Men undergoing treatment for prostate cancer could be safely given far less radiotherapy, a major trial has found, the results also showing that after five years, 96% of the men who received five doses of the multi-beam radiotherapy were cancer-free, compared with 95% who received at least 20 doses of standard radiotherapy.
The scientists involved in the trial said that doses could be slashed by three-quarters meaning five higher doses will be enough, instead of the 20 or so given now. Additionally, side effects, such as needing to pass urine more often, were low in both groups.
The international trial involved nearly 900 men with medium-risk prostate cancer that had not spread.
Lead researcher Prof Nicholas van As from the Royal Marsden Hospital in Britain said the results were “outstanding” and “fantastic” for patients.
Prostate Cancer UK said the finding had the potential to save time and money for the NHS, while still giving men the best outcomes.
It means thousands of men could be given larger doses of radiotherapy – also known as multi-beam radiotherapy – at each hospital visit, but less overall.
The top-line results of the PACE-B trial were released at the American Society for Therapeutic Radiation and Oncology (Astro) conference in San Diego recently.
Van As said he expected the results to lead to “enormous change” in the way radiotherapy was delivered, and that the NHS would probably “rapidly adopt” the lower-dose treatment.
“Across the whole NHS, which is under pressure, that’s hundreds of thousands of doses of radiotherapy that are going to be saved,” he pointed out.
In the UK, 20 doses of radiotherapy are the standard treatment, but in other countries like the US, they use up to 40 doses.
Another key element of the trial was that none of the 874 men was given any hormone therapy to block testosterone, a driver of prostate cancer.
Hormone therapy has multiple side effects including severe tiredness, hot flushes and low libido.
Study details
5-Year Outcomes from PACE B: An International Phase III Randomised Controlled Trial Comparing Stereotactic Body Radiotherapy (SBRT) vs. Conventionally Fractionated or Moderately Hypo Fractionated External Beam Radiotherapy for Localized Prostate Cancer
N. van As, J. Patel, P. Ostler, E. Hall, et al.
Presented at ASTRO 2023
Purpose/Objective(s)
External beam radiotherapy (EBRT) is a curative treatment for Localized Prostate Cancer (LPCa). Large randomised controlled trials (RCTs) have shown moderately hypo fractionated regimens (2.5 − 3 Gy/fraction(f)) as non-inferior to 2Gy/f regimens. PACE-B aims to demonstrate non-inferiority of SBRT compared to conventionally or moderately hypo fractionated regimens for biochemical and/or clinical failure (BCF).
Materials/Methods
PACE (NCT01584258) is an international phase III open-label multiple-cohort RCT. Men with LPCa, stage T1-T2, ≤ Gleason 3 + 4, PSA ≤ 20 ng/mL, unsuitable for surgery or preferring EBRT, were eligible. Participants (pts) were randomised (1:1) to SBRT (36.25 Gy / 5f in 1- 2 weeks (wks)) or control radiotherapy (CRT) (78 Gy / 39 f over 7.5 wks, or 62 Gy / 20 f in 4 wks) to the planning target volume. Androgen deprivation therapy was not permitted. The primary endpoint was freedom from biochemical (BF)/clinical (CF) failure. BF is based on PSA rises, commencement of ADT or date of orchiectomy and CF is based on local recurrence, nodal recurrence, distant metastases and death from prostate cancer. 858 pts were needed to rule out 6% inferiority (80% power, one-sided alpha 5%) assuming 85% event-free rate with CRT, corresponding to a critical hazard ratio (HR) of 1.45. Analysis was done by intention to treat. Results: 874 pts were randomised from 38 centres (n=441 (CRT) and n=433 (SBRT)) between 08/2012 and 01/2018. Baseline characteristics were well balanced across CRT and SBRT groups: median age 69.8 years (IQR 65.4,74.0); median PSA ng/mL (IQR): 8.1 (6.3,11) vs 7.9 (5.5,10.9); NCCN risk group 9.3% low, 90.7% intermediate. With median follow-up of 73.1 months (IQR 62.6, 84.0), 5-year BCF event free-rate (95% CI) was 94.6% (91.9% – 96.4%) vs 95.7% (93.2% – 97.3%) for CRT and SBRT groups respectively. SBRT was non inferior to CRT with unadjusted HR (90% CI) = 0.74 (0.47 – 1.17), pvalue for non-inferiority=0.007. The estimated absolute differences in the proportion of patients event free in the SBRT group compared with that in the CRT group at 5 years was: 1.36% (90% CI: 0.87 – 2.80). At 5 years, RTOG grade 2 or worst (G2+) genitourinary toxicity was seen in 3.2% (11/348) pts who received CRT and 5.5% (20/363) pts who received SBRT (p=0.14); RTOG G2+gastrointestinal toxicity was seen in 1/348 receiving CRT and 1/ 363 received SBRT (p=0.99
Conclusion
Five-year BCF free rates are high in PACE-B participants. After median follow-up of six years, five-fraction-SBRT is non-inferior to CRT for BCF. SBRT reduces pts attendances, shortens treatment time and 5 fraction SBRT should be a new standard of care for pts with low/favourable intermediate risk LPCa.
BBC News article – Prostate cancer trial: Radiotherapy doses can be cut safely (Open access)
See more from MedicalBrief archives:
MRI scans ‘revolutionise’ prostate cancer diagnosis – UK study
Monitoring, not treatment, better for low-risk prostate cancer – US study
Prostate cancer patients can delay treatment without increased death risk – long-term study