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

Evidence summary Level References
For men with metastatic disease:
orchidectomy and LHRH agonist have similar effects on overall
survival
medical or surgical castration appear to provide a survival
benefit when compared with anti-androgen (steroidal or non
non-steroidal) monotherapy.
Recommendation
I & II 1-5
Patients with metastatic prostate cancer can be treated with either orchidectomy or LHRH
agonist based on patient preference. Anti-androgen monotherapy should be avoided as
the data indicate this is probably associated with a shorter overall survival.
Grade C
5.1.2 Single agent versus total androgen blockade
Castration therapies are effective but temporary therapies for metastatic disease, but are justifiable in
context of preventing potential androgen “flare” to avoid further impingement if there were other
areas of metastatic disease that may already be causing significant but not clinical evidence of cord
compression. Numerous RCTs have examined whether combined androgen blockade (CAB) might
provide a survival benefit when compared with castration monotherapies in the treatment of
metastatic (M1) prostate cancer. Most of these trials have been the subject of three meta-analyses 6-8 ,
with the largest of these 8 following up all 8275 participants in 27 RCTs.
There is some heterogeneity in study design in this extensive body of literature, It includes some trials
using steroidal anti-androgens and others using non-steroidal anti-androgens in combination with
orchidectomy or LHRH agonist. Another source of heterogeneity was the inclusion in some studies of
patients with locally advanced disease (M0) along with patients with radiographic evidence of disease
(M1). However, over 80% of men included in the largest meta-analyses had metastatic disease.
The overall results of the meta-analyses demonstrate either no significant benefit 8 or only a small
benefit 7 when results for both steroidal and non-steroidal anti-androgens were combined. The
inconsistencies could be explained by the heterogeneous nature of the studies. More specifically,
however, the use of cyproterone acetate appears to be detrimental (the difference in mortality rates
was 2.8%) in the largest meta-analyses 8 whereas non-steroidal anti-androgens were associated with a
modest but significant improvement, with a difference in mortality rates of 2.9% 8 and an odds ratio
for overall survival of 1.29 at five years. 6
The number of patients who die of metastatic prostate cancer each year (second leading cause of male
cancer deaths) and the overall survival benefit indicates that these data are of significant clinical
relevance. The modest increase in overall survival, however, is balanced against the increased side
effects of adding a non-steroidal anti-androgen to androgen deprivation (castration) therapy and this
limits the clinical impact or usability of combined androgen blockade for all patients.
The data can be directly generalised to patients with metastatic prostate cancer as both LHRH agonists
and anti-androgens are on the PBS for this indication and orchidectomy is an easily accessible
procedure.
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Overt metastatic disease and/or loco-regional progressive disease