Impact of neoadjuvant androgen ablation and other factors on late toxicity after external beam prostate radiotherapy

Abstract

Purpose To evaluate the late toxicity profile of prostate cancer patients treated with external beam radiotherapy, to investigate the possible risk factors for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA) is a factor. Methods and materials The study population consisted of 1192 patients with ≥24 months' follow-up. Late GI and GU toxicities were scored with a modified Radiation Therapy Oncology Group/Subjective, Objective, Management, and Analytic scale. All patients were treated with external beam radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either conventional or three-dimensional conformal techniques. Of the 1192 patients, 40% received NAA (median 5 months). Risk factors investigated on multivariate analysis were age, past medical history, use of pelvic fields, dose, fractionation, use and duration of neo- and adjuvant androgen ablation, and acute toxicity (Grade 2 or greater). Results The median follow-up for the group was 49 months (range 24–105). The incidence of late Grade 2-3 GI or GU toxicity was 30% at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk factors of significance in relation to the development of late Grade 3 GU toxicity were coexisting GU disease ( p = 0.02), prior transurethral resection of the prostate or transurethral resection of bladder tumor ( p <0.0001), and presence of acute GU toxicity ( p = 0.012). For late Grade 3 GI toxicity, short-term (≤2 months) NAA ( p = 0.0002) and coexisting GI disease ( p = 0.017) were risk factors. Conclusion Short-term (≤2 months) NAA, but not longer durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The possible mechanism of this phenomenon is unclear.