RCT: Five-Fraction SBRT Noninferior to Conventional Radiotherapy in Localized Prostate Cancer
20 Oct, 2024 | 15:46h | UTCBackground: Prostate cancer poses a significant global health challenge, with radiotherapy being a common curative treatment for localized disease. Hypofractionation, delivering higher doses per session over fewer treatments, has potential benefits in efficacy and convenience. While moderately hypofractionated radiotherapy is established, the efficacy of stereotactic body radiotherapy (SBRT) delivering radiation in just five fractions remains uncertain.
Objective: To assess whether five-fraction SBRT is noninferior to conventionally or moderately hypofractionated radiotherapy regarding freedom from biochemical or clinical failure in patients with low-to-intermediate-risk localized prostate cancer.
Methods: In this phase 3, international, open-label randomized controlled trial (PACE-B), 874 men with stage T1–T2 prostate cancer, Gleason score ≤3+4, and prostate-specific antigen (PSA) ≤20 ng/mL were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions over 1–2 weeks) or control radiotherapy (78 Gy in 39 fractions over 7.5 weeks or 62 Gy in 20 fractions over 4 weeks). Androgen-deprivation therapy was not permitted. The primary endpoint was freedom from biochemical or clinical failure.
Results: Between August 2012 and January 2018, 874 patients were randomized (433 to SBRT and 441 to control radiotherapy) at 38 centers. Median age was 69.8 years, median PSA was 8.0 ng/mL, and 91.6% had intermediate-risk disease. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% in the SBRT group and 94.6% in the control group (unadjusted HR 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority). Cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects at 5 years was higher with SBRT (26.9% vs. 18.3%; P<0.001), while gastrointestinal toxic effects were similar between groups (10.7% vs. 10.2%; P=0.94). Overall survival did not differ significantly (HR for death, 1.41; 95% CI, 0.90 to 2.20).
Conclusions: Five-fraction SBRT was noninferior to conventional or moderately hypofractionated radiotherapy in terms of biochemical or clinical failure in patients with low-to-intermediate-risk localized prostate cancer. SBRT may be an effective treatment option but is associated with a higher incidence of medium-term genitourinary toxic effects.
Implications for Practice: SBRT offers equivalent oncologic efficacy with the convenience of fewer treatment sessions, potentially reducing patient burden and healthcare resource utilization. Clinicians should consider SBRT for eligible patients but must inform them about the increased medium-term risk of genitourinary toxic effects.
Study Strengths and Limitations: Strengths include a large sample size, multicenter design, standardized radiotherapy protocols, and exclusion of hormonal therapy, minimizing confounding factors. Limitations involve the applicability of findings only to patients similar to those in the trial; some may now opt for active surveillance, and results may not extend to higher-risk populations.
Future Research: Further studies are needed to evaluate long-term outcomes of SBRT, its role in higher-risk patients, and strategies to mitigate genitourinary toxic effects.