SBRT Is Feasible for Localized Prostate Cancer

Stereotactic body radiotherapy showed noninferior biochemical or clinical failure compared with standard radiotherapy in prostate cancer.

Five-fraction stereotactic body radiotherapy (SBRT) was not inferior to control radiotherapy when it came to biochemical or clinical failure in patients with low- to intermediate-risk localized prostate cancer, according to findings from an international randomized phase 3 trial called PACE-B (NCT01584258).

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 (unadjusted HR for biochemical or clinical failure, 0.73; 90% CI, 0.48-1.12; P = .004 for noninferiority) at a median follow-up of 74.0 months. The estimated absolute difference in the percentage of patients in the SBRT group compared with the control radiotherapy group who were event-free at 5 years was 1.4 percentage points (90% CI, ˗0.6 to 2.8).

“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,” lead study author N. van As, MD, of the Royal Marsden Health, in the United Kingdom, and coinvestigators wrote in the publication. “The reduction in treatment fractions would alleviate the burden on health care systems while yielding favorable cancer-control outcomes without the addition of hormonal treatment.”

In the trial, 874 male patients (433 in the SBRT group vs 441 in the control radiotherapy group) were randomized across the United Kingdom, Ireland, and Canada. A total 414 patients in the SBRT group and 424 patients in the control radiotherapy group received their assigned treatment. Twenty-five patients did not receive either treatment, and 11 were deemed ineligible.

To be eligible for enrollment, men were required to have stage T1 or T2 prostate cancer, a prostate-specific antigen (PSA) level of 10 or lower ng/mL (low risk) or 10.1 ng/mL to 20 ng/mL (intermediate risk), and a Gleason score of 3+3 (low risk) or 3+4 (intermediate risk). Exclusion criteria included Gleason grade 4 or higher disease, previous pelvic radiotherapy, prior treatment for prostate cancer, prostheses in both hips, and any NCCN high-risk factors.

The trial’s primary endpoint was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45.

The median PSA level was 8.0 ng/mL (IQR, 5.9-11.0) and the median age was 69.8 years (IQR, 65.4-74.0). The NCCN risk category was low-risk disease in 8.4% of patients vs 91.6% of those with with intermediate-risk disease.

Treatment for SBRT was a total dose of 36.25 Gy in five fractions given over a period of 1 or 2 weeks that 95% of the planning target volume received. A secondary target dose of 40 Gy was administered to 95% of the clinical target volume only. Insertion of at least 3 prostatic fiducial markers was recommended. Protocol for control radiotherapy mandated 78 Gy in 39 fractions over 7.5 weeks initially, but after an amendment, 62 Gy in 20 fractions over 4 weeks was permitted.

For 74.9% of patients, SBRT was delivered over 2 weeks and in 40.7% of patients with the CyberKnife device (Accuray). Fiducial marker use was more common with SBRT (73.0%) vs control radiotherapy (56.6%).

Hormone therapy occurred in 29 patients (10 in the SBRT group vs 19 in the control radiotherapy group; HR, 0.55; 95% CI, 0.26-1.20).

Regarding safety at 5 years, 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 in 4.5% of those in the control radiotherapy group (P = .11). Common Terminology Criteria for Adverse Events grade 2 or higher genitourinary AEs occurred in 8.7% in the SBRT group and in 6.7% in the control radiotherapy group (P = .32). RTOG grade 2 or higher gastrointestinal AEs occurred in 0.8% and 0.3% of patients in the SBRT and control radiotherapy group, 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).

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.

Reference

van As N, Griffin C, Tree A, et al. Phase 3 trial of stereotactic body radiotherapy in localized prostate cancer. N Engl J Med. 2024;391(15):1413-1425. doi:10.1056/NEJMoa2403365