Stereotactic body radiotherapy (SBRT) demonstrated similar safety as standard radiotherapy in patients with low- or intermediate-risk prostate cancer, according to findings from the phase 3 PACE-B trial presented during the 2021 European Society for Radiotherapy and Oncology (ESTRO) Congress.1,2
The results showed that using SBRT to reduce the number of treatment sessions with fewer, more intense treatments did not lead to an increase in gastrointestinal or genitourinary acute toxicity.Compared with the standard radiotherapy arm, the rate of grade ≥2 severe gastrointestinal adverse events (AEs) was about 2 percentage points lower in the SBRT arm (P =.38, showing noninferiority). Regarding grade ≥2 severe genitourinary AEs, the incidence rate was about 4 percentage points lower in the SBRT arm (P = .16, showing noninferiority).
“At The Royal Marsden and The Institute of Cancer Research (ICR), we are focused on developing smarter, better and kinder treatments for patients across the UK and internationally. Developments in radiotherapy, such as SBRT, mean we can target tumors much more effectively,” chief study investigator Nicholas van As, MBBCH MRCP FRCR MD(res), Medical Director and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, and reader in Precision Prostate Radiotherapy, ICR, London, stated in a news release. “It is reassuring to see from this trial that SBRT does not significantly impact patients’ quality of life, compared with the current standard of care. Using SBRT to deliver this treatment would mean that patients could be spared numerous visits to hospital, allowing them to get back to their lives sooner.”
SBRT enables the delivery of radiotherapy with sub-millimeter precision and can be delivered to patients by clinicians with a CyberKnife or standard radiotherapy machine.
The international, open-label, noninferiority PACE-B trial enrolled patients aged ≥18 years with low- or intermediate-risk prostate adenocarcinoma (excluding Gleason 4 + 3) scheduled to receive radiotherapy. Patients had a WHO performance status of 0 to 2. Androgen-deprivation therapy was not allowed.
Enrollment occurred between August 7, 2012, and January 4, 2018, at 37 centers in the UK, Ireland, and Canada. A total of 874 men were randomized to SBRT (n = 433) or standard radiotherapy (n = 441). Patients in the conventionally fractionated control arm received either 39 doses (78 Gy in 39 fractions over 7.8 weeks) or 20 doses (62 Gy in 20 fractions over 4 weeks), and men in the SBRT arm received only 5 doses (36.25 Gy in 5 fractions over 1-2 weeks).
“Our aim was to understand whether we could safely increase the dose of targeted radiation per day, allowing us to reduce number of treatments required. We wanted to measure whether this could be done without changing the low level of side effects we see with modern prostate radiotherapy. When treating patients, we have to consider whether the higher doses in a shorter time period is the best option; the potential side effects are a critical factor in making this decision,” Alison Tree, MBBS BSc FRCR MD(Res), consultant clinical oncologist at The Royal Marsden NHS Foundation Trust, and leader of the Uro-oncology Clinical Trials team at ICR, who presented the data at ESTRO, stated in the release.
Overall, 98% (n = 432) of the conventionally fractionated or moderately hypofractionated radiotherapy control arm and 96% (n = 415) of the SBRT arm received ≥1 fraction of the treatment to which they were randomized. Of these patients, grade ≥2 severe gastrointestinal AEs occurred in 12% of the control arm versus 10% of the SBRT arm (difference, −1.9 percentage points) and grade ≥2 severe genitourinary AEs occurred in 27% versus 23% of the 2 arms, respectively (difference, −4.2 percentage points). There were no deaths related to study treatment in either arm.
Although bowel and rectal AEs were comparable between the study arms, urinary toxicity was slightly higher with SBRT. Specifically, the investigators determined that 1 of 9 patients who receive SBRT will develop moderate bladder AEs (eg, urinary frequency and urgency) 2 years’ posttherapy compared with 1 in 17 patients treated with standard radiotherapy. However, the researchers still concluded that, overall, safety was comparable between the radiotherapy approaches.
“Now we know that longer-term side effects of SBRT are similar to those with standard radiotherapy. If we can also show that cancer control is no worse, then we expect our trial to be practice-changing,” Emma Hall, PhD, deputy director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, stated in the release.
1. Shorter course of radiotherapy safely delivers treatment for prostate cancer. Published online August 31, 2021. Accessed September 2, 2021. https://bit.ly/3zErctX
2. Brand DH, Tree AC, Ostler P, et al. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2019;20(11):1531-1543. doi: 10.1016/S1470-2045(19)30569-8