In Prostate Cancer, 5-Day SBRT Is as Effective as Conventional 5-Week Radiotherapy

Prostate cancer is one of the most common cancers in men, with 1.9 million new diagnoses worldwide each year. Because most patients are diagnosed at an early stage, the effectiveness and adverse-effect profiles of treatment options for early-stage prostate cancer are highly important. Effective treatments with few adverse effects play a critical role in maintaining patients' quality of life and preventing disease progression.

For patients with early-stage prostate cancer that has not spread outside the prostate, 4-week hypofractionated radiotherapy has become a standard treatment. By delivering a high dose in fewer sessions, it aims to achieve effective results in less time than conventional fractionated radiotherapy lasting 5-7 weeks. This approach aims to improve adherence by shortening treatment and to minimize adverse effects.

However, delivered in just 5 sessions, Stereotactic Body Radiotherapy (SBRT) stands out as an ultrahypofractionated treatment option. By delivering high-dose treatment in far fewer sessions than conventional or moderately hypofractionated radiotherapy, SBRT substantially reduces treatment duration.

SBRT's effectiveness compared with conventional or moderately hypofractionated radiotherapy regimens in terms of biochemical or clinical failure had not previously been clearly established. However, on October 16, 2024, The New England Journal of Medicine (NEJM) published this new phase 3, multicenter clinical study, which aims to comprehensively evaluate the effectiveness and safety of SBRT in patients with localized prostate cancer.

The PACE-B Study

This was an international, open-label, randomized, controlled phase 3 trial. Men with stage T1 or T2 prostate cancer , a Gleason score of 3+4 or lower, and a prostate-specific antigen (PSA) level below 20 ng/mL were included.

Patients were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions over 1 or 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 in the study.

The primary aim was to assess freedom from biochemical or clinical failure after treatment—that is, whether patients showed signs such as a rise in PSA (prostate-specific antigen) or clinical disease progression. The study aimed to demonstrate that SBRT did not produce worse outcomes than conventional or moderately hypofractionated radiotherapy (non-inferiority). A hazard ratio of 1.45 was set as the critical threshold. This means that the risk of failure in the SBRT group should not increase by more than 45% compared with the conventional radiotherapy group.

Analyses were performed in the intention-to-treat population. This method evaluates all participants according to the group to which they were randomized, regardless of the treatment they actually received. The approach aims to reflect treatment effectiveness under real-world conditions more accurately.

Results

Between August 2012 and January 2018, a total of 874 patients were randomized at 38 centers: 433 to the SBRT group and 441 to the control radiotherapy group.

The median age was 69.8, and the median PSA level was 8.0 ng/mL. Patients were categorized as low risk in 8.4% of cases and intermediate risk in 91.6% (National Comprehensive Cancer Network, NCCN).

The median follow-up was 74 months, and the 5-year rate of freedom from biochemical or clinical failure was 95.8% (confidence interval [CI], 93.3–97.4%) in the SBRT group, compared with 94.6% (CI, 91.9–96.4%) in the control group.

The unadjusted hazard ratio for biochemical or clinical failure was 0.73 (90% CI, 0.48–1.12; P=0.004), demonstrating the non-inferiority of SBRT.

The rates of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary adverse effects differed significantly between the SBRT and control radiotherapy groups. The 5-year cumulative rate of late genitourinary (urinary tract) adverse effects was 26.9% (CI, 22.8–31.5%) in the SBRT group, compared with 18.3% (CI, 14.8–22.5%) in the control group (P<0.001). There was no significant difference in gastrointestinal adverse effects between the groups (SBRT group 10.7%, CI 8.1–14.2%; control group 10.2%, CI 7.7–13.5%; P=0.94).

Commentary

The results of this phase 3 clinical trial showed that SBRT delivered in 5 fractions was as effective as control radiotherapy in terms of biochemical or clinical failure. SBRT may therefore be an effective treatment option for patients with low- and intermediate-risk localized prostate cancer. However, SBRT had a higher genitourinary toxicity profile, which should be considered in treatment decisions. The study also highlights the importance of long-term follow-up data to better understand SBRT's advantages and disadvantages.