Clinical Practice Guidelines for the management of locally advanced ...

therapy since such studies would be unethical. ADT is an effective therapy for metastatic disease
(albeit temporarily) and patients can be salvaged at the time of symptomatic progression.
Evidence summary Level References
The limited data suggest patients with asymptomatic metastatic
prostate cancer are not advantaged by early androgen
deprivation therapy until symptomatic progression.
Recommendation
II 15, 16
Androgen deprivation therapy is indicated for metastatic prostate cancer. Immediate
therapy is warranted for symptomatic metastases. The evidence for immediate therapy for
asymptomatic metastases is unclear, but it is definitely warranted if delay may result in
complications (eg spinal cord compression from vertebral metastases).
Grade C
A decision about whether to defer therapy for patients with asymptomatic metastases will be a
discussion between patient and physician. Patients will require close follow-up if therapy is deferred.
Close evaluation would include an MRI of the spine for patients with documented but asymptomatic
vertebral metastases to ensure there is no pending spinal canal encroachment which would necessitate
more urgent treatment. 17
5.1.4 Toxicity
Numerous trials examining hormone therapy as a treatment for metastatic disease reported adverse
events and toxicities. Many included patients without clinical metastatic disease and as a result patient
populations were often markedly heterogeneous. Furthermore, the duration of follow-up ranged from
less than six months to many years and, in a number of studies, this was unclear. Finally, as with the
trials of ADT for non-metastatic disease, most of these RCTs had the limitations of focusing on
efficacy outcomes rather than toxicities with adverse events. The latter were rarely comprehensively
recorded and evaluated rigorously and so are potentially understated. A final concern is that many
studies were sponsored by the pharmaceutical industry and this may have introduced a bias.
Early versus delayed androgen deprivation
There were three RCTs comparing immediate castration with delayed treatment that included patients
with metastatic disease. Two of these studies included patients with M0 disease and the third was a
M1 subgroup analysis. Two examined cardiovascular mortality and one examined haemoglobin
levels. Castration did not significantly increase cardiovascular mortality 15, 16, 18 , however it did cause a
significant decrease in haemoglobin levels. 19
CAB versus monotherapy
As cyproterone acetate is not recommended for first-line ADT by the UK Committee on the Safety of
Medicines and in the ASCO Guidelines, this medication was not considered.
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Overt metastatic disease and/or loco-regional progressive disease