Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial

Abstract

Purpose: To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. Material and methods: FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. Results: Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. Conclusions: In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.