Does Timing of Androgen Deprivation Influence Radiation-Induced Toxicity? A Secondary Analysis of Radiation Therapy Oncology Group Protocol 9413
This study was presented as a poster at the American Society for Therapeutic Radiology and Oncology Annual Meeting, Philadelphia, November 2006.
Received 3 August 2007; accepted 13 November 2007. published online 04 March 2008.
Objectives
We conducted a secondary analysis of the Radiation Therapy Oncology Group protocol 9413 to compare whether the timing of antiandrogen therapy (concomitant versus adjuvant) and testosterone levels influences the incidence of rectal and urinary toxicity in whole pelvic radiotherapy.
Methods
We analyzed two of four study arms, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate. The two arms differed solely in the timing of the total of 4 months of total androgen deprivation: arm I (320 patients, given concomitantly) and arm III (319 patients, given as adjuvant therapy). The influence of testosterone levels (measured at baseline and yearly thereafter) and its recovery on late rectal and urinary toxicity were modeled by multivariate logistic regression analysis and Fine and Gray's regression models.
Results
The occurrence of late rectal toxicity (grade 0–1 versus 2–5, P = 0.16) and late urinary toxicity (grade 0–1 versus 2–5, P = 0.52) was not significantly different statistically between the two arms. The time to testosterone recovery was significantly lower in the adjuvant arm (mean difference of 3.2 months, P = 0.0103). Age and radiation field size are statistically significant risk factors for late urinary toxicity (P = 0.01 and P = 0.02). Baseline testosterone levels, before beginning total androgen deprivation, were a statistically significant predictive factor for late urinary toxicity (P = 0.03).
Conclusions
Older patients and patients with low testosterone levels at baseline are risk factors for late urinary and rectal toxicities, possibly through impaired tissue repair.
aDepartment of Radiation Oncology, Montreal University, Montreal, Quebec, Canada
bDepartment of Statistics, Radiation Therapy Oncology Group, Philadelphia, Pennsylvania
cDepartment of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, California
dDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
eDepartment of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
fDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan
Reprint requests: Daniel Taussky, M.D., Department of Radiation Oncology, Centre Hospitalier Universitaire de Montréal Hôpital Notre-Dame, 1560 Sherbrooke Street East, Montreal, H2L 4M1 QC Canada
This study supported by RTOG U10, CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the National Cancer Institute.
M. Roach is a study investigator funded by GlaxoSmithKline; is a paid consultant to Astra-Zeneca; and is a member of the speaker's bureau for TAP Pharmaceuticals and Siemens.
ABSTRACT