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5. When is hormone treatment used?

Hormone treatment is normally used for men whose cancer has not been cured by surgery or radiotherapy. The timing of hormone treatment in response to a rising PSA level varies. It is based to some extent on the speed of tumour growth and its location.

Hormone treatment is the principal therapy for metastatic prostate cancer – when the prostate cancer cells have escaped from the prostate to grow in other sites of the body. The treatment may be started soon after this diagnosis is made. On occasions a delay in starting does not pose serious risk to the patient.

Hormone treatment may also be used to shrink a tumour before or together with radiotherapy. There is evidence that this hormone therapy is beneficial when used with external beam radiotherapy as a treatment for high risk localised prostate cancers. Once the radiotherapy is complete, the hormone treatment may continue for months to several years. PSA tests are used to check on the tumour control.

4. Monitoring after radiotherapy to the prostate

After radiotherapy (external beam radiotherapy and/or brachytherapy), the PSA ought to drop to low levels and remain low. The time taken for this fall is different from that following surgery, since the prostate gland remains in the body and PSA is produced by both normal and cancer cells. The lowest PSA reading (called the nadir) may not occur for up to 18 months following radiotherapy. Ideally the PSA ought to fall to below 1.0 ng/mL; at this level, the outlook for cancer control is very good.

Up to one-third of men who have had brachytherapy will have a temporary rise in PSA during the first 12–24 months. After this, the PSA will resume falling. This is referred to as PSA bounce. The cause of PSA bounce is not well understood. It can raise concern about cancer growth for patient and doctor, but patience, with continued 3-monthly PSA testing, is usually the best strategy.

The frequency of measuring the PSA after radiotherapy is somewhat controversial. Many specialists would recommend once every 3–6 months for the first 2 years, 6 monthly for 2–5 years and annually thereafter.

3. Learning that it’s Cancer

Hearing the word cancer is usually a shock. Men often say that after that word was mentioned, they felt in a daze: ‘Didn’t hear anything the doctor said’. A man’s response to a diagnosis of cancer may be shaped by the experience of a father, uncle or friend who was diagnosed some time ago, before current improvements in knowledge and treatment. It is good to remember that our success with treating cancers, including prostate cancer, has steadily improved over time. Nevertheless, there is a lot to take in.

The following suggestions may be helpful at this stage:

  • Take your time. Prostate cancer is normally slow growing. Most men have time to talk to others and think things through before making a decision.
  • Talk to your GP, who may answer some of your questions and may be helpful in clarifying information about the disease and treatments.
  • Make a second appointment with your urologist – write a few questions down before the appointment as a reminder, or have someone come with you.
  • A second opinion can be arranged through your GP or specialist. Men with localised cancer are often encouraged to talk to a second urologist (surgeon) or a radiation oncologist (a doctor who specialises in radiotherapy for the treatment of cancer).
  • Talking to other men with prostate cancer can be helpful in learning about the experience of treatment and life after diagnosis. This can be arranged through the Cancer Council Helpline or a support group (see Resources).
  • Partners of men with prostate cancer also feel shock and distress at a diagnosis of prostate cancer. Men and women look for support in different ways, and often have different concerns.

2. Key Points

  • The PSA test is used as a guide to estimate the risk that cancer is present or is likely to develop in the future. It is not always accurate when used in this way and many men with high PSA levels do not have cancer.
  • PSA is of particular use after prostate cancer diagnosis, when it can be an indicator of how far the cancer has grown (stage) and for monitoring the success of treatment.
  • PSA is also used together with other clinical measures such as tumour grade (Gleason score) to assess the risk posed by a particular cancer, and so the type of treatments that might be needed and their likely outcome.

4. What if the PSA starts to rise again after surgery?

If the PSA remains detectable or starts to rise after a radical prostatectomy, there must be prostate cells producing it. This is almost always the first sign of a persistent or returning cancer. If the PSA becomes detectable the doctor may repeat the test to confirm the level and may monitor the PSA for many months before recommending a treatment. The treatment decision depends on where the likely site(s) of the cancer recurrence is.

One possibility is that the cancer cells remain only in the pelvic region (in the area close to where the prostate was). The tissue removed during surgery, for example, may show that the cancer extends to the cut edge (positive surgical margin), suggesting that some cells may remain in that area. Radiotherapy may be offered immediately after surgery (adjuvant radiotherapy) if the results suggest some cancer remains in the operation site. This may be the case if there is a positive surgical margin, the cancer has spread just outside the prostate (called locally advanced) or the cancer is high grade (Gleason score 8–10).

A bone scan, CT scan or MRI investigation can help to determine if the cancer has spread to other parts of the body. However it is not as useful in men with a PSA only just starting to rise. This is because the amount of cancer is still small and these tests cannot locate small amounts of cancer.

If cancer is identified in the pelvic area and not elsewhere in the body, radiotherapy can be used to treat it. This is called salvage radiotherapy. It has a mild to moderate chance of curing the cancer. Salvage radiotherapy after surgery is most effective if given when the PSA is still low (less than 0.5 ng/mL).

If the PSA continues to rise and the cancer has spread beyond the prostate area, the most common treatment is hormone treatment (removal of male hormone activity), since most prostate cancer cells need male hormone to grow.

There is debate about the best time to start hormone treatment. Many urologists suggest starting before the PSA climbs above 15 ng/mL. This decision depends on the rate at which the PSA is rising and how the man feels about the side effects of this treatment (see Mr PHIP No. 5).

4. Can doctors tell me the likelihood of cancer recurring?

If your main treatment was radical prostatectomy (surgery to remove the prostate and surrounding tissues), a specialist doctor (a pathologist) will examine the prostate gland and tissue that was removed. The extent and appearance of the cancer cells give more information about the risk of return (or recurrence) of the cancer. Should the cancer be confined to the prostate gland, the outlook is better than if it has spread outside the ‘capsule’ of the prostate or into the attached seminal vesicles, which are removed with the prostate.

The pathologist will see whether the cancer extends to the cut edge of the prostate (the surgical margin). If this is so, it is likely that some cancer cells have been left behind. This is called a positive surgical margin. In this case, your doctor may recommend you have some extra treatment within a few months following your operation, such as external beam radiotherapy. The cancer grade or Gleason score gives an idea of how aggressive the cancer is.

5. What does hormone treatment involve?

There are two ways of reducing male hormones:
• by surgery, where the testicles are removed (orchidectomy)
• by medication, either in the form of regular injections and/or tablets.

Both are effective.

Surgery (orchidectomy)

The testicles provide over 95% of the male hormones and so surgery to remove the testicles reduces the blood hormone levels. This occurs very quickly after the operation.

An advantage of surgery is that the inconvenience and cost of regular medications is avoided.
The operation is usually done as day surgery. The scrotum (pouch of skin that holds the testes) remains and the testes are removed through a small incision. The operation, called an orchidectomy, is permanent.

Medication

Medications are available as an alternative to orchidectomy. Some are injected and others taken as tablets.

Injectable drugs act on the brain to reduce the production of male hormones in the testicles. They currently last from 1–6 months per injection. This means that regular monthly or 6-monthly injections are required to control the cancer cell growth. Should these be stopped in men with metastatic cancer, the cancer will start to grow again when male hormone levels begin to rise (after several months).

Drugs given as tablets are called anti-androgens. They block the action of the male hormone in the reproductive organs and are not as effective as injectables in controlling cancer growth. Treatment with both injectables and tablets is called combined androgen blockade. Sometimes doctors start with a tablet, then 2–4 weeks later give an injectable medication. This is to control a brief increase in testosterone activity (called ‘flare’), which passes with time.

The effectiveness of hormone treatment can be checked with a blood test for testosterone. Its effectiveness in controlling the cancer can be checked with a PSA blood test (see Mr PHIP No. 1 and 2), although this is not always reliable.

Sometimes hormone treatment may be given in cycles (i.e. started and stopped repeatedly). This type of treatment is called intermittent hormone treatment. Typically, the treatment is continued for several months until the PSA has reached a low level, then the hormone treatment is stopped.

The PSA then gradually rises. Once it rises to a particular level (and this can take many months), hormone treatment is restarted. The main benefit of this approach is reduced side effects (see the next section) without a significant reduction in tumour control. Trials suggest that cancer control is similar with both continuous and intermittent therapies.

4. How is cancer recurrence detected?

The best indicator of recurrence is the prostate specific antigen (PSA) blood test. PSA is a protein produced by normal prostate and prostate cancer cells. It is found in the blood in higher amounts than normal when cancer is present (see Mr PHIP No. 2). It is a very good indicator of whether living cancer cells remain following surgery or radiotherapy. The meaning of the test result differs depending on which treatment you had.

Monitoring after surgery

Since PSA is produced by both normal and cancer cells in the prostate, if all prostate cells have been removed at the operation, then the level of PSA ought to fall to an undetectable level, or less than 0.1 ng/mL. The time taken for the PSA to drop to this level after surgery depends on how high it was before the operation; in most cases, it should be undetectable at 3 months after surgery.

Most surgeons recommend a PSA test every 3–4 months after surgery for the first 2 years and then 4–6 monthly for 2–5 years. After this, the risk of the prostate cancer returning is small. Annual testing is often then recommended.

Your doctor may suggest a different testing program. It depends on the nature of your cancer (see Mr PHIP No. 3).

4. What if the PSA starts to rise again after radiotherapy?

If the PSA rises and continues to rise, this normally indicates a return of the cancer.
On rare occasions, the rise may be due to growth of benign prostate cells, inflammation or infection within the prostate. Other non-cancer treatments may be appropriate.
The way the PSA changes is important. A steady continued increase is likely to prompt the doctor to suggest further treatment to control the cancer (often hormone treatment). Tests to try to identify where the prostate cancer cells are in the body may not be helpful until the PSA is over 20 ng/mL, because the scans do not pick up small groups of cells.

2. PSA – what is it and what causes it to rise?

Prostate specific antigen (PSA) is a protein in men that is secreted into ejaculate fluid by the healthy prostate. One of its functions is to aid sperm movement. Normally, only very low levels of PSA are able to enter the bloodstream. However, several conditions of the prostate can cause the PSA levels in the blood to rise. These include benign prostate enlargement, infection of the prostate and prostate cancer.

Benign enlargement of the prostate due to a condition called benign prostatic hyperplasia (BPH) occurs in older men and often causes urinary symptoms such as slow urine flow or stopping and starting urination. Because there are more prostate cells to produce PSA, the levels rise and this increases with age. For this reason, age-based thresholds (Table 1) can be used to decide if a test result is abnormal. The percentage free to total PSA ratio (described below) also helps to show whether raised PSA is due to benign enlargement. Benign enlargement does not ‘turn into’ prostate cancer.

A temporary rise in the PSA can be caused by a number of conditions: urinary infection, prostatitis (inflammation of the prostate) or a biopsy of the prostate. They can cause large rises. Small rises can be caused by ejaculation and even bicycle riding. Because of these non-cancer causes of PSA rises, it is not surprising that if you have an abnormally high test result, it is not always due to prostate cancer. The chance that you have prostate cancer given an abnormal PSA result is only about 1 in 3. If, in addition to the PSA test, you have a digital rectal examination, and it also is abnormal, your chances of having prostate cancer are greater (1 in 2).