Patterns of toxicity following high-dose-rate brachytherapy boost for prostate cancer: Mature prospective phase I/II study results

Abstract

Background To examine the long-term morbidity of high dose rate brachytherapy boost (HDRBB) in prostate cancer. Patients and methods A phase I/II HDRBB dose escalation protocol recruited 108 men up to November 1999. Treatment combined 46 Gy external beam radiation to the prostate with four fractions of HDR totalling 16 or 20 Gy. Morbidity data were collected prospectively regarding urological, bowel and erectile dysfunction (ED) symptoms using a validated clinician completed instrument. Actuarial incidence and prevalence of symptoms were estimated; the latter to account for potential recovery. Results The median follow-up was 78 months, with 880 questionnaires completed. The respective actuarial cumulative incidence and point prevalence rates of any grade 2 or higher symptom score at 5 years were 24.9% (95% confidence intervals [CI] 16.8–33.5%) and 7.7% (95% CI 1.8–14.5%) for urinary toxicity; and 11.3% (95% CI 5.6–17.1%) and 3.0% (0–7.6%) for rectal toxicity, meaning that most symptom sub-domains showed substantial recovery with time. Corresponding erectile function toxicity figures for the subgroup of men ( n = 53) with normal erectile function prior to treatment and no androgen deprivation therapy were 77.0% (95% CI 64.9–88.1%) and 45.3% (95% CI 27.2–64.6%). Some late toxicity profiles developed after twelve months, typically with low grade bowel and urinary urgency. These peaked at 12–24 months and stayed relatively stable subsequently. Paradoxically, grade 1 or more nocturia symptoms settle with time, despite the accumulation of grade 2 or more toxicity beyond 24 months. Conclusions HDRBB as a means of dose escalation in prostate cancer is associated with low and relatively stable rates of long-term bowel and urinary morbidity, and compares favourably with external beam results. Actuarial incidence methods overstate the burden of toxicity with substantial recovery noted in most domains.