title: Delayed rectal and urinary symptomatology in patients treated for prostate cancer by radiotherapy with or without short term neo-adjuvant androgen deprivation.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Between 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.
  
  
  RESULTS
  Rectal 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.
  
  
  CONCLUSIONS
  Prevalence 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.
authors.affiliation: East Coast Cancer Centre, Tugun, Queensland, Australia. dchristie@wesley.com.au
authors.forename: David
authors.initials: D
authors.lastname: Christie
authors.forename: James
authors.initials: J
authors.lastname: Denham
authors.forename: Allison
authors.initials: A
authors.lastname: Steigler
authors.forename: David
authors.initials: D
authors.lastname: Lamb
authors.forename: Sandra
authors.initials: S
authors.lastname: Turner
authors.forename: Hedy
authors.initials: H
authors.lastname: Mameghan
authors.forename: David
authors.initials: D
authors.lastname: Joseph
authors.forename: John
authors.initials: J
authors.lastname: Matthews
authors.forename: Ian
authors.initials: I
authors.lastname: Franklin
authors.forename: Chris
authors.initials: C
authors.lastname: Atkinson
authors.forename: John
authors.initials: J
authors.lastname: North
authors.forename: Michael
authors.initials: M
authors.lastname: Poulsen
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.forename: Keen-Hun
authors.initials: KH
authors.lastname: Tai
authors.forename: Chris
authors.initials: C
authors.lastname: Wynne
authors.forename: Gillian
authors.initials: G
authors.lastname: Duchesne
authors.forename: Olga
authors.initials: O
authors.lastname: Kovacev
authors.forename: Lynne
authors.initials: L
authors.lastname: Francis
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
authors.forename: Cate
authors.initials: C
authors.lastname: D'Este
authors.forename: Dana
authors.initials: D
authors.lastname: Bill
mesh_terms: D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D001707:Biopsy, Needle; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005242:Fecal Incontinence / Q000453:epidemiology / Q000209:etiology*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D015996:Survival Rate; D013997:Time Factors; D014549:Urinary Incontinence / Q000453:epidemiology / Q000209:etiology*
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen