Prostate cancer > What is prostate cancer and what causes it?
Prostate cancer develops as a result of a progressive series of faults occurring in the genes that control cell growth in the prostate. These faults can be inherited or develop as a result of damage to the DNA, the material that controls the function of the cell, caused by dietary components, cancer-inducing chemicals or radiation. Normally, cells divide only when the body needs them to, and the process is under strict genetic control. When this genetic control breaks down and the cells begin dividing in an unregulated manner, a mass of excess cells forms (a tumour). A tumour can be benign or malignant, depending on its capacity to invade healthy surrounding tissue (if it can invade, it is cancerous). Because of its capacity to invade surrounding areas, cancer can spread to sites around the prostate, in which case it is said to be locally advanced. It can also spread to distant sites in a process known as metastasis, which occurs as the cancer becomes more advanced. Cancer cells can break off from the tumour in the prostate and enter the bloodstream and lymphatic system (the latter is a network of tiny vessels that drain fluid from all the organs in the body). In this way, cancer cells are transported to other parts of the body (for example, the lymph nodes or bones) and, like seeds growing in fertile soil, secondary tumours develop.
Stages of cancer
The earliest stage in uncontrolled cell growth is not actual malignancy, but pre-malignancy, known as prostatic intraepithelial neoplasia (PIN for short). PIN is characterized by a ‘heaping up’ of cells within the prostate, but there is no invasion of healthy tissue at this stage. With time, however, these dividing cells may develop the ability to invade and occupy the prostate tissue. Such early signs of invasion give the pathologist examining a sample (biopsy) of prostate tissue under a microscope the clue that actual cancer has developed from the pre-malignant PIN changes. At this stage, the level of a substance known as PSA in the blood usually begins to rise – another clue that invasive prostate cancer is developing.
| As prostate cancer develops, it forms a nodule that can then grow and spread to the seminal vesicles and other local structures. |
As cancer develops from prostate cells, when looked at under the microscope, early, less aggressive cancers bear a close resemblance to normal tissue. As the cancer becomes more aggressive and potentially dangerous, these similarities are progressively lost. This process is known as ‘de-differentiation’ and was described in the 1960s by the pathologist Dr Gleason. A sample of prostate tissue is given a ‘Gleason grade’ according to the shape, size and structure of the cells in the sample. The grading runs from 1 to 5; the higher the number, the more aggressive the cancer. Because the cells will not appear uniform across the tissue sample, the two most prominent regions are usually assessed, and the two grades added together to give what is known as the ‘Gleason score’. Doctors can use this to estimate the likely outcome for their patients. The higher the score (from 2–10), the more potentially dangerous the cancer in terms of progression.
Once prostate cancer cells have developed the ability to invade tissue, they initially spread locally within the gland and then start to invade the capsule that surrounds the gland. Small tumours can be detected only by examining a biopsy of an apparently normal gland under the microscope; larger cancers can usually be felt by the doctor as a firm nodule during an examination via the back passage (rectum), known as the digital rectal examination.
| As the cancer becomes more advanced, the cells are able to break off from what is known as the primary tumour. These cells enter the blood or lymphatic system and are transported to distant parts of the body. Once deposited at a site, the cancer cells start to grow and multiply, and secondary cancers called metastases are formed. |
At first, the cancer spreads locally to tissues around the prostate, such as the seminal vesicles. Eventually, however, it can spread to more distant sites, such as the bones. The mechanisms by which cancer cells acquire the life-threatening ability to spread (metastasise) are currently the subject of intense scrutiny. Central to the process is the ability to obtain a new blood supply to provide oxygen and nutrients to the cancer cells so that they can grow (all cells have these requirements). The development of a new blood supply has been termed ‘angiogenesis’, and angiogenesis inhibitors, which include the infamous drug thalidomide, as well as newer agents such as angiostatin, provide a very promising new avenue of treatment for prostate cancer; as yet, however, none of these have been approved for clinical use.
Why do some men get prostate cancer and others do not?
Overall, the lifetime risk of a man developing prostate cancer is now around 10%. Your chance of getting prostate cancer depends on your personal risk factors. A risk factor is something that makes you more likely to develop a certain disease; for example, a high cholesterol level in the blood is a well-known risk factor for heart disease.
| Risk factors for prostate cancer |
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The strongest risk factor for prostate cancer is increasing age. The disease rarely occurs in men under 40, but commonly affects men beyond this age. The average loss of life expectancy is about 9 years – precious retirement years for which most men have been working and eagerly anticipating all their lives.
| Older men are more at risk of developing prostate cancer than their younger counterparts. |
The next most important risk factor for prostate cancer after age is family history. Like breast cancer, prostate cancer runs in certain families and has been linked to a number of genes. A man whose father, brother, grandfather or uncle has had the disease has an increased risk of developing prostate cancer compared with one without an affected relative. This is particularly the case if the disease developed in the close relative when he was under 60.
Race is also a factor, with men of Afro-Caribbean extraction being at highest risk. These men seem to develop a more aggressive form of the disease and at a younger age than Caucasians. Men of Far Eastern descent seem to be relatively less likely to be affected by the disease.
Can prostate cancer be prevented?
Clearly you cannot change your age, ancestry or race (these are ‘non-modifiable risk factors’). However, several other risk factors for prostate cancer have been identified over which you can have some influence – lifestyle factors, such as diet and exercise. In addition, various dietary supplements may offer some protection.
Geographically, prostate cancer tends to become more common as you move away from the equator; Norway and Sweden have the highest death rates from the disease worldwide. This fact points us to two further possible modifiable risk factors – low vitamin D and low exposure to sunlight, which itself helps the body to produce vitamin D. This evidence provides a good excuse for regular holidays in the sun!
As already mentioned, prostate cancer is characterized by an abnormal overgrowth of prostate cells. As scientists unravel the steps involved in the development of this abnormal cell overgrowth, it is possible, and indeed probable, that we will one day be able to intervene to reverse the earliest phases of the disease. A number of compounds that have this potential are currently being investigated for effectiveness and safety. One of the problems is that it is considerably more difficult (and expensive) to demonstrate that a given drug or vitamin is capable of preventing a disease than it is to show that it can cure a specific problem once it has developed. Because we are never sure exactly who will develop a disease such as prostate cancer, very large numbers of individuals have to be studied for many years (5, 10 or even 15) before we can be certain that a drug can safely and effectively prevent the disease from occurring.
The drug Proscar (finasteride) has been evaluated for its preventative activity. A recent report has revealed that 25% fewer cases of prostate cancer occurred in the men treated with Proscar at a dose of 5 mg/day. Surprisingly though, those cancers that did occur appeared to be more aggressive in nature than those that occurred in the men not treated with Proscar. For this reason, Proscar has not been approved for use as a preventative agent. Another large study, known as REDUCE, is currently looking at a medication that acts in a similar fashion to Proscar, namely Avodart (dutasteride); however, the results are not expected for some time. Recently, reports have begun to appear suggesting that the cholesterol–lowering drugs known as statins, such as Lipitor (atorvastatin), may offer some protection against prostate cancer. This is intriguing, but needs to be verified.
Other so-called chemopreventative agents will doubtless emerge as more research is undertaken.