Metastatic disease

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

Once prostate cancer has spread to the lymph nodes and to distant sites, most frequently the bones, it is referred to as metastatic disease (the metastases are the secondary growths that occur at the distant site); in the TNM staging system, this state is known as T3–N1–M1. This is an advanced form of cancer, and one that is associated with a relatively poor outlook, but there is no need to give up hope, especially nowadays.

This stage of cancer can still be treated and progression of the disease can be delayed for several years. The treatment options are:

  • orchidectomy (surgical removal of both testicles)
  • hormone therapy with LHRH analogues
  • ‘maximal androgen blockade’, which is hormone therapy with a combination of LHRH analogue and anti-androgen.

Orchidectomy

Orchidectomy is a surgical procedure in which both the testicles
are removed. The reasoning behind this is that, as testosterone is produced in the testicles, their removal stops its production altogether. Most men (more than 80%) respond positively to this treatment, with the progression of their cancer slowing markedly for around 18 months and sometimes much longer.

The operation is straightforward and is performed under a local or general anaesthetic in around 30 minutes. The scrotal sac is opened and the testicles are snipped out. In selected patients, silicone testicular prostheses may be inserted to improve the cosmetic result. You may be allowed out of hospital on the same day, although often your surgeon will want you to stay in overnight to check for bruising. You must take things easy for a week or two, and you should also take regular baths or showers to keep the wound clean. Afterwards, the scrotum will look a little bruised, and later somewhat shrivelled and empty, unless prostheses have been used.

Although the operation seems rather drastic, and some men are concerned about ‘castration’ and the appearance of their scrotum afterwards, it is a one-off procedure and so avoids the need to take a prolonged course of hormone therapy. However, it is nowadays a rather uncommon way to treat prostate cancer as medical therapy is preferred.

Possible side effects and risks. As your body will be unable to produce testosterone after the operation, you will lose your sex drive and be unable to achieve an erection. You will also be infertile. These effects are irreversible, so consider the implications very carefully before consenting to an orchidectomy. Potential complications of the surgery are relatively few, but bruising, blood clots and infections do occur in some men. Hot flushes may result from the hormone changes in your body. You will not become ‘feminized’ or find that your voice changes, but you may notice that you lose some body hair and may have to shave rather less often. There is also often a change in skin texture and a theoretical risk of the brittle bone disorder known as osteoporosis.

Hormone therapy

LHRH analogues (see page 58) achieve the same result as removal of the testicles by blocking the production of the male hormone testosterone, and thus reducing the stimulation of cancer growth. LHRH analogues, such as Zoladex (goserelin), are usually administered as an implant, which is injected just under the skin of your abdomen. The procedure is repeated every month or 3 months. As with orchidectomy, a high proportion of men (more than 80%) respond to this treatment and the beneficial effects usually last for around 18–36 months. In terms of effectiveness and safety, there is little to choose between hormone therapy and orchidectomy, but most men prefer the former.

Possible side effects and risks. At first, the LHRH analogue actually increases testosterone production for a few days. Bone pain may increase as a consequence, and urinary symptoms may worsen. This is known as the ‘flare’ phenomenon. There is even a remote risk of the cancer causing pressure on the spinal cord and thus paralysis. To counter these effects, anti-androgens such as Casodex (bicalutamide) are usually given for 2 weeks before and then for the first 2–6 weeks of LHRH analogue treatment; these effectively block the effect of testosterone on the cancer. Use of the LHRH antagonist degarelix avoids the risk of flare and the need to use anti-androgens when starting treatment.

Maximal androgen blockade

Maximal androgen blockade combines the use of LHRH analogues with long-term anti-androgens. Whether or not this approach is superior to that using LHRH analogues only or orchidectomy is not entirely clear. Some studies show men respond for a longer length of time with this treatment, while others have failed to show such an effect. Many doctors do have confidence in this approach, though, and feel that it is particularly appropriate for younger, relatively fit men with advanced prostate cancer.

Possible side effects. As outlined previously, treatment with LHRH analogues results in a loss of sex drive and impotence. Hot flushes can also be a problem but sometimes respond to treatment with Cyprostat (50 mg/day). The other part of the treatment, anti-androgens, may upset your stomach and can sometimes cause diarrhoea.

Bisphosphonates

Since prostate cancer frequently spreads to the bone, a class of drugs known as bisphosphonates, which act to stabilize the skeleton and reduce bone loss, may be helpful. A study has demonstrated that Zometa (zoledronic acid) administered by intravenous infusion every 3 weeks can delay the development of skeletal problems, such as fracture, by up to 5 months. Side effects of this treatment are relatively minor; some patients develop a flu-like illness during the infusion but this is usually short-lived. Rarely, a problem with the jawbone can develop. More and more men with advanced prostate cancer are now being offered this treatment option, and studies are under way
to determine whether bisphosphonates may even prevent metastases in the bone developing in the first place.

Denosumab is a therapeutic antibody that targets a protein involved in bone ‘remodelling’, a naturally occurring process in which old bone is removed and new bone is added. By targetting the protein, denosumab reduces the removal of old bone and helps protect against bone-related problems in metastatic prostate cancer.