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

Microscopic fully resected node positive disease
There was a single RCT examining the effects of long-term adjuvant castration therapy for patients
with microscopic fully resected node-positive disease. 18 Unfortunately it was of medium quality as it
was not blinded and it was closed early due to poor accrual. It therefore had small numbers and low
power. There was a hazard ratio for survival of 3.0 with a median follow-up of 7.1 years 18 and 2.14
with longer follow-up (median follow-up of 11.9 years, which was published in June 2006) 101
favouring the long-term ADT arm. The notion of systemic therapy being beneficial is possibly
consistent with the benefit seen in patients with high-risk disease treated with ADT and radiotherapy
versus radiotherapy alone. The clinical impact of this data set is limited to patients with lymph node
positive disease that has been resected. Only patients with pathological node-positive prostate cancer
to undergo a lymph node dissection, which further supports performing the procedure in patients with
high-risk prostate cancer.
It should be highlighted that the toxicity for patients on androgen deprivation is significant, with
unwanted effects in terms of cardiovascular, genitourinary (impotency) systems as well as weight gain
and gynaecomastia causing significant problems for a minority of patients (see Complications and
cumulative treatment toxicity under section 3.1.1). The problem of hot flushes was rated as highly
significant, affecting 59%. 18 It should be noted that since this publication, a greater awareness of other
untoward effects of ADT (such as bone substance loss and its consequences, the metabolic syndrome
and cognitive problems) has occurred.
The translation of these data into practice is limited to patients with fully resected lymph node
positive disease. It must therefore be emphasised that a lymph node dissection be undertaken. The use
of ADT as adjuvant therapy for informed patients with lymph node positive disease in the Australian
medical system is applicable, as the PBS requires patients to have ‘locally advanced (equivalent to
stage C) disease’ (PBS wording).
Evidence summary Level References
Neither of two RCTs for locally advanced disease (pT3–4No/Nx),
neither of which showed a survival benefit for post-operative longterm
anti-androgen therapy.
The effects of castration therapy as an adjuvant to prostatectomy
have not been reported in an RCT.
For fully resected node-positive disease there is evidence of overall
survival advantage in one study that was closed early.
Recommendations
II 6, 23
II 18
For locally advanced prostate cancer, anti-androgens as an adjuvant monotherapy to
radical prostatectomy are not recommended.
Grade B
35
Locally advanced disease