your tumour biopsy. • A psycho-oncologist to provide psychiatric assessment and counselling. Other services that may be offered include: a dietician, a social worker, a community care nurse, a physiotherapist, a clinical psychologist and a palliative care service (who can assist with pain management). After consultation with the multidisciplinary team, your doctor, possibly with other members of the care team, will talk to you about the best treatment plan for your situation (Planchard et al., 2018). They will explain the benefits and potential drawbacks of different treatments. It is important that patients are fully involved in the treatment decision-making – when there are several treatments available, doctors should involve patients in making decisions about their care so that the patients can choose the care that meets their needs and reflects what is important to them. This is called ‘shared decision-making’. It is important that patients are fully involved in discussions and decisions about their treatment Your doctor will be happy to answer any questions you have about your treatment. Three simple questions that may be helpful when talking with your doctor or any healthcare professional involved in your care are: • What treatment options do I have? • What are the possible benefits and side effects of these options? • How likely am I to experience these benefits and side effects? 21 ESMO Patients Guide What are the treatment options for NSCLC? Aims of treatment In early-stage NSCLC, when the cancer is confined to the lung and therefore considered to be curable, the main treatment is surgical resection (Postmus et al., 2017). For locally advanced NSCLC, multimodal therapy is usually adopted to help shrink or in some cases completely remove the cancer (Eberhardt et al., 2015). For metastatic NSCLC, when the cancer has spread to other parts of the body, and cure is not an option, various systemic anti-cancer treatments may be used in an attempt to slow down tumour growth and improve symptoms and quality of life – this is called supportive or palliative care (Planchard et al., 2018). Overview of treatment types Treatments for NSCLC include surgery, radiotherapy, chemotherapy and targeted therapies The treatment you receive will depend on the stage and type of cancer, as well as your general health and treatment preferences, which will be discussed together with your doctor. You may have a combination of treatments. The main types of treatment are listed below: • Surgery may be possible to remove NSCLC if it is diagnosed at an early stage. The type of operation that is offered will depend on the size and location of the cancer (Postmus et al., 2017): - A wedge or segment resection is the removal of a very small amount of the lung; this is sometimes offered if the cancer is at a very early stage - A lobectomy is the removal of one of the lobes of the lung; it is the standard surgical treatment for NSCLC - A pneumonectomy is the total removal of one of the lungs; it is a more complex surgical resection than lobectomy or wedge (segment) resection. • Chemotherapy works by disrupting the way that cancer cells grow and divide. However, these drugs can also affect normal cells. Chemotherapy can be given before or after surgery for NSCLC. Some people have chemotherapy at the same time as radiotherapy – this is called chemoradiotherapy. Chemotherapy may be given to try to cure the cancer or to prolong life and control symptoms (palliative care) (Postmus et al., 2017; Planchard et al., 2018). • Targeted therapies and antiangiogenic therapies are drugs that block specific signalling pathways in cancer cells that encourage them to grow (Novello et al., 2016). 22 Non-small-cell lung cancer • Immunotherapies are treatments that block inhibitory pathways which restrict the body’s immune response to cancer, thereby helping to reactivate the body’s immune system to detect and fight the cancer (Novello et al., 2016). • Radiotherapy is a type of treatment that uses ionising radiation, which damages the DNA of cancerous cells, causing the cells to die. It may be used instead of surgery to try to cure early-stage NSCLC. Radiotherapy can be given after chemotherapy or concurrently (chemoradiotherapy). Radiotherapy is also used to control symptoms when the cancer is more advanced or has spread to other parts of the body. There are various different techniques for delivering radiotherapy, including stereotactic ablative radiotherapy (SABR) (when available), a type of external beam radiation therapy that delivers a high dose of radiation specifically to the tumour (Postmus et al., 2017; Planchard et al., 2018). Your doctor and nurse specialist can discuss all of the possible treatment options available to you to help you to make an informed decision about the best way forward for you. The response to any treatment you receive will be assessed regularly to see how effective the treatment is and to check whether the benefits outweigh any side effects that you might experience. Evaluation of response is recommended after 6–12 weeks of systemic anti-cancer treatment for Stage IV NSCLC. This relies on repetition of the initial imaging tests that showed the cancer (Novello et al., 2016; Planchard et al., 2018). 23 ESMO Patients Guide Treatment options for early (Stage I–II) NSCLC Early-stage NSCLC that is confined to the lung may be curable with surgery Surgery is the main treatment approach for early-stage NSCLC (Postmus et al., 2017). This involves removing the cancer and some of the nearby lymph nodes in the chest. The number of lymph nodes removed is dependent on the type of surgery performed. Surgical resection of NSCLC is a major operation and you need to be in good general health to be able to cope with it. The type of operation will either be a lobectomy (preferred) or a wedge (segment) resection and may be carried out via open surgery or video-assisted thoracic surgery (VATS), depending on the preference of your surgeon. VATS is generally the preferred choice for Stage I tumours (Postmus et al., 2017). The lymph nodes removed during surgery will be examined under a microscope to check for cancer cells. Knowing if the cancer has spread to the lymph nodes also helps your doctors decide if you need further treatment with adjuvant chemotherapy or radiotherapy (Postmus et al., 2017). Adjuvant chemotherapy is typically given to patients with Stage II NSCLC and may be considered for some patients with Stage IB disease. Your general health and your postoperative recovery will be taken into account when deciding whether you should be offered adjuvant chemotherapy. A combination of two different drugs is preferred (one of them being cisplatin), and it is likely that you will be offered 3 or 4 cycles of treatment (Postmus et al., 2017). Adjuvant radiotherapy may be given after surgery in patients with Stage II NSCLC (Postmus et al., 2017). In patients with Stage I NSCLC who are unwilling or unable to undergo surgery, SABR may be offered. This treatment will be given to you as an outpatient over 3–8 visits. If your tumour is larger than 5 cm and/ or is located at the centre of the lung, radical radiotherapy using more conventional daily or accelerated schedules is preferred (Postmus et al., 2017). 24 Non-small-cell lung cancer Treatment of early (Stage I–II) NSCLC – summary (Postmus et al., 2017) TREATMENT TYPE PATIENTS TREATMENT DETAILS CONSIDERATIONS Surgery Stage I or II NSCLC • Operation is either: - Lobectomy: The removal of one of the lobes of the lung (preferred option), or - Wedge or segment resection: Only a small amount of the lung is removed (sometimes used for very early NSCLC) • Carried out either by open surgery or by VATS • Risks associated with major surgery • Recovery time (shorter with VATS) • Usually able to go home 3–7 days after surgery • Requires post-operative pain control Adjuvant chemotherapy Stage II NSCLC, following surgery Stage IB NSCLC following surgery, if primary tumour is >4 cm in size (Not recommended in Stage IA NSCLC) • A combination of two different drugs usually given intravenously (one of which is cisplatin) • Typically, 3–4 cycles of treatment • Need to recover from surgery before starting chemotherapy • Pre-existing medical conditions may affect whether you will be suitable for chemotherapy SABR Preferred for Stage I, if surgery not carried out • More precise than conventional radiotherapy; very small areas can be targeted with a high dose • Shorter treatment time vs conventional radiotherapy (2-week course) • SABR is associated with low toxicity in patients with COPD and in elderly patients • Surgery may be offered afterwards if SABR is not successful or if there are complications Radical radiotherapy Tumours >5 cm and/or centrally located Following incomplete surgery • Conventional (4–7-week course of treatment of short, daily sessions Monday to Friday) or accelerated schedule (an increased number of treatments delivered over a shorter timeframe) COPD, chronic obstructive pulmonary disease; NSCLC, non-small-cell lung cancer; SABR, stereotactic ablative radiotherapy; VATS, video-assisted thoracic surgery 25 ESMO Patients Guide Treatment options for locally advanced (Stage III) NSCLC Treatment for locally advanced disease is likely to involve different types of therapy Locally advanced NSCLC represents a very diverse disease (see Stages IIIA and IIIB in the AJCC/UICC staging system table) and so it is not possible to recommend a ‘one size fits all’ approach to treatment. Some patients with Stage III NSCLC have a tumour that is considered resectable, i.e. your doctor/surgeon thinks that it can be completely removed by surgery either straight away or after a course of chemotherapy (with or without radiotherapy). On the other hand, some patients with Stage III NSCLC have a tumour that is considered unresectable, i.e. surgery is not possible due to the size/location of the tumour and involvement of lymph nodes in the middle of the chest.