A recent phase III trial, PACE-B, published in The New England Journal of Medicine, has revealed that stereotactic body radiotherapy (SBRT) is non-inferior to conventionally fractionated radiotherapy in managing biochemical or clinical failure in patients with low- to intermediate-risk localized prostate cancer. This finding suggests SBRT could be an effective alternative, offering a shorter treatment duration.
The open-label, non-inferiority trial, conducted across sites in the United Kingdom, Ireland, and Canada, involved 874 patients with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen level ≤ 20 ng/mL. Participants were randomized to receive either SBRT (36.25 Gy in 5 fractions over 1-2 weeks, n = 433) or conventional radiotherapy (78 Gy in 39 fractions over 7.5 weeks or 62 Gy in 20 fractions over 4 weeks, n = 441). Androgen-deprivation therapy was not permitted during the trial.
The primary outcome was freedom from biochemical or clinical failure, with a non-inferiority margin set at a hazard ratio of 1.45.
Efficacy of SBRT
After a median follow-up of 74.0 months, the 5-year freedom from biochemical or clinical failure was 95.8% (95% CI = 93.3%–97.4%) in the SBRT group and 94.6% (95% CI = 91.9%–96.4%) in the control radiotherapy group (HR = 0.73, 90% CI = 0.48–1.12, P = .004 for non-inferiority). Although a post hoc test for superiority was not significant (HR = 0.73, 95% CI = 0.44–1.21, P = 0.22), the results support SBRT as a viable option. The initiation of hormone therapy was less frequent in the SBRT group (10 patients) compared to the control group (19 patients; HR = 0.55, 95% CI = 0.26–1.20).
Toxicity Considerations
While SBRT demonstrated non-inferiority in efficacy, it was associated with a higher incidence of late genitourinary toxicity. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group grade ≥ 2 genitourinary toxic effects was 26.9% (95% CI = 22.8%–31.5%) in the SBRT group compared to 18.3% (95% CI = 14.8%–22.5%) in the control group (P < .001). Gastrointestinal toxic effects were similar between the two groups, with a cumulative incidence of late grade ≥ 2 events of 10.7% (95% CI = 8.1%–14.2%) in the SBRT group and 10.2% (95% CI = 7.7%–13.5%) in the control group (P = .94).
Clinical Implications
The study's lead author, Dr. Nicholas van As from Royal Marsden Hospital, London, stated that five-fraction SBRT could be an efficacious treatment option for patients with low- to intermediate-risk localized prostate cancer, as defined in the trial. These findings offer a potential for reduced treatment duration, which could improve patient convenience and resource utilization, though careful consideration of potential genitourinary toxicity is warranted.
