Prostate Cancer: Background
Prostate cancer develops as a result of a series of faults occurring in the genes that control cell growth in the prostate. A tumour is malignant (cancerous) when this genetic control breaks down and the cells are dividing in an unregulated manner. The cancer can spread beyond the prostate (a process known as metastasis) as cancer cells leave the tumour in the prostate and enter the bloodstream and lymphatic system. In this way, they reach other parts of the body (for example, the lymph nodes or bones) and secondary tumours develop.
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.
As the cancer develops from prostate cells, it is not surprising that early, less aggressive cancers bear a close resemblance to prostate tissue. As the cancer becomes more aggressive and dangerous, these similarities are progressively lost. This process is known as �de-differentiation� and was quantified in the 1960s by the pathologist Dr Gleason. The so-called �Gleason score� is a means of grading the cancer, and doctors can use this to estimate the likely outcome in their patients.
Once prostate cancer cells have developed the ability to invade tissue, they initially spread locally within the gland. Small tumours can only be detected by examining a sample (biopsy) of an apparently normal gland; larger cancers can usually be felt as a firm nodule on rectal examination by the doctor (the digital rectal examination or DRE).
Figure 3: Cancer development
Local invasion precedes distant spread, which can only occur when individual cancer cells have developed the ability to metastasise. Central to this process is the ability to acquire 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 new agents, such as angiostatin � provide a very promising new avenue of prostate cancer therapy.
Figure 4: Spread of prostate cancer
Risk factors
Your chance of getting prostate cancer depends on your risk factors; a risk factor predisposes you to a disease (a high level of cholesterol in the blood is, for example, a well-known risk factor for heart disease). The strongest risk factor for prostate cancer is increasing age. The disease rarely occurs in men under 40, but commonly affects men beyond middle age.
The next most important risk factor for prostate cancer is family history. Like breast cancer, prostate cancer runs in families and has been linked, so far, to two genes. Men whose father, brother, grandfather or uncle has had the disease have an increased risk of developing prostate cancer compared with a man 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. They seem to develop a more aggressive form of the disease and at a younger age than Caucasians. Men of Far-Eastern extraction seem to be relatively less affected by the disease.
A number of modifiable risk factors have been identified including a high level of animal fat in the diet. A man worried about his risk of prostate cancer (or indeed heart disease) is well advised to reduce his intake of eggs, milk, cheese and red meat. In addition, various dietary supplements may offer some protection. Preliminary studies suggest that both vitamin E and selenium may help. (If you want to take a vitamin or mineral supplement, it�s a good idea to check with your GP first; some ingredients can interfere with medicines that you might be taking or worsen a medical condition.)
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 helps the body to produce vitamin D.
Symptoms
Bladder outflow obstruction is the main symptom associated with prostate disease. Frequency, hesitancy, poor urinary flow and having to get up in the night a few times are all part of this problem. These symptoms do not identify prostate cancer. Other possibilities are benign enlargement of the prostate and prostatitis. Other symptoms of localised prostate cancer include blood in the urine, erectile dysfunction and pain local to the prostate area. More advanced local disease can cause incontinence, constipation or rectal bleeding.
More than 40% of men diagnosed as having prostate cancer still do not reach their GPs until they have metastatic disease. Pain resulting from bony metastases, particularly in the pelvis and lumbar spine is the major symptom. Other symptoms of distant metastases are sciatica, lymph node enlargement, swelling in the lower limbs. Widespread metastases may give rise to weight loss and lethargy.