How is cancer diagnosed?

The great majority of cancers are discovered because of the symptoms that they cause, or because the person concerned (or their doctor) notices a lump or other abnormal appearance. A small but growing proportion of cancers are discovered as a result of doing tests on apparently healthy people who have noticed nothing abnormal. This is called ‘screening’.

SYMPTOMS

Most of the symptoms that can be caused by cancer are far more commonly the result of relatively minor illnesses that have nothing to do with cancer. Sometimes this means that the individual concerned does not take them seriously to start with, and so delays seeking medical advice.
Even when he or she does go, the general practitioner may not always feel that it is appropriate to consider cancer very seriously as a possible diagnosis at this stage.
There is really no way around this. Very thorough and immediate investigation of any symptom that might possibly be caused by a cancer would rapidly cause the health service to grind to a halt, not to mention causing a lot of unneces­sary anxiety.
Your doctor is more likely to suspect the possibility of a potentially serious cause for a symptom if it persists, or if you have certain other symptoms as well. Some symptoms are sufficiently likely to have a serious explanation that they require further investigation as a routine matter.
Symptoms that could indicate the presence of a cancer include the following.

Persistent and unexplained:
• Cough
• Breathlessness
• Hoarse voice

 

• Difficulty with swallowing
• Pain
• Indigestion
• Weight loss
• Altered bowel habit
• Discharge from any orifice (for example, nipple or vagina)
• Fever

Any abnormal bleeding:
• Coughing up blood
• Rectal bleeding
• Vaginal bleeding between periods
• Vaginal bleeding with intercourse
• Postmenopausal vaginal bleeding
• Blood in the urine
• Bleeding from a mole.

Anyone who has any of the above symptoms should seek medical advice promptly. The majority of people with most of these symptoms will not have cancer, but if a cancer is present it is important to diagnose it as early as possible.

LUMPS AND BUMPS

The majority of cancers are fairly deep-seated within the body and only a minority can be felt on examination by a doctor, let alone by the patient. However, cancers that are nearer to the surface, such as those involving the breast or lymph glands in the neck or armpits, are often discovered by the person becoming aware of a lump. Most skin cancers are also noticed first by the person concerned rather than by his or her doctor.
In fact, few lumps or persistent skin changes turn out to be cancerous. However, if you do notice a lump in the breast, testis or elsewhere, or if you have a persistent or worsening unexplained ulcer or ‘spot’, particularly any change in appearance of a mole, you should seek medical advice promptly.

SCREENING FOR CANCER

Screening to discover cancers at an early and more curable stage can help to reduce the number of deaths from a few important types of cancer. However, screening has its problems. If your test result shows up an abnormality that eventually turns out not to be cancer, as often happens, you will have had to go through further investigations and you may have experienced a lot of unnecessary worry.

Screening can sometimes reveal the presence of a very slow-growing cancer or a pre-cancerous growth that would not in fact have caused any problems had it not been discovered. As a result some people may receive treatment that is not really necessary. Screening is expensive: usually a very large number of people have to be screened to discover one cancer for which earlier diagnosis makes the difference between the success and failure of treatment.

Breast cancer screening

Women over the age of 50 are offered mammography (see page 26) every three years up to the age of 65, and beyond on demand. The majority of abnormalities seen on the X-ray pictures are not cancerous, but further investigation of some of them is recommended, sometimes leading to removal of a small piece of tissue (a ‘biopsy’) for microscopic analysis. A few of these abnormalities are then discovered to be cancerous or pre-cancerous. The breast cancers discovered in this way are usually small and screening has been shown to improve significantly the chance of cure.

Cervical cancer screening

Sexually active women should have a cervical smear test every three to five years up to the age of 60 to 65. (Women who have never had sexual intercourse very rarely get this type of cancer.) When you have a smear test an instrument called a speculum is inserted into the vagina to enable the cervix (neck of the womb) to be seen. The cervix is then scraped gently with a wooden spatula to collect a reasonable number of cells. These are smeared on to a piece of glass and exam­ined under the microscope. The procedure may be a little un­comfortable, but is not normally painful. The test can discover pre­cancerous abnormalities which can easily be dealt with. It can also discover cancers at a very early stage, when the cure rate is high.
Most of the abnormalities discovered in this way are only minor changes, which may require no further investigation, or merely a repeat smear or more frequent smears for a while. However, some abnormalities require further investigation in a procedure called ‘colposcopy’, which involves examining the illuminated cervix with a type of magnifying glass. Tiny samples or ‘punch biopsies’ can be removed from any abnormal areas. This is briefly uncomfortable but it should not be painful and only lasts about 10 minutes.

If potentially pre-cancerous areas are discovered, further treatment to destroy the cells is recommended. This may involve ‘laser evaporation’ (a concentrated beam of light vaporises the abnormal cells), ‘cryotherapy’ (the abnormal cells are destroyed with a freezing probe) under local anaesthetic, or ‘diathermy’ (the abnormal cells are burnt by an electrical probe) under general anaesthetic.
In a small percentage of women the colposcopy may suggest that the abnormality is more serious and a ‘cone biopsy’ (removal of the central lining of the cervical canal) under a general anaesthetic may be necessary. This may well remove all the affected tissue but, occasionally, a more deeply infiltrating growth is discovered which requires more extensive treatment.
Very few women die from cancer of the cervix and, of those who do, almost 90 per cent have never had a routine smear.

Screening for other cancers

Recent research has shown that screening that detects bowel tumours at an early stage can cut the number of deaths from bowel cancer. This involves testing stool specimens for small amounts of blood which are not normally visible to the naked eye. Although the cause of such bleeding is usually something other than cancer, sometimes further investigation by colonoscopy or barium enema (see pages 23, 24, 26) will reveal the presence of a cancer before it has grown sufficiently to cause symptoms. It seems likely that such ‘faecal occult blood’ testing will become more widely available.
Screening for prostate cancer can be done by testing the blood for a chemical often produced by these cancers (‘prostate-specific antigen’ or ‘PSA’), and by a physical examination and ultrasound scanning. Screening can detect some prostate cancers at an early stage, but it can also result in unnecessary treatment. The prostates of most old men dying from other conditions can be found to contain small cancers. Most cancers occurring in elderly people are slow growing and are unlikely to cause problems during the remainder of an individual’s life if left untreated. However, recent evidence suggests that screening can reduce deaths from prostate cancer.
Screening for lung cancer by routine chest X-rays and microscopic examination of sputum for cancer cells has been proven not to be worthwhile. The majority of lung cancers appear to carry an unfavourable prognosis from an early stage and at present the best hope of significantly reducing deaths from this disease is through a reduction in smoking.

CANCER IN FAMILIES

In theory, it makes sense to screen people who are known (or who are likely) to have inherited a genetic predisposition to cancer. However, fewer than ten per cent of cancers have an inherited cause. Cancer is a common disease and, when it affects two or more members of the same family, the strong probability is that this is pure chance. Occasionally it may be the result of a shared environmental factor such as smoking.
Hereditary cancer may be suspected when two or more close relatives – parents, brothers or sisters – have either the same cancer or different ones that can sometimes be genetically related, such as those of the breast and ovary. Other hallmarks are the development of the cancer at a young age and a tendency to have bilateral (for example, in both breasts) or multiple tumours.
Some of those with a strong family history may have inherited certain identifiable abnormal genes. If they have, it is, however, by no means certain that they will develop a cancer, although inheriting some genes can give an 80 to 90 per cent or even higher risk of developing cancer at some stage. The same type of cancer can sometimes occur in two or more members of a family without any particular genetic abnormality being identifiable. The risk for other members of the family may then be increased, but not usually to a high level.
A predisposition to a variety of rare cancers can be inherited, for example certain tumours of the thyroid and other hormone-producing glands. As far as the more common types of cancer are concerned, the main types that are occasionally inherited are those of the large bowel (colon and rectum), the breast and the ovary. Bowel cancer can occasionally run in families through inheritance of a mutated ‘adenomatosis polyposis coli’ (APC) gene or ‘hereditary non-polyposis colorectal cancer’ (HNPCC) gene. Affected individuals develop multiple benign bowel polyps at an early age and these subsequently become malignant in almost all cases.
Breast cancer is inherited in only five to ten per cent of cases. So far two important breast cancer genes have been discovered: ‘BRCA-1’ and ‘BRCA-2’. A woman who has inherited a mutated BRCA-1 or BRCA-2 gene has about an 85 per cent chance of developing breast cancer at some stage. The mutated BRCA-1 gene also confers an increased risk of ovarian cancer. However, most women with a family history of breast cancer do not have an inherited BRCA-1 or BRCA-2 mutation. They may be at an increased risk of breast cancer, but the level of risk is usually much lower, for example below 30 per cent for those with a mother or sister with the disease.

If you are worried that you may be at an increased risk of cancer because of your family history, you should discuss this with your own doctor. If appropriate you may be referred for a specialised opinion from a clinical geneticist who may well be able to reassure you that you are not at a significantly increased risk. Alternatively, it may be possible to arrive at an approximate assessment of the level of any increased risk.
Occasionally it is appropriate to test for the presence of an abnormal gene by very sophisticated analysis of a blood sample. However, this is performed only if the individual concerned still wants it done after very detailed discussion of all the implications, which can be profound. These include consider­ation of what will be done if a cancer-predisposing gene is discovered, feelings about living with the certain knowledge of high risk, what other family members will be told, the consequences for parenthood and how eligibility for life insurance may be affected.
Recommendations as to what should be done for those individuals identified as being at high risk vary enormously according to the cancer concerned, individual circumstances and preferences. Someone who is facing a high risk of developing hereditary bowel cancer may well be advised to have their colon and rectum removed surgically in their teens or twenties, before the disease has had a chance to develop. When this is done, the small bowel can be joined to the anus, avoiding the need for a ‘stoma’.
For women with a high risk of breast cancer, choosing the best form of preventive treatment is less straightforward. Some women will opt for prophylactic (that is, preventive) removal of both breasts (bilateral mastectomy), but, although this does reduce sign­ificantly the chance of getting breast cancer, it is no guarantee. A few women have developed cancer in the small amount of breast tissue that is left behind after mastectomy. Some women opt instead for a programme of close surveillance involving regular physical examination by a specialist and mammography.
Women at increased risk of ovarian cancer may opt to have both ovaries removed surgically as a preventive measure (bilateral ‘oophorectomy’) but, surprisingly, this again is not guaranteed to prevent the disease. Screening to detect ovarian cancer at an early stage using ultrasound scanning and blood testing for the CA-125 ‘tumour marker’ produced by ovarian cancer is an alternative strategy.

MEDICAL ASSESSMENT

If your symptoms suggest the possibility of cancer, or if your doctor finds something unusual during an examination or as the result of a screening test, you will probably need further assessment and tests, depending on the circumstances. Some further investigation may be arranged by your GP, but at some stage you are likely to be referred to a hospital consultant for an opinion on what should be done next. What is appropriate can vary greatly from one individual to another.
Waiting for appointments, further investigations and their results can inevitably be very worrying, but support is usually available from a variety of people and organisations (see ‘Further care’ and ‘Further help’).

CLINICAL ASSESSMENT

If you do need further assessment, the first step is likely to be a consultation with a specialist in an outpatient clinic where you will be asked more detailed questions about any symptoms, such as their severity and duration. You can also expect to be asked about your general health and other aspects that may be relevant, such as previous illnesses, any medication you may be taking, present or past occupations, and your home circumstances. This ‘history taking’ will then usually be followed by a physical examination which will tend to concentrate on the part of your body that is giving cause for concern, although you may also have a more generalised examination.
This assessment does not always help in making a diagnosis, but sometimes the doctor will strongly suspect a cancer because he or she finds, for example, a lump that has particular features suggest­ing malignancy. The physical examination may include taking a look inside some part of your body using instruments: for example, your voice box (‘laryngoscopy’), rectum (‘proctoscopy’) or cervix (by gently inserting a speculum into the vagina).

FURTHER INVESTIGATIONS

Biopsy

Although a lump may feel or appear cancerous a definite diagnosis of cancer can usually be made only by a pathologist, a doctor who specialises in assessing cells and tissues by studying them through a microscope. He or she will recognise the characteristic changes in appearance that confirm that cancer is present.
The removal of a piece of tissue for diagnostic purposes is known as a ‘biopsy’. Part of a lump or, if feasible, a whole lump (excision biopsy) may be removed during an operation performed under local or general anaesthetic. Sometimes a thin core of tissue may be removed by a special type of needle device which avoids the need to cut into tissue with a scalpel.
Alternatively, cells from the abnormal tissue may be sucked (‘aspirated’) into a thin needle attached to a syringe. This is called a ‘fine needle aspiration biopsy’ and is usually only uncomfortable very briefly. The cells can then be smeared on to a glass slide. Cells for microscopic examination can also be obtained by scraping the tissue concerned, as in cervical smear testing, or from tissue fluids such as sputum, fluid surrounding the lung (‘pleural effusion’) or urine.
The microscopic examination of very thin processed slices taken from a lump of tissue is known as ‘histology’, whereas the exam­ination of a cellular smear is known as ‘cytology’. Histology can give rather more information because the pathologist is able to assess not only the appearance of individual cells (that is, the bricks) but also the way the tissue is constructed (the architecture).

Cytology is based on the appearance of individual cells. It is capable of establishing the presence of a cancerous process but gives less qualitative information than histology. It also suffers from the potential problem that the cells removed from abnormal tissue by fine needle aspiration may not be representative – the needle may not have sucked up any cancerous cells, even though some were actually present. This risk of a ‘false­negative’ result is not usually a problem with histology. However, a positive cytology result is usually sufficient to justify setting in train further treatment. For many cancers this will involve surgical removal, when tissue will become available for histological examination.

In addition to microscopic examination of tissue to establish the diagnosis, biopsies are also sometimes performed in an attempt to establish the extent of the disease. For example, someone who has a swollen neck gland diagnosed as lymphoma may undergo a bone marrow biopsy to see whether there are lymphoma cells in the marrow, because this could influence the choice of treatment.
Some women with breast cancer may undergo removal of a crucial lymph node from the armpit (‘sentinel node biopsy’), the node having been meticulously localised after injecting a dye and a radioactive substance into the primary tumour. If this sentinel node ‘draining’ the primary tumour is clear of cancer, it is highly likely that all the other nodes in the armpit will also be clear and the patient can then avoid further surgery.

 

Words ending in ‘-oscopy’

The term ‘-oscopy’ merely means ‘taking a look’ (skopein is Greek for ‘to see’). Most cancers arise from the inner lining of tubes or containers such as the voice box (larynx), air passages in the lungs (bronchi), swallowing tube or gullet (oesophagus), stomach (for which the medical adjective is ‘gastric’), large bowel (colon and rectum) and bladder (sometimes referred to as ‘cyst’). It is possible to inspect all these structures using a variety of instruments and to take biopsies from any suspicious areas. The names given to these inspections, together with the organs involved, are as follows:
• laryngoscopy: voice box
• bronchoscopy: lungs
• gastroscopy: stomach
• colonoscopy: colon
• sigmoidoscopy: the S-shaped lower end of the colon and rectum
• cystoscopy: bladder.

Other types of inspection include the following:
• nasendoscopy: the air passageway from the nostrils to the larynx
• mediastinoscopy: the tissues behind the breast bone or sternum to assess whether or not a lung cancer has spread to the lymph glands there
• colposcopy: the cervix or neck of the womb
• laparoscopy: the abdominal cavity.

Some of these can be performed in the outpatient clinic, some require sedation and some a general anaesthetic. Many now involve the use of fibreoptic technology, which enables the doctor to see down a flexible cable inserted gently into the relevant opening in the body, or through a small cut. Sometimes it is easier for your doctor to see, feel and assess the extent of the growth, and to take a biopsy while you are under a general anaesthetic. This is why examination under anaesthetic (EUA) is quite a common procedure.

Blood tests

These are unlikely to provide the doctor with much useful information to help make the diagnosis unless the malignancy is of the white blood cells themselves (leukaemia), or if the cancer is one of the few types that produce a characteristic chemical or ‘tumour marker’ which can be measured in the blood. These include some cancers of the prostate and testis, and myeloma.

Nevertheless, blood tests can be useful in providing some in­formation on your general state of health. Sometimes they can also suggest that a cancer may have spread to other organs such as the bones or liver. This is when the concentration of certain chemicals known as ‘enzymes’, normally released into the blood by these organs, is above the normal range as a result of damage caused by the cancer.
However, these tests are not foolproof – there are usually several possible causes of such abnorm­alities other than spread of the cancer.

X-rays and scans

Often the first clear indication of the presence of a cancer is an abnormal appearance on an X-ray, for example, an abnormal shadow on a chest X-ray caused by a lung cancer occupying a space that would normally be filled largely with air.

Tumours can also produce an abnormal breast X-ray (mammogram) and show up on a barium enema X-ray of the bowel.
A mammogram is an X-ray picture of the breast taken with the breast compressed between two flat plates. Breast cancers can produce recognisable signs on the X-ray picture, particularly very small white flecks caused by small deposits of calcium within the cancerous tissue.
When barium is swallowed (barium swallow or meal) or inserted into the bowel via the rectum (barium enema), it shows up densely white on the X-ray, outlining the inner surface of the oesophagus, stomach or bowel. Normally the lining appears smooth but the presence of a cancer can cause it to appear irregular or bulge inwards.

Sometimes other types of ‘dye’ or ‘contrast medium’ showing up white on an X-ray or scan are injected into the bloodstream via a vein. For example, the blood may carry the dye to the kidney which then excretes it into the urine. X-rays taken of the kidney and bladder (intravenous urogram [IVU] or pyelogram [IVP]) can then show up these organs quite clearly and an abnormal appearance may suggest that a cancer is present.
You may need to have one of the various forms of scanning as part of the process of diagnosing cancer or assessing its extent. Computed tomography (CT) and magnetic resonance imaging (MRI) scans involve you having to lie still in what is usually a large doughnut shaped structure. It will all be explained to you beforehand. CT scanning is now usually very quick.

MRI scanning takes somewhat longer, perhaps 15 to 20 minutes. These scanners can produce very impressive pictures of cross-sections or ‘slices’ of the part of the body being investigated, and they usually show growths much more clearly than simple X-rays. You may have to swallow or have an injection of a ‘contrast medium’ which will make the tumour or the nearby tissues show more clearly.

Ultrasound scanning involves moving a probe over the skin overlying the relevant part of the body or, occasionally, inserting a probe into the rectum, vagina or oesophagus. Images are produced on a screen by detecting very high-frequency, inaudible, ‘sound’ waves reflected off the internal tissues.

Isotope scanning is the creation of a picture by a ‘gamma camera’ which detects gamma rays emitted from the body after you have been injected with or swallowed a radioactive substance called an isotope. The most common type of isotope scan performed for cancer patients is a bone scan. The injected isotope is carried around the body by the bloodstream, but it tends to home in or ‘concentrate’ in any areas of bone where there is an attempt at healing any damage, which may have been caused by a tumour that has spread from another part of the body. The high concentration of isotope at such sites results in their appearance as ‘hot spots’ on the gamma camera picture of the skeleton. Interpre­tation can sometimes be difficult, however, and hot spots can often be caused by things other than cancer, such as degenerative disease (‘wear and tear’).

The value of another type of scanning, positron emission tomography (PET), in the assessment of cancer patients, is becoming increasingly recognised. This can sometimes detect tumours that are invisible on other types of scans. It takes advantage of the tendency for special sugars injected into the bloodstream to be ‘taken up’ or absorbed by cancer cells much more rapidly than by normal cells. The sugar molecules have ‘radioactive labels’ attached to them, resulting in the cancerous tissue ‘lighting up’ on the scan pictures.
As well as being used in the initial assessment of people suspected of or diagnosed as having cancer, X-rays and scans are used also to investigate symptoms which might possibly be caused by a recurrence in someone who has been treated for cancer in the past. However, it is important to realise that scans are not foolproof: even the most sensitive ones may fail to pick up a very small cancer and they quite often show suspicious abnormalities that turn out to be completely benign.

Tumour staging

Once a biopsy has confirmed the presence of a cancer, it is common for it to be allocated to a certain ‘stage’. This describes the size of the cancer and indicates whether or not there is evidence that it has invaded adjacent tissues or has spread via the lymphatic vessels to the lymph glands, or through the bloodstream to more distant sites.
Various staging systems are in use but ‘TNM’ staging is the most widespread. ‘T’ refers to the primary tumour, ‘N’ to the lymph nodes and ‘M’ to distant spread (metastasis). A number is allocated to each letter. For example, a woman with a breast cancer three centimetres in diameter which has affected some of the lymph nodes in her armpit, but who does not have any evidence of more distant spread, could be said to have a ‘T2N1M0’ tumour. Here ‘T2’ indicates a primary tumour between two and five centimetres in diameter, ‘N1’ denotes involved but removable lymph nodes confined to the armpit, and ‘M0’ indicates that there has been no detectable distant spread.
Staging can be helpful in estimating prognosis, making recommendations for treatment, and in assessing and comparing the results from treatment.