5153 Background: iPSA and BF are often poor predictors of mortality in men treated for locally advanced PC. We sought to find out why from prospective randomised trial data. Methods: In the TROG 96.01 trial men with T2b,c, 3, 4 N0 PC were randomised to 0, 3 or 6 months maximal androgen deprivation (AD) (goserelin 3.6 mg sc monthly and flutamide 250 mg po tid) prior to 66 Gy to the prostate and seminal vesicles. Failure site was diagnosed prior to salvage hormone therapy (ST) where possible, and type, timing and duration of response to ST recorded. Proportional hazards modeling was used to identify predictors of cause specific and overall survival (CSS, OS) at follow-up landmark points (where p>0.05=NS, <0.01=S, <0.001=H). Results: Between 1996 and 2000, 802 eligible men were randomised. Higher iPSA was found to be a potent predictor of BF (Houston [HF])H but a poor one for of CSSNS and OSNS. Patients having HF and/or clinical failure had unfavourable initial prognostic factors (high iPSAH, stageH, Gleason scoreH or risk groupH) compared to patients who did not fail. However in this cohort poor initial prognostic features did not predict PC death when the relapse characteristics (failure siteH and PSA doubling timeH [PSA DT]) were accounted for. Instead lower iPSA levels were predictive of worse outcome in these modelsS, a finding supported by univariate analyses. PSA DT was found to correlate positively with interval between HF and STH and the likelihoodS and duration of response to STH, and survivalH. Thus lower PSA DTs were associated with earlier intervention but poorer responses and outcomes. Conclusions: Prognosis after BF is related more to tumour biology at relapse than to initial prognostic factors. ST alone is an unsatisfactory treatment for rapid PSA DT relapses. No significant financial relationships to disclose.

Background and purposeTo identify contributing factors to delayed rectal and urinary symptoms in a randomised trial comparing different durations of maximal androgen deprivation (MAD), given prior to radiotherapy, for locally advanced prostate cancer.Patients and methodsBetween 1996 and 2000, 818 patients with stages T2b,c, 3 and 4 prostate cancer were entered into a trial comparing 0, 3 and 6 months of MAD prior to and during radiotherapy. Their delayed normal tissue effects were recorded by their treating doctors using standardised scales and by the patients using a self-assessment questionnaire regularly. Time to occurrence and prevalence data were analysed.ResultsRectal and urinary symptom levels were observed to vary markedly over time in at least 80% of patients, with some indicating lasting resolution of symptoms. Prevalence rates were found to be substantially lower than actuarial probability rates. Baseline symptom levels and greatest acute symptom levels were both very powerful predictors.Obstructive lower urinary tract symptoms were noted to improve during the first 4 years after radiotherapy in approximately 60% of cases in each treatment arm. However, the treatment arm itself was not shown to influence these improvements in other univariate or multivariate analyses. MAD was shown to reduce both time to occurrence and prevalence of delayed proctopathic symptoms, but this effect was confirmed statistically in the 3 month treatment arm only. Multivariate models indicated that higher levels of haemoglobin prior to any treatment may in some way protect against delayed proctopathic symptoms.ConclusionsPrevalence data provide more clinically meaningful estimates of risk of delayed effects in normal tissues where assessment relies substantially on reported symptom levels. In these tissues consideration of the impact of baseline symptom levels and pathologies, and greatest acute symptom levels in analyses of delayed effects appears mandatory.Obstructive lower urinary symptoms improve over several years in the majority of patients treated for locally advanced prostate cancer by radiotherapy. Future research could address whether rectal toxicity is affected by initial haemoglobin levels and declines in it due to MAD.