Stereotactic body radiotherapy (SBRT) has demonstrated non-inferiority compared to standard radiotherapy in the treatment of localized prostate cancer, according to the results of the international randomized phase 3 PACE-B trial (NCT01584258). The study, published in the New England Journal of Medicine, indicates that a five-fraction SBRT regimen is a feasible option for patients with low- to intermediate-risk disease, offering similar biochemical or clinical failure rates as conventional radiotherapy.
The trial, conducted across the United Kingdom, Ireland, and Canada, involved 874 male patients with stage T1 or T2 prostate cancer. Participants were randomized into two groups: one receiving SBRT (36.25 Gy in five fractions) and the other undergoing control radiotherapy (initially 78 Gy in 39 fractions, later amended to 62 Gy in 20 fractions). The primary endpoint was freedom from biochemical or clinical failure.
At a median follow-up of 74.0 months, the 5-year incidence of 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. This translated to an unadjusted hazard ratio for biochemical or clinical failure of 0.73 (90% CI, 0.48-1.12; P = .004 for non-inferiority). According to the researchers, the estimated absolute difference in the percentage of patients event-free at 5 years was 1.4 percentage points (90% CI, -0.6 to 2.8).
Clinical Implications of SBRT
"The high 5-year incidence of biochemical control and the acceptable [adverse effect] profile, coupled with the considerable advancements in radiotherapy delivery, underscore the potential of the use of SBRT in prostate cancer treatment," wrote lead study author N. van As, MD, of the Royal Marsden Health, in the United Kingdom, and coinvestigators. The reduced number of treatment fractions associated with SBRT could alleviate the burden on healthcare systems while maintaining favorable cancer-control outcomes without the need for hormonal treatment.
Safety and Adverse Effects
Regarding safety, Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary adverse effects (AEs) at 5 years occurred in 7.3% of patients in the SBRT group and 4.5% of those in the control radiotherapy group (P = .11). Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher genitourinary AEs occurred in 8.7% in the SBRT group and 6.7% in the control radiotherapy group (P = .32). RTOG grade 2 or higher gastrointestinal AEs were rare, occurring in 0.8% and 0.3% of patients in the SBRT and control radiotherapy groups, respectively.
CTCAE grade 2 or higher erectile dysfunction was present in 26.4% of SBRT-treated patients vs 29.1% of those treated with control radiotherapy (P = .46). Treatment-related serious AEs occurred in 6 patients in each arm. There were 79 deaths in total (46 in the SBRT group and 33 in the control radiotherapy group); 4 deaths were due to prostate cancer (n = 2 in each arm) and 28 were a result of other primary cancers (HR, 1.41; 95% CI, 0.90-2.20).
Additional Considerations
The authors noted that when the trial was designed, there were no NCCN classifications for the favorability of intermediate-risk disease, though now most patients would be classified as having unfavorable intermediate-risk cancer. This highlights the evolving understanding of risk stratification in prostate cancer and the potential for further refinement of treatment strategies.
Expert Commentary
Dr. Seth Blacksburg, chief medical officer of Accuray, stated that the results of the PACE-B trial are a "game-changer" and provide compelling data supporting the use of prostate SBRT for early-stage disease. He emphasized that SBRT offers highly effective cancer therapy while significantly reducing the disruption to patients' lives compared to traditional schedules.
