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

Evidence summary Level References
There appears to be a small but significant benefit from adding a
non-steroidal anti-androgen to androgen deprivation therapy. This is
a class effect in favour of non-steroidal anti-androgens. In contrast,
there appears to be a detrimental effect with the use of the
steroidal anti-androgens.
However, the benefit is modest and it required a large number of
clinical trials to come to this finding.
Recommendation
I & II 6-14
Patients with metastatic prostate cancer may be treated with a non-steroidal anti-androgen
combined with androgen deprivation therapy as a continuing strategy (beyond the period
of LHRH-induced surge [flare] of testosterone) if they are prepared to accept the greater
likelihood of unwanted effects from combination therapy.
It is recommended that patients with high–volume disease or disease where urgent tumour
debulking is required (eg impending spinal canal compression or urinary outflow obstruction)
be commenced on combined androgen blockade to prevent flare reactions. This required
period is approximately one month for an LHRH agonist and covers the time it takes for
testosterone levels to reach a castrate state. Continuation of combined therapy beyond
that period may be considered if the patient is prepared to accept the greater likelihood of
unwanted side effects from combination therapy.
Grade B
5.1.3 Early versus delayed androgen deprivation
One clinical scenario is the management of patients with radiographic evidence of disease without
symptoms. The question arises as to whether ADTs should be started immediately or delayed until the
onset of symptoms. Two RCTs have addressed this question. These trials took place in different eras.
One trial, VACURG-1, was performed in the 1960s and 1970s 15 , while the MRC Prostate Cancer
Working Group study was undertaken in the 1980s and 1990s. 16 This complicates the analysis
because of:
issues of stage migration and stage detection with pre bone scan and pre PSA era incorporated
with studies of patients who are more accurately staged in the modern era
different treatments from different eras included oral oestrogens, orchidectomy and LHRH
agonist therapy.
In addition, both studies included men with non-metastatic as well as metastatic disease. As a result
data findings were based on sub-group analyses, and in the MRC trial the study plan was not always
adhered to, with some controls not receiving treatment on progression.
In both RCTs, no clear survival benefit was shown for patients who started castration therapy with
symptoms versus those who started therapy when no symptoms were present. This data set is limited
as the VACURG study may have included a proportion of patients with symptoms and the MRC
study was confounded by some patients in the delayed therapy arm not receiving therapy.
This would suggest there is not a mandate to commence ADT in patients with asymptomatic
metastases. It should be noted that the MRC and VACURG-1 studies are not therapy versus no
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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