Does timing of androgen deprivation influence radiation-induced toxicity? A secondary analysis of Radiation Therapy Oncology Group protocol 9413

Abstract

4655 Background: We conducted a secondary analysis of RTOG 9413 to compare if the timing of antiandrogen-therapy, concomitant versus adjuvant, influences the incidence of rectal toxicity in whole pelvic radiotherapy. Methods: For the purpose of this secondary analysis, we analyzed the 2 of the 4 arms of the study, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate and excluded the two arms that received prostate only radiotherapy. The 2 arms differed only in the timing of the total of 4 months of total androgen deprivation (TAD): arm I (320 patients), TAD was begun 2 months before the start of radiotherapy and continued during radiotherapy. Arm III (319 patients), TAD started immediately after the completion of radiotherapy. Both acute rectal and acute urinary toxicities (CTC v.2.0), testosterone (measured at baseline and yearly after) and other patients data were modeled using the multivariate logistic regression and the multivariate Cox-proportional hazards regression. Results: Median follow up for all patients is 6.0 and 5.8 years (arm I and II, resp.). 43 (13%) patients in each arm had abnormally low testosterone before start of TAD. Late grade 2 - 5 rectal toxicity occurred in 16% and 13% and urinary toxicity in 18% and 20% (arm I and II, resp.). Frequency (or occurrence) of late rectal toxicity (grade 0–1 vs. 2–5, p = 0.2170) and late urinary toxicity (grade 0–1 vs. 2–5, p = 0.4204) are not significantly different between the two arms. The only risk factors for late rectal toxicity in a multivariate regression model was acute rectal toxicity (OR 1.48, p = 0.025), but not abnormal testosterone level at baseline (p = 0.718) or treatment arm (p = 0.874). For late urinary toxicity: age (OR = 1.588, p = 0.010), RT field size (OR 1.004, p < 0.025), baseline testosterone (OR 1.718, p = 0.028), and acute (grade 2–4) toxicity (OR = 1.664, p = 0.006) but not treatment arm (p = 0.928) were risk factors. Conclusions: While late toxicity was not different for concomitant vs. adjuvant hormonal therapy, an abnormally low testosterone level at baseline is a risk factor for late urinary toxicity and not late rectal toxicity. No significant financial relationships to disclose.