Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial.
OBJECTIVE
The late morbidity of a randomized study was analyzed after a follow up of 2 years. The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters. The correlation with acute toxicity and (pre-existing) bowel complaints was investigated.


METHODS
266 T1-4N0M0 prostate cancer patients were randomized for conventional (open fields) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose (66 Gy) and gross target volume-planning target volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self-assessment questionnaire was used to obtain detailed information on morbidity.


RESULTS
At 2 years there is only a trend for less rectal toxicity (grade >/=1) in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10 versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A significant relation was found between late rectal toxicity (grade >/=1) and the volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity. The patient self-assessment questionnaire analysis revealed that patients are most bothered by compliance related symptoms like urgency, soiling and fecal loss. In a multivariate analysis, all other variables loose significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation frequency are accounted for. Late anal toxicity is low and related only to acute anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms. The incidence of grade 2 toxicity increases with a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of treatment.


CONCLUSIONS
Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal, anal and bladder toxicity compared to conventional radiotherapy. There is a significant relationship between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal (and urological) symptoms at start have a major impact on late toxicity.
Koper
Peter C
PC
Erasmus MC/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
Jansen
Peter
P
van Putten
Wim
W
van Os
Marjolein
M
Wijnmaalen
Arend J
AJ
Lebesque
Joos V
JV
Levendag
Peter C
PC
D000368:Aged; D001003:Anal Canal / Q000528:radiation effects*; D000704:Analysis of Variance; D001004:Anus Diseases / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012002:Rectal Diseases / Q000209:etiology; D012007:Rectum / Q000528:radiation effects*; D001743:Urinary Bladder / Q000528:radiation effects*; D001745:Urinary Bladder Diseases / Q000209:etiology