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

3 LOCALLY ADVANCED DISEASE
(Locally advanced/high-risk prostate cancer—de novo
presentation (clinical stage T3–4, and/or early-stage disease
with PSA>20)
3.1 Introduction
In these guidelines locally advanced/high risk prostate cancer is usually defined by clinical stage T3-4
and or early stage disease with PSA>20. However, to establish with certainty that it is locally
advanced can be difficult and apart from clinical staging and the level of PSA, MRI scans can
sometimes be of assistance as well as CT pelvis but both have low sensitivity. The presence of
positive margins in the surgically resected specimen also points to the potential for locally advanced
disease as does an early rise in the PSA, the rate of rise prior to localised treatment has also been
suggested as a potential indicator of metastatic disease. However, in most cases it is the persistent rise
in the PSA that has become a surrogate marker for advanced or metastatic disease after surgical
resection of the prostate. Post radiotherapy if the PSA reaches its nadir and then starts to rise this is
usually used as a surrogate marker of advanced disease. A measurable PSA after radical
prostatectomy does not always indicate residual disease, as it could be due rarely to residual benign
tissue. Biopsy of the prostatic bed can be performed to try to obtain tissue and /or monitoring of the
rate of rise of the PSA in conjunction with knowledge of the Gleason score and presence of positive
or negative margins may provide a means of determining whether the rise is due to a small remnant of
benign tissue rather than metastatic disease.
Androgen Deprivation can be achieved in a number of ways. Testicular androgen production can be
prevented by surgical castration, by chemical castration through the use of LHRH agonists, or by
suppression of androgen production by oestrogens although because of undesirable cardiac side
effects oral oestrogens are now rarely used. The other strategy is to use steroidal and non steroidal
anti-androgens that compete with both testicular and andrenal androgens for the androgen receptor
binding sites. These agents can be used singly and or in combination. It is important to note that there
are some restrictions regarding the prescribing of these agents. LHRH agonists are available on the
RPBS and anti androgens are only available on the PBS (authority) in combination with ADT. The
non steroidal anti-androgens, bicalutamide and flutamide are approved only for use for stage D
(metastatic) disease in combination with LHRH agonist therapy whereas the non-steroidal antiandrogen
, nilutamide, is approved for use in combination with LHRH agonists or orchidectomy for
the treatment of stage C (locally advanced) or D (metastatic prostate cancer). In contrast, the steroidal
anti-androgen ,cyproterone acetate is approved for the treatment of “advanced” prostate cancer.
3.1.1 Androgen deprivation therapy (ADT)
Early versus delayed androgen deprivation therapy
Some patients may not be suitable for definitive local therapy because of co-morbidities or advanced
age. Data are emerging to provide guidance on the timing of ADT for patients with locally advanced
disease and for those with locally advanced disease who decline surgery or radiotherapy. The question
for these patients with no evidence of metastases on imaging is whether to start ADT immediately or
wait until clinical progression (localised or metastatic).
There is an extensive amount of data addressing this issue, covering the period from the 1970s to
2006. This complicates the analysis because of:
issues of stage migration and stage detection with pre bone scan and pre PSA era incorporated
with studies involving patients who are more accurately staged in modern era
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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