As reported in The Lancet Oncology by Tree et al, an analysis from the phase III PACE-B trial has shown no difference in 2-year genitourinary or gastrointestinal toxicity with conventionally fractionated/moderately hypofractionated intensity-modulated radiotherapy (IMRT) vs highly hypofractionated stereotactic body radiotherapy (SBRT) in men with low- or intermediate-risk localized prostate adenocarcinoma.
The primary endpoint of the noninferiority trial is 5-year freedom from biochemical or clinical failure—data on which are not yet mature. A prior report showed no difference between radiotherapy regimens in terms of short-term toxicity.
Study Details
The open-label trial included 874 patients from sites in the United Kingdom, Ireland, and Canada. They were randomly assigned between August 2012 and January 2018 to receive radiotherapy consisting of 78 Gy in 39 fractions over 7.8 weeks or, following protocol amendment in March 2016, 62 Gy in 20 fractions over 4 weeks (control RT group, n = 441) or SBRT at 36.25 Gy in 5 fractions over 1 to 2 weeks (n = 433). Androgen deprivation was not permitted. The primary outcome measures for the current toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade ≥ 2 genitourinary and gastrointestinal toxicities at 24 months after radiotherapy. A total of 381 (genitourinary toxicity) or 382 patients (gastrointestinal toxicity) in the control RT group and 384 patients (both genitourinary and gastrointestinal toxicity) had 24-month toxicity assessments and were included in the current analysis.
Key Findings
At 24 months, RTOG grade ≥ 2 genitourinary toxicity was observed in 8 (2%) of 381 patients in the control RT group vs 13 (3%) of 384 patients in the SBRT group (absolute difference = 1.3%, 95% confidence interval [CI] = –1.3% to 4.0%, P = .39). Grade 2 and grade 3 toxicity were observed in 7 (2%) vs 11 patients (3%) and in 1 (< 1%) vs 2 patients (< 1%), respectively. No grade ≥ 4 toxicity was observed. Grade 1 toxicity was observed in 53 (14%) vs 72 patients (19%).
At 24 months, RTOG grade ≥ 2 gastrointestinal toxicity was observed in 11 (3%) of 382 patients in the control RT group vs 6 (2%) of 384 patients in the SBRT group (absolute difference = –1.3%, 95% CI = –3.9% to 1.1%, P = .32). Grade 2 and grade 3 toxicity were observed in eight (2%) vs six patients (2%) and in three (1%) vs 0 patients, respectively. No grade ≥ 4 toxicity was observed. Grade 1 toxicity was observed in 51 patients (13%) vs 55 patients (14%).
No treatment-related deaths were reported.
The investigators concluded: “In the PACE-B trial, 2-year RTOG toxicity rates were similar for five-fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side effects. Biochemical outcomes are awaited.”
Alison Tree, MDRes, of The Royal Marsden Hospital, London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Accuray. For full disclosures of the study authors, visit thelancet.com.
