Locally advanced disease

taken from Small Gland, Big Problem 4th Edition
by Professor Roger Kirby, Health Press 2011

If your cancer has spread outside your prostate, but has not yet spread to the lymph nodes close by or to more distant locations, such as the bones, it is described as being ‘locally advanced’. (In the TNM staging system, this state is known as T3–N0–M0.) The treatment options for such disease are:

  • active surveillance or watchful waiting (for older, less fit men, as before)
  • hormone therapy
  • intermittent hormone therapy
  • hormone therapy followed by radical prostatectomy
  • hormone therapy followed by radiotherapy
  • anti-androgen alone (monotherapy).

Active surveillance

The rationale behind adopting the approach of active surveillance has been outlined earlier (see pages 37 and 38). However, it is important to realize that at this stage, because the cancer is more advanced, it is likely to cause symptoms and become life-threatening more quickly than a low-grade cancer that is still confined to the prostate. Active surveillance for locally advanced prostate cancer is therefore mainly applicable to older, less fit men with a shorter life expectancy.

Hormone therapy

Hormone therapy is sometimes called ‘cytoreduction’, and has been touched on in the previous section. There are several ways by which this can be achieved:

  • LHRH analogues, which block production of testosterone; LHRH is a naturally occurring hormone, and the ‘analogue’ part of the name means that this is a synthetic form with a structure similar to the natural form
  • antagonists, which block the production of testosterone
  • anti-androgens, which block the action of the male hormone testosterone in the body.

Testosterone, an androgen or male hormone, is produced in the testicles and has the effect of stimulating cancer growth. The aim of hormone therapy is to reduce the effect of testosterone by switching off testosterone production (the LHRH analogues or LHRH antagonist) and/or by dampening its effects on the cancer (the anti-androgens). The overall effect is that the tumour size is reduced and the progression of the tumour is delayed (hormone therapy does not offer a complete cure, however).

Usually, implants containing a LHRH analogue are inserted by injection at monthly, 3-monthly or even longer intervals. Your body may react to the first injection by initially increasing the amount of testosterone it makes – this is the so-called ‘flare’ effect. To counter this, you will probably be given an anti-androgen, such as Casodex (bicalutamide), to take a few days before and then continue for several weeks at the beginning of treatment with the LHRH analogue. The flare phenomenon does not occur with an LHRH antagonist.

Possible side effects. As a consequence of stopping the production of testosterone, men receiving an LHRH analogue lose their sex drive and are unable to achieve an erection. This is gradually reversed if the drug is stopped. Some men also experience hot flushes – these may be eased by low doses (50 mg/day) of Cyprostat (cyproterone acetate).

Anti-androgens may cause mild stomach upsets and diarrhoea. Rarely, they can have a harmful effect on your liver (so you will need regular blood tests while you are taking these tablets).

How effective is hormone therapy? Hormone therapy alone reduces the tumour size and slows the cancer progression in around 80% of men with locally advanced disease. It does not destroy all the cancer cells, so the cancer is not cured, but its progression is significantly delayed and the effects of other treatments, such as radiotherapy,
are enhanced.

Intermittent hormone therapy

Intermittent hormone therapy is a newer approach to hormone therapy. An LHRH analogue is given for about 36 weeks and then discontinued (providing the PSA level has dropped down to a normal value). When the PSA level returns to a predetermined level, the hormone treatment is started again. Some doctors believe that this might make the cancer cells susceptible to the drug for longer than they would be if treatment was continued without a break. Studies looking at the long-term safety and effectiveness of this approach are under way, but for the moment it is still experimental.

Hormone therapy followed by radical prostatectomy

Some doctors believe that shrinking the tumour with hormone therapy before carrying out a radical prostatectomy increases the chance of removing all the cancer. This approach has been tested in long-term studies. The latest data suggest, however, that there are no concrete long-term advantages to having hormone treatment before surgery,
so this approach is not generally recommended.

Hormone therapy followed by radiotherapy

Again, studies are being carried out to see whether hormone treatment before radiotherapy gives better results than radiotherapy alone. In this case, the results are encouraging, suggesting that the hormone treatment does indeed offer a benefit in terms of curing,
or at least delaying, the progress of disease. This is probably because the shrunken tumour is more susceptible to the anti-cancer effects of ionizing radiation. In men at higher risk, the hormone therapy is often continued for several years after the initial treatment.

Anti-androgen monotherapy

There is now scientific evidence that an anti-androgen drug alone (i.e. monotherapy) can also help to slow the progress of advanced cancer, particularly when bone metastases are not present. The advantage of this approach is that anti-androgens have less effect on sex drive and are less likely to cause erectile dysfunction than the long-acting injectable LHRH analogues. Breast tenderness and enlargement can occur but, although these side effects can be troublesome, they can usually be prevented by a short course of radiotherapy to the nipple areas. Liver function is only rarely disturbed by agents such as Casodex (bicalutamide), but blood testing should be performed to be sure. Worries in Scandinavia about cardiac side effects have not been borne out by studies in other countries, so this treatment is considered by doctors to be completely safe.