• David Christie, James Denham, Allison Steigler, David Lamb, Sandra Turner, Hedy Mameghan, David Joseph, John Matthews, Ian Franklin, Chris Atkinson, John North, Michael Poulsen, Nigel A Spry, Keen-Hun Tai, Chris Wynne, Gillian Duchesne, Olga Kovacev, Lynne Francis, Andrew Kramar, Cate D'Este, and Dana Bill.
• East Coast Cancer Centre, Tugun, Queensland, Australia. dchristie@wesley.com.au
• Radiother Oncol. 2005 Nov 1; 77 (2): 117-25.

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.

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