Conditional Risk and Predictive Factors Associated With Late Toxicity in Patients With Prostate Cancer Treated With External Beam Radiation Therapy Alone in the Randomized Trial RTOG 0126

Abstract

The objective of this study was to characterize the conditional risk of developing a grade 2+ urinary or gastrointestinal toxicity for patients treated with external beam radiotherapy on RTOG 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and later points of follow up. 1,532 patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1,499 were eligible and included in data analysis with a median follow up of 8.4 years (range 0.02-13). Patients were treated with either 3DCRT or IMRT according to institutional practice without the addition of androgen deprivation and randomized to receive either standard dose radiotherapy of 70.2 Gy or dose escalated radiotherapy of 79.2 Gy of radiotherapy to the prostate only with standard fractionation. UVA and MVA analyses were determine if initial factors were predictive of late toxicity at time of treatment and at later timepoints. As patients proceed further from completion of radiotherapy without the development of toxicity, the subsequent risk of both grade 2+ GU and GI toxicity decreased with time. At time of enrollment the risk of developing a grade 2+ toxicity over the next 5 years was 9.57 and 17.89% respectively. After five years of toxicity free survival, the risk of developing a grade 2+ GU or GI toxicity in the subsequent five years was 3.02% and 1.54% respectively. Baseline treatment and patient related factors predicted late toxicity both at trial enrollment and after two years of toxicity free survivorship. Baseline urinary dysfunction and dose escalated radiotherapy were associated with increased late GU toxicity. Acute GI toxicity and dose escalated radiotherapy were associated with increased risk of late GI toxicity. Treatment with IMRT was associated with reduced risk of either toxicity. The conditional risk of grade 2+ toxicities decrease as patients proceed further from treatment with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points.