Understanding Metastatic Disease

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1 Supported by an unrestricted educational grant from Pfizer

2 Understanding Metastatic Disease Metastatic disease or metastases are phrases that mean the same as Secondary cancer. This means that the cancer has spread from the original Primary site to another part of the body. In this booklet we will look at how this happens, how it is measured, and what it means for the patient.

3 Cancer cells Tumours form when some cells in the body start to behave differently from normal cells. These cells divide and reproduce in an unusual way, and form a lump, known as a tumour. Tumours can be benign or malignant. If a tumour is benign, the cells will not spread to other parts of the body, and so are not cancerous. A benign tumour can still cause problems by growing and pressing on nearby organs. A malignant tumour is made of cells that have the ability to spread to other parts of the body. If it is left untreated, it may spread to surrounding tissue, or some of the cells may break away and start reproducing somewhere else. Metastatic comes from the Greek words Meta meaning change and Stasis meaning place. Staging and Grading of cancers When a person is diagnosed with cancer, the doctor will identify the primary site of cancer. As this tumour grows, it is possible that some cells will break away and form metastases. Almost half of all cancers metastasise or spread to other parts of the body. Cancerous cells can metastasise anywhere in the body but some organs are more commonly affected by metastases. What is a Primary Cancer? Cancers are named and treated according to the type of cell in which they start. This is called the Primary Cancer. For example, if someone has a cancer that starts in the lung, then this is their Primary Cancer. What is Metastatic Cancer? If the primary cancer spreads from its original site to another part of the body, such as the liver, this secondary cancer is known as Metastatic cancer or disease, or metastases. The term comes from the Greek words Meta meaning change and statis meaning place. How does cancer spread? There are three ways in which cancers can spread. Firstly they can simply grow and invade into adjacent tissue. Secondly tumour cells can break away and spread through the lymphatic vessels and become trapped and grow in lymph glands near the primary tumour. The lymphatic system is part of the immune system. It is made up of organs, such as bone marrow, the thymus, the spleen, and lymph nodes. The lymph nodes (or glands) are connected by a network of tiny lymphatic ducts. It is through these ducts that the cancer cells can move. Finally tumour cells can travel through the blood stream to distant sites such as the liver or the lung and become trapped and grow to form metastasis. Staging is a way of describing how big the tumour is and whether it has spread. Staging can be performed by special scans or by examining the tumour removed at surgery. A biopsy can only give information on the grade but not the stage of the tumour. Tumour grading is a system used to classify cancer cells in terms of how abnormal they look under a microscope. Grade can indicate how quickly the tumour is likely to grow and spread. Both stage and grade are important in defining prognosis and treatment. 2 3

4 TNM Staging System Staging is tumour-specific, although the nomenclature is common. TNM is the usual means of defining stage. In the TNM staging system, each type of cancer is assigned a T category, an N category and an M category. The letters in TNM staging represent the following: T stands for Tumour. T staging gives details about the original tumour (the first tumour found, before spreading may have occurred). TX means the tumour cannot be evaluated. T0 means there is no evidence of an original tumour. TIS means the cancer is in situ, or, has not spread. T1 to T4 describe the tumour size. The bigger the number, the larger the tumour is. N stands for Nodes. N staging determines whether or not the cancer has spread into nearby lymph nodes. NX means the nearby lymph nodes cannot be evaluated. N0 means there is no evidence of cancer in the nearby lymph nodes. N1 to N3 describes the extent of spread into the lymph nodes (for instance, the location, size and number of lymph nodes affected). The higher the number, the more lymph nodes are affected. M stands for Metastasis. M staging determines if the cancer has metastasised, or spread, beyond the lymph nodes into other parts of the body (also known as distant metastasis, or distant spreading). MX means distant spread cannot be evaluated. M0 means there is no evidence of distant spreading. M1 means distant spread has been found. Overall Cancer Stage After the doctor determines the TNM staging of the cancer, he or she assigns an overall cancer stage of I, II, III or IV. For instance, breast cancer that is less than 2 cm in size and has not spread to the lymph nodes or other parts of the body would be categorized as T1, N0, M0 and considered stage 1 breast cancer. The higher the overall cancer stage, the more advanced the cancer is. The TNM staging classification system works differently in certain types of cancer, so talk to your doctor if you would like to learn more about cancer staging in your specific type of cancer. Difficulties in Rare Cancers with TNM Because a number of rarer cancers do not have definitive classifications at present (e.g. neuroendocrine cancers and tumours arising in the head and neck region), and because these tumours can have diverse clinical behaviours and outcomes, it can be difficult to implement a uniform staging system for these cancers. Relatively low patient numbers can mean that the data is not available to analyse or back up important clinical questions. This means that changes in the TNM staging system have to be developed based on expert opinions and published reports in the literature while taking advantage of advances in technology for improved assessment of tumour extent and improvements in treatment. Some cancers, such as leukaemia, do not form solid tumours, so the TNM staging system is not useful. A significant number of tumours are classed as Cancers of Unknown Primary (CUP). This means that a patient is diagnosed with metastatic cancer, but the primary site is unknown. Sometimes it is possible to identify the original cancer, by looking at the cells under a microscope, or by looking for tumour markers (blood tests). In some cases the cells may be so abnormal or poorly differentiated that it may be impossible to find out where in the body the cancer first grew. In these instances, the TNM system cannot be used. Examples of cancer in which the primary can be hard to detect are melanoma and lymphoma. 4 5

5 Examples of Staging System in Rare Cancers For some rarer cancers, the staging system is well defined. These include pancreatic, testicular and kidney cancer. Here is an example: The T stages of kidney cancer The T stages are T0 - there is no evidence of a primary tumour in the kidney T1 - the tumour is no more than 7cm across and is completely inside the kidney T2 - the tumour is more than 7cm across, but is still completely inside the kidney T3 - the cancer has spread through the kidney capsule, to a major vein, the adrenal gland or other tissues immediately surrounding the kidney T4 - the cancer has spread further than the tissues immediately surrounding the kidney You may hear your doctor talk about T1a or T1b. T1a means you have a tumour that is less than 4cm across. T1b means the kidney tumour is between 4 and 7cm across. This is being introduced because it is important for surgeons. If you have a smaller tumour, it may be possible to remove just the cancer and leave the rest of the kidney behind (nephron sparing surgery). The N stages of kidney cancer These tell the doctor if the cancer has spread to your lymph nodes. There are four lymph node stages in kidney cancer. These are N0 - No cancer in any lymph nodes N1 - Cancer spread to one nearby lymph node only N2 - Cancer spread to more than one nearby lymph node Doctors often call lymph nodes that contain cancer positive lymph nodes. If you have cancer in your lymph nodes, then your kidney cancer has begun to spread. Your doctor may want you to have further treatment after your surgery. The M stages of kidney cancer As with most cancers, there are two stages for metastases (or cancer spread). Either the cancer has spread (M1) or it hasn t (M0). If your cancer has spread, then you have advanced kidney cancer. The number stages - stage 1 to stage 4 By combining the T, N & M staging of your tumour, your doctor will give it an overall stage. This is important for deciding which treatment is best for you. There are 4 stages for kidney cancer. They are Stage 1 - The cancer is less than 7cm across and is completely inside the kidney Stage 2 - The cancer is more than 7cm across but is still completely inside the kidney Stage 3 - The cancer has grown into the adrenal gland, or one of the major veins nearby. There is no more than one nearby lymph node containing cancer cells Stage 4 - The cancer has grown into the surrounding tissues and there is more than one lymph node containing cancer cells OR the cancer has spread to another part of the body Doctors tend to use Roman numerals for writing down cancer stage. So you may see stage written as I, II, III, or IV. 6 7

6 Tumour grading The grade of your cancer is decided by the appearance of the cancer cells under the microscope. The more they look like normal cells, the lower the grade of your cancer. The more abnormal (and so less like normal cells) the cancer cells look, the higher the grade of your cancer. Generally speaking, low grade cancers tend to grow more slowly and are less likely to spread than high grade cancers. Histological grade, also called differentiation, refers to how much the tumour cells resemble normal cells of the same tissue type. Nuclear grade refers to the size and shape of the nucleus in tumour cells and the percentage of tumour cells that are dividing. NorMaL cells cancer cells Low grade means the cancer cells tend to be slow growing, look quite similar to normal cells (are well differentiated), tend to be less aggressive, and are less likely to spread quickly. Intermediate grade is a middle grade. High grade means the cancer cells tend to be fast growing, look very abnormal (are poorly differentiated), tend to be more aggressive and are more likely to spread quickly. Large cytoplasm Single nucleus Single nucleolus Fine chromatin Small cytoplasm Multiple nuclei Multiple and large nuclei Course chromatin The grade is more important for some kinds of cancers than for others, for example, knowing more about the grade of certain brain tumours, prostate cancer and lymphomas will help the doctor choose the best treatment options and arrive at a more accurate prognosis. The grade of your cancer is decided by the appearance of the cancer cells under the microscope. 8 9

7 The role of treatment in metastatic disease? There are numerous treatment options available for people with cancer that has metastasised. Working with your team, an appropriate treatment plan can be chosen. The best option will depend on where the cancer has spread to, the extent of cancerous cell growth, and the level of damage to the body. It will also depend on other features of the cancer, such as its drug receptor status and its aggressiveness. The initial goal maybe to stabilise the disease. To accomplish the treatment goal, it is important for the doctor to consider each individual s health and treatment history. There are alternative treatment categories. There are numerous treatment options available for people with cancer that has metastasised. Systemic therapies affect the entire body instead of just focusing on the location of the metastases. These therapies are intended to kill all cancerous cells, including microscopic cancerous cells circulating in the blood system that can travel to, and grow in, distant parts of the body. Examples of these therapies are chemotherapy, radionuclide therapy and immunotherapy. Local therapies including radiation and surgery, can be used to target cancerous cells in very specific areas of the body. Surgery is generally performed to remove a cancerous growth; however, surgery can also be performed to relieve symptoms. The type of surgery chosen will depend on the size of a tumour and its location. A tumour may be operated on to relieve some of the pressure caused by either a painfully pressed nerve, such as one pressing on the spinal cord, or by the expansion of an organ, such as the liver. Doctors may also need to remove a part of the affected organ. Some tumours cannot be operated on due to size, formation or location as they may be attached to a vital part of the body, such as a main artery that does not allow for removal

8 The role of treatment in metastatic disease? cont. Does metastatic disease affect prognosis? Clinical Trials are a step-by-step process that involves collecting and examining information. Research into rarer cancers is vital to improve understanding of the specific disease and how it can be treated, and aims: To understand what causes the cancer To understand how the cancers form To formulate more effective diagnostic scans and tests To discover new treatment options, and to ensure that current treatments are being implemented to provide the best therapeutic benefit If a patient wants to take part in a clinical trial, they should discuss this with their specialist, who will know whether they are eligible. All studies are run on strict inclusion and exclusion criteria for the safety of the patients. It can be frustrating for a patient to discover that they are ineligible, but no medical professional is able to influence any decisions based on these criteria. No one should ever include a patient in a clinical trial without their knowledge. A doctor, nurse or other researcher will ask for permission, and they can t enter a patient into the trial unless they have given their consent. To help a patient decide whether they want to take part, the researchers should tell them all about the study: what it is trying to find out how they will be treated what they will have to do. Being part of a clinical trial means that you are part of a treatment programme that is not usually being used. It may be a new treatment, or a new way of giving the treatment, or a new way of combining existing treatments with the trial drug. Alternative therapies also referred to as complementary and holistic therapies look at the healing of an individual s body, as well as the mind and spirit. None of these alternative therapies offer a cure, but practices such as yoga, acupuncture and homeopathy may help to improve your sense of well-being. The British Complementary Medicine Association (BCMA) has a searchable database of therapists, and is a good place to start. P.O. Box 5122, Bournemouth BH8 0WG Phone: Website: If there is no sign that the cancer has spread beyond the primary site then it may be possible to cure the patient by surgical removal of the tumour. In some cases cancer cells have already spread but cannot be detected on a scan because the cells are too small. However these cells may grow years after the primary is removed and form metastasis (secondary cancers). For most cancers it is difficult to cure patients who have metastasis although drug treatment may control the cancer growth. For this reason the prognosis is worse if metastases are present

9 Coping with the Emotional Challenges of Metastatic Disease Metastatic disease can be diagnosed at the same time as primary cancer or any time after the primary cancer diagnosis. If your cancer has come back, you may feel a multitude of emotions. Expressing any feelings you may have is both normal and understandable, and sharing them with friends and family may help. If negative feelings become overwhelming, it may be a good idea to talk to your GP, or a qualified counsellor. Speaking with others who are going through a similar experience can really help, so it may be worthwhile asking your doctor about local support groups, or looking on the internet for online organisations for people with your type of cancer. Supporting The Rarer Cancers Foundation PLease support our Work By sending a donation To The charity I am enclosing a cheque for Other Made payable to The Rarer Cancers Foundation gift aid declaration Please complete details and sign below if relevant I want The Rarer Cancers Foundation (Registered Charity Number ) to treat this donation, and all other donations I make from the date of this declaration until I notify you otherwise, as Gift Aid donations. Note: You must pay an amount of income tax and/or capital gains tax at least equal to the tax that the charity reclaims on your donations. PLease Use BLock capitals Name Address Postcode Speaking with others who are going through a similar experience can really help. Signed Date Please post your signed cheque and completed form to: The Rarer Cancers Foundation, The Great Barn, Godmersham Park, Canterbury, Kent CT4 7DT 14

10 Further information Acknowledgments PLease Tick BeLoW if you WoULd Like Us To send you further information The rarer cancers foundation is grateful To The following for Their helpful comments on The draft BookLeT: Other Rarer Cancers Foundation publications and resources Giving regular donations to The Rarer Cancers Foundation Remember The Rarer Cancers Foundation in your Will Ideas for local fundraising and sponsorship events Joining The Rarer Cancers Foundation Joining The Rarer Cancers Foundation Patients Army. This is a group of volunteers we can contact to help us in our work. We will contact volunteers individually to discuss the particular ways in which they might be able to help us. Dr Tim Meyer, Senior Lecturer in Medical Oncology UCL Cancer Institute, University College, London; Gwen Harlow, Chair of Trustees and Patient Advisor, The Rarer Cancers Foundation; The booklet was written by Catherine Bouvier RGN, Specialist Nurse Consultant, The Rarer Cancers Foundation. The Rarer Cancers Foundation 2010 PLease Use BLock capitals Name Address Postcode Telephone Cancer type or reason for interest in The Rarer Cancers Foundation: Please post your completed form to: The Rarer Cancers Foundation, The Great Barn, Godmersham Park, Canterbury, Kent CT4 7DT

11 The Rarer Cancers Foundation offers advice and information to individuals with rare and less common cancers or to their families and friends. The charity facilitates supportive networking, raises awareness of rarer and less common cancers and works to ensure that people with rarer cancers have access to the best possible services. Registered charity No The Rarer Cancers Foundation 2010 incorporating Rarer Cancers Forum

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