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

trials ADT consisted of an LHRH agonist and a non-steroidal anti-androgen, flutamide. All trials were
consistent, with no increase in acute or late urinary or bowel toxicity reported with the addition of
androgen blockade.
A fourth trial, RTOG 83-07, compared Megestrol versus Diethylstilbestrol. 96 These drugs would not
be routinely used as first-line therapy and as such this trial was not considered further.
The effect of short-term versus long-term androgen deprivation on radiotherapy toxicities
One RCT, RTOG 92-02, 97, 98 compared short-term with long-term androgen deprivation (four months
neoadjuvant plus concurrent LHRH agonist and non-steroidal anti-androgen, flutamide, with or
without two years of adjuvant LHRH agonist). This trial used whole pelvis radiotherapy. A
statistically significant increase in late RTOG gastrointestinal toxicity grade 3–5 was reported with
long-term ADT although absolute rates were low (3 versus 1%, p=0.04) and grade 4 or 5 toxicities
were less than 1%. 97
Accounting for differences in reporting of toxicity the evidence suggests that there is no significant
increase in radiotherapy toxicity with the addition of ADT. It should be noted that sexual function is
inadequately assessed in these studies. Only one trial has reported an increase in late impotence with
six months of androgen deprivation. 30
Evidence summary Level References
There does not appear to be any difference in radiotherapy
toxicities (urinary and gastrointestinal) with the addition of androgen
deprivation therapy to radiotherapy, although it is acknowledged
that sexual function has been inadequately assessed in these
studies.
Recommendation
II 26, 27, 29,
30, 92,93,94,
97, 98
Androgen deprivation therapy can be used in combination with radiotherapy without
additional radiotherapy toxicities (urinary and gastrointestinal). Effect on sexual functioning
has not been defined.
Grade C
3.1.4 Surgery
Surgery for men with locally advanced disease has been rarely reported in the literature. Where it has
been performed it has frequently been accompanied by ADT and it has been difficult to separate the
effect of the ADT from surgery. It has been possible to identify three randomised studies published
prior to 2006 of surgical interventions for the treatment of prostate cancer that included patients with
locally advanced disease.
In 1994 Isaka et al 86 reported a randomised trial comparing radical prostatectomy and external beam
radiotherapy for men with stage B2 and C disease. Both arms had neoadjuvant and adjuvant endocrine
therapy. The follow-up of 100 patients entered was very short, an average of 25 months. There was
only one cancer death and no conclusions could be drawn.
Akakura et al 1999 84 published an update of the 1994 study. The follow-up was still relatively short at
a median of 58.5 months and given the trial design, it was not possible to isolate the effect of ADT on
patient survival. However, the progression-free and cause-specific survival at five years was superior
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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