Delayed rectal and urinary symptomatology in patients treated for prostate cancer by radiotherapy with or without short term neo-adjuvant androgen deprivation.
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.
Christie
David
D
East Coast Cancer Centre, Tugun, Queensland, Australia. dchristie@wesley.com.au
Denham
James
J
Steigler
Allison
A
Lamb
David
D
Turner
Sandra
S
Mameghan
Hedy
H
Joseph
David
D
Matthews
John
J
Franklin
Ian
I
Atkinson
Chris
C
North
John
J
Poulsen
Michael
M
Spry
Nigel A
NA
Tai
Keen-Hun
KH
Wynne
Chris
C
Duchesne
Gillian
G
Kovacev
Olga
O
Francis
Lynne
L
Kramar
Andrew
A
D'Este
Cate
C
Bill
Dana
D
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*
D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen