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

have to be weighed against the impact of ADT on quality of life. This issue is relevant as there is a
large number of men with prostate cancer who are not suitable for definitive local therapy and as these
studies reflect, this is often a disease found in elderly men.
Evidence summary Level References
For locally advanced disease the body of data for androgen
suppressive therapy (medical or surgical) appears consistent in that
immediate treatment shows a disease-specific survival advantage
and on occasion an overall survival advantage. However, the
overall impression suggests that if there is a benefit, it is modest.
Recommendation
II 1-3, 6, 7
No strong recommendation can be made for the use of androgen deprivation therapy in
locally advanced disease. However, there may be a modest benefit for immediate or
primary androgen deprivation therapy for patients with locally advanced disease deemed
not suitable for definitive local therapy. However, this has to be weighed against the impact
of androgen deprivation therapy on quality of life.
Grade C
Choice of androgen deprivation therapy
Given the finding that there is possibly a modest benefit for use of primary ADT for locally advanced
prostate cancer, it is reasonable to ask whether one therapy is better than another. Again, whilst there
is extensive data dating back to the 1970s and the analysis is complicated by the reasons listed in the
dot points above. If primary ADT is to be used, data would support castration. There was one RCT
and two quasi-randomised trials showing a trend towards higher mortality rates with oestrogens as
compared with orchidectomy at four years and longer follow-up, 1, 8-10 and RCTs suggesting a trend
towards lower overall survival with anti-androgens alone when compared with medical or surgical
castration 11 or combined androgen blockade. 12
This leads to the question as to whether combined androgen blockade (CAB) is better than castration
alone for locally advanced disease. There is no definitive comparative trial answering this question in
this patient population, with most trials comparing CAB with castration focusing on metastatic
disease. Subgroup analyses for patients without evidence of metastatic disease (M0) did not show a
survival benefit for combined androgen deprivation for the M0 population 13,14, 15 . The Prostate Cancer
Trialists’ Collaborative Group 13 found a small benefit for non-steroidal anti-androgen plus castration
in M0 and M1 patients combined (12% M0) but did not analyse separately the effects of adding nonsteroidal
anti-androgens for men with non-metastatic disease. Notably, the steroidal anti-androgen,
cyproterone plus castration group was slightly worse than castration alone for the combined group of
M0 and M1. Therefore, there are no data for or against using CAB for locally advanced disease and
the data that do exist suggest no survival benefit. Given the incremental toxicity with CAB, this
additional therapy cannot be used without the risk of a detrimental effect on quality of life. Therefore
there are no data to mandate CAB if primary ADT therapy is going to be used in patients with locally
advanced prostate cancer.
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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