4urology

Position of the prostate

The prostate is a walnut-sized gland which is located between the pubic bone and rectum. It wraps around the urethra, the tube that carries urine from the bladder.

One of the functions of the prostate is to produce and transport prostatic fluid. During an orgasm this fluid mixes with sperm and is ejaculated out of the penis.

Prostate cancer, which develops from cells in the prostate gland, is the second most common cancer in men in the developed world and the most common cancer in men in the UK. It is therefore a major cause of male death in the UK.

The disease grows very slowly in most cases. In fact, 89 percent of patients diagnosed with prostate cancer have a five-year survival rate, and 63 percent live at least 10 years after the disease is found and treated.

Eventually, the cancer may spread outside the prostate gland to other parts of the body. Since lymphatic vessels of the prostate lead to pelvic lymph nodes, cancer cells can spread out along these vessels, where they can reach lymph nodes and continue to grow.
 

Until recently the only risk factors associated with prostate cancer were age, race and family history. However, other factors have now been implicated, although their actual risk remains inconclusive.

Age

The primary risk factor is age. Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. However, many men never know they have prostate cancer and die of other causes. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s.

Race

Prostate cancer has a genetic component being more common in Afro-Caribbeans whoi also seem to get the more aggressive forms of the disease. It is very uncommon in people of oriental origin, however when oriental men (such as Japanese men) immigrate to the western world their incidence of prostate cancer increases, although it still remains lower than American caucasians and African-Americans. This suggests that there are other environmental factors such as diet that could be having an effect on risk.

Family history

A family history of prostate cancer increases the risk of having prostate cancer. The risk being approximately 3 times greater for men who have a first-degree relative such as a father or brother with prostate cancer, than it is for men without a family history. The more affected relatives a man has and particularly if their relatives were affected when they were young, then the more likely they are to develop the disease. There is currently no genetic test available for prostate cancer.

Diet

Several studies have shown benefits from diets high in vitamins D and E, vitamin A from plant sources and selenium from cereals or nuts (brazil nuts are high in selenium). Lycopene from tomatoes, most of this is in the skin of the tomatoe and stewed tomatoes found in tomatoe sauces have the highest levels. Omega-3 fatty acids from fish oils also appear to have a protective effect. However a diet high in animal fat appears to increase the risk of developing prostate cancer.

Smoking

There is an association between smoking and the risk of dying from prostate cancer rather than the incidence of the disease itself. It is not clear whether this is because smokers are more likely to put off seeking medical intervention early or it may be that smoking increases the aggressiveness of the disease.

Over the last 30 years prostate cancer rates in the UK have nearly tripled. Much of this increase is due to better detection through the widespread use of the PSA test.

Prostate specific antigen (PSA) is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer but it is also elevated in other prostate disorders. PSA levels can be also increased by prostate infection, irritation, benign prostatic hyperplasia (BPH), and recent ejaculation, producing a false positive result. Digital rectal examination (DRE) has also been shown in several studies to produce an increase in PSA. The effectiveness of the PSA test has therefore been questioned.

Arguments for testing

• If the result of the PSA test is favourable this will calm down my worries;
• The PSA test can help to find prostate cancer at an early stage and before it leads to complaints;
• If as a result of a positive PSA test I undergo successful treatment I may have a better chance of cure and may live longer;
• If the treatment is successful in an early stage, I may be spared the late symptoms of prostate cancer such as spread of the tumour to other parts of my body (metastases).
• I may miss the chance of cure and of avoiding prostate cancer death.
• Screening has been shown to lower prostate cancer mortality by 20 – 27% in men age 55 – 69. (However, more recent larger studies have given conflicting evidence on the ability of screening to reduce mortality.

Arguments against

• If my PSA value is elevated and further study does not show prostate cancer I will have undergone medical testing for nothing and this will have caused unnecessary anxiety;
• The PSA test can miss prostate cancer. After a normal result I may feel relieved for no good reason or may still remain worried;
• An elevated PSA test may detect a slow growing tumour which would otherwise never have given me any trouble;
• I may be confronted with the possible complications of the treatment of prostate cancer.

With an increase in PSA screening most cancers found are in a curable stage. Many of these cancers are not deadly and can be managed with a high rate of success. In many cases immediate treatment is not necessary but it is then necessary that you are followed up closely.

The results from two of the largest randomized trials regarding the efficacy of screening have now been published one from America dn the other from Europe. In the American trial (PLCO screening trial) the death rate from prostate cancer was actually higher in the group that had total screening compared to the control group that had only normal rates of screening. The other European study showed some benefit from screening, but the reduction in deaths was minor compared to the level of intervention needed to prevent it.

In this European Randomized Study of Screening for Prostate Cancer initiated in the early 1990s, the intention was to evaluate the effect of screening with prostate-specific antigen (PSA) testing on death rates from prostate cancer. The trial involved 182,000 men between the ages of 50 and 74 years in seven European countries randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. During a median follow-up of almost 9 years, the cumulative detected incidence of prostate cancer was 820 per 10,000 in the screening group and 480 per 10,000 in the control group. Deaths from these cancers in this time was much lower. There were 214 prostate cancer deaths in the screening group and 326 in the control group, a difference of 71 men per 10,000 in the tested group compared to the control. The researchers concluded that PSA-based screening did reduce the rate of death from prostate cancer by 20%, but that this was associated with a high risk of overdiagnosis, which means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent just one death from prostate cancer.

Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine checkup. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia. These include frequent urination, increased urination at night, difficulty starting and maintaining a steady stream of urine, blood in the urine, and painful urination. Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.

Rarely patients present with symptoms of advanced prostate cancer. Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and faecal incontinence.

When a man has symptoms of prostate cancer, or a screening test indicates an increased risk for cancer, he will be seen by a urologist who will first discuss the findings to date and do an examination including a digital rectal examination. This involves putting a finger in the rectum to examine the prostate for abnormal shape or nodules on the surface or to see if it is tender.

Digital rectal examination

The only test that can fully confirm the diagnosis of prostate cancer is a prostatic biopsy, the removal of small pieces of the prostate for microscopic examination. However, prior to a biopsy, several other tools may be used to gather more information about the prostate and the urinary tract. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.

Prostate biopsy

If cancer is suspected, a biopsy is offered. During a biopsy a urologist obtains tissue samples from the prostate via the rectum. A biopsy gun inserts and removes special hollow-core needles (usually five to eight on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. For more information on prostate biopsies please go to the treament section (link)

TRUS and biopsy

Gleason score

The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or Gleason score) of any cancer found. If cancer is found then it is graded according to the Gleason grading score. This grades prosate cancer from 1 to 5. It is now felt that grades 1 and 2 are variations of normal so cancer is graded from 3 to 5, with 5 being the most aggressive. There is often a range of grades within the one prostate so the disease is scored according to the 2 most common patterns present. This results in a score such as Gleason 3 + 4 with grade 3 being first as it is the most common pattern present and grade 4 the second most common. If a patient has prostate cancer of grade 3 only then their score would be Gleason 3+3 or an overall score of 6.

Gleason score

What does the grade of prostate cancer mean?

The grade of the cancer is the term used to describe how aggressive the disease is and whether it will progress quickly (months) or slowly (years). It is the combined score of the two commonest types of cancer seen under the microscope so ranges from Gleason score 6-10.

Least aggressive                  Gleason score 6

Moderately aggressive         Gleason score 7

Most aggressive                    Gleason score 8-10

Understanding the grading is of great importance for both the clinician and the patient as it will help determine which treatment options are available, as well as their likely success.

Once a diagnosis of prostate cancer has been made, it is important to confirm that the prostate cancer has not spread ouside of the prostate. If spread is suspected because of a high level of PSA, high grade of tumour or because of symptoms in the bones, a bone scan can be used to see if the the tumour has invaded the bone. This is a painless test, where a very small, harmless ammount of radioactive agent is injected into a vein. This makes its way to any cancer deposits within the skeleton and sticks to them if present. After a few hours, the patient is scanned by a special camera, similar to anx-ray machine, to detect these deposits if present.

Normal Bone scan

MRI and CT scans

Two other types of imaging are available, A magnetic resonance imaging (MRI) scan or a computerised tomogrphy (CT) scan. These imaging tests are sometimes used to obtain detailed images of the prostate and the surrounding tissues. The MRI uses magnetic fields and may not be suitable for all patients, the CT scan uses x-rays. Both are painless. These tests help the doctor to stage the prostate cancer.

MRI scan	CT scan

The stage of the prostate cancer refers to how far the cancer has spread. The classification commonly usedin the UK is shown below in a simplified form. (The prefix T is used by convention to identify the tumour stage, i.e. T1 or T2).

It is important to remember that although all prostate cancers have the potentil to progress, it can take years to move from Stage 1 to 4.

Prostate cancer staging

Stage 1   Earliest stage, where the cancer is so smll that it cannot be felt on digital rectal examination (DRE), but was discovered in a prostate biopsy or in prostate tissue that was surgically removed to 'unblock' the flow of urine by the prostate (as in transurethral resection of the prostate or TURP).

Stage 2   The tumour is now large enough to be felt on DRE, but it is still confined to the prostate gland and has not spread.

Stage 3   The tumour has spread outside the gland and may have invaded the seminal vesicles.

Stage 4   The tumour has spread to involve the surrounding tissues such as the bladder, rectum or muscles of the pelvis.