Can Adding Radium-223 to RT Boost Prostate Cancer Outcomes?

Medscape

15-05-2025

Adding radium-223 dichloride (Ra223) to metastasis-directed stereotactic ablative radiotherapy (SABR) did not improve progression-free survival compared with SABR alone in men with bone-only oligometastatic castration-sensitive prostate cancer, according to a phase 2 trial. However, the authors identified two potential prognostic biomarkers — high-risk DNA mutations and T-cell receptor repertoire diversity — to predict progression-free survival outcomes in patients receiving SABR.
METHODOLOGY:
Metastasis-directed SABR has demonstrated benefit in oligometastatic castration-sensitive prostate cancer, but disease progression often occurs in bone.
To assess whether adding Ra223 to SABR would delay disease progression, researchers conducted the multicenter phase 2 RAVENS trial involving 64 men with recurrent oligometastatic castration-sensitive prostate cancer, at least three bone metastases on conventional imaging, and/or at least five bone metastases on molecular imaging.
Patients were randomly assigned to receive either SABR alone (n = 33) or SABR combined with Ra223 (n = 31). Ra223 was administered intravenously at a dose of 55 kBq/kg every 4 weeks for six cycles.
The primary endpoint was progression-free survival, and the secondary endpoints included androgen deprivation therapy–free survival and metastasis-free survival. The median follow-up duration was 18.7 months.
A total of 27 (87%) patients in the Ra223 arm received all six planned cycles of Ra223, and four patients discontinued Ra223 because of disease progression.
TAKEAWAY:
Median progression-free survival was 11.8 months with SABR and 10.5 months with Ra223 plus SABR (adjusted hazard ratio [aHR], 1.42), but the difference was not statistically significant ( P = .24).
= .24). Similarly, metastasis-free survival and androgen deprivation therapy–free survival between the two groups were not significantly different (aHR, 1.09; P = .84, and aHR, 1.53; P = .30, respectively).
= .84, and aHR, 1.53; = .30, respectively). Among those who underwent prostate biopsy, six patients with high-risk mutations in ATM , BRCA1/2 , RB1 , or TP53 had worse progression-free survival (HR, 5.95; P = .003) and metastasis-free survival (HR, 13.1; P = .0026). Greater T-cell receptor diversity was associated with improved progression-free survival, independent of the treatment (aHR, 0.45; P = .04).
, , , or had worse progression-free survival (HR, 5.95; = .003) and metastasis-free survival (HR, 13.1; = .0026). Greater T-cell receptor diversity was associated with improved progression-free survival, independent of the treatment (aHR, 0.45; = .04). Grade 3 treatment-related adverse events occurred in 11% of patients: 6% in the SABR group and 17% in the Ra223 group; lymphopenia was the most common grade 3 event in both groups (3% in the SABR arm and 13% in the Ra223 arm).
IN PRACTICE:
'RAVENS demonstrates, for the first time, that addition of Ra223 to [metastasis-directed] SABR in a castration-sensitive, low-volume bone metastatic state does not delay progression of disease,' the authors wrote. The study also provides evidence for high-risk mutational signature and T-cell receptor repertoire diversity as prognostic biomarkers in oligometastatic castration-sensitive prostate cancer treated with metastasis-directed SABR, they added.
SOURCE:
The study, led by Jarey H. Wang, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, was published online in the Journal of Clinical Oncology .
LIMITATIONS:
The study was open-label and conducted during the COVID-19 pandemic, which may have introduced assessment biases associated with telemedicine encounters. Additionally, the trial was conducted before molecular imaging became routinely used to corroborate disease burden detected on conventional imaging, and molecular imaging was not mandated in the trial.
DISCLOSURES:
The study received funding support through grants from Bayer HealthCare, an anonymous donor, the Movember Foundation – Distinguished Gentleman's Ride, Prostate Cancer Foundation, the National Institutes of Health/National Cancer Institute, and the Department of Defense. Several authors reported receiving research funding or having other ties with various sources.