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.
Epidemiology
Clinical Features
Investigations
Treatment