Prostate Cancer

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Metastatic prostate cancer is a common condition encountered in palliative medicine. It frequently causes painful bony metastases and recurrent anaemia due to a combination of chronic disease and bone marrow infiltration. Occasionally bleeding from thrombocytopaenia is also an issue, as is, spinal cord compression, hypercalcaemia and obstructive uropathy.

Epidemiology

Most patients with metastatic prostate cancer have had previous local disease and are discovered to have metastases when either a rising PSA is discovered or bone pain (especially in the back) develops. A smaller proportion of patients are found to have metastatic disease at diagnosis.

Clinical Features

Fatigue and widespread bony pain are the most common clinical features of progresive metastatic prostate cancer. As the disease progresses, mild confusion is also relatively common although the cause is not always clear.

Occasionally recurrent haematuria is very problematic and significant amounts of bleeding can cause anaemia as well as bladder outlet obstruction through the formation of bladder and urethral blood clots.

Investigations

Markers of progressive disease include:

  • A rising PSA
  • A rising ALP
  • Hypercalcaemia
  • Worsening anaemia or pancytopaenia and a leuocoerythroblastic blood film
  • A dropping albumin

Treatment

Hormone and chemotherapy

Patients with metastatic prostate cancer often receive treatment sequentially, initially starting with androgen-deprivation treatments (e.g. surgical orichidectomy, anti-androgens such as flutamide or bicalutamide or GnRH agonists such as leuprolide, goserelin, buserelin or triptorelin). In patients with high volume metastatic disease, docetaxel is often given in addition to androgen-deprivation therapy.

When progression of disease (e.g. a rising PSA) ocurs whilst a patient is receiving androgen-depreviation treatment, abiraterone and enzalutamide have both been shown to prolong survival. Abiraterone blocks production of androgens in the tumour and in the testis and adrenals. It is given in conjunction with prednisolone. Enzalutamide blocks the androgen receptor.

Symptomatic measures

Analgesia and Radiotherapy

Widespread pain due to bony metastases is treated in the usual way (e.g. with opioids, steroids, NSAIDs). Radiotherapy is often very helpful for single bony metastases and is the usual treatment for spinal cord compresion.

A single fraction of radiotherapy is given for painful bone metastases providing complete analgesia in about 50% of patients and some analgesia in about 30% of patients.

Prophylactic pinning to prevent fractures

In cases of painful metastases to long bones such as the femur, it is important to consider the fracture risk. In general, fracture risk is less in cancers such as prostate cancer which tend to cause osteoblastic lesions when compared with cancers like multiple myeloma which tend to cause osteolytic lesions. However, severe pain in a long bone with an associated large tumour deposit visible on a plain film is an indication for seeking an orthopaedic opinion on the value of prophylactic pinning. A system known as Mirel's Score is sometimes used to quantify fracture risk.

Bisphosphonates and Denosumab

Bisphosphonates and denosumab are known to reduce pain in men with bony metastases as well as reduce incidence of pathological fractures.

Zolendronic acid is a bisphonate that is given monthly. The usual dose is 4mg via IV infusion over 20 minutes, but a dose reduction is required in renal failure.

Denosumab is a relatively new agent. It is a monoclonal antibody that binds to RANK ligand. It appears to be slightly more effective than zolendronic acid at preventing fractures but does not improve survival.

Osteonecrosis of the jaw is a serious complication of both denosumab and zolendronic acid and occurs in about 2% of patients receiving the treatment. Hypocalcaemia occurs in about 10% of patients. Both these adverse effects are slightly more common for denosumab than for zolendronic acid.

Fatigue

Transfusions often help with symptomatic anaemia, although in most cases energy loss is multi-factorial in aetiology. It may be worth trying a transfusion if the haemoglobin is 80 or less, however, if the transfusion brings about no improvement then this is indicative that the anaemia is the not the primary cause of fatigue.

Steroids (e.g. dexamethasone 2mg daily) may improve energy levels although this is often short-lived.

Treatment of haematuria and urinary retention

Fatigue due to anaemia from recurrent haematuria can be treated with transfusions. Tranexamic acid may reduce bleeding. Palliative radiotherapy may also reduce bleeding.

Occasionally significant amounts of bleeding occur resulting in clot retention and urinary retention. This is very uncomfortable and needs treatment with insertion of a 3-way urinary catheter and bladder wash-outs. It is worthwhile getting an urgent urology opinion in these cases as there may be a role for cystoscopy.

Prognosis

The median survival of men with hormone resistant prostate cancer and bony metastases is about 12 months.

Authors

Graham Llewellyn Grove