**TOPLINE: Key Findings on Radium-223 and SABR**
In a groundbreaking phase 2 trial, the combination of **radium-223 dichloride (Ra223)** with **metastasis-directed stereotactic ablative radiotherapy (SABR)** has not proven to enhance progression-free survival when compared to SABR alone in men facing **bone-only oligometastatic castration-sensitive prostate cancer**. Nevertheless, researchers have spotlighted two promising prognostic biomarkers—**high-risk DNA mutations** and **T-cell receptor repertoire diversity**—that may potentially predict patient outcomes.
**METHODOLOGY: How the Trial Unfolded**
- Metastasis-directed SABR has shown significant promise in treating oligometastatic castration-sensitive prostate cancer, yet disease progression commonly manifests in the bones.
- To evaluate whether adding Ra223 could prolong this progression, the **multicenter phase 2 RAVENS trial** engaged 64 men diagnosed with recurrent oligometastatic castration-sensitive prostate cancer, presenting with a minimum of three bone metastases on standard imaging or five on molecular imaging.
- Participants were randomly divided into two groups: 33 men received **SABR alone**, while 31 men were treated with **both SABR and Ra223**, administered intravenously at **55 kBq/kg every four weeks for six cycles**.
- This study sought to assess primary endpoints, namely **progression-free survival**, alongside secondary measures such as **androgen deprivation therapy–free survival** and **metastasis-free survival**, with a median follow-up period of **18.7 months**.
- An impressive **87%** of the Ra223 group completed all planned six treatment cycles, despite four patients withdrawing due to disease progression.
**TAKEAWAY: What the Results Reveal**
- **Median progression-free survival** showed 11.8 months for the SABR group compared to 10.5 months for those receiving Ra223 in addition to SABR (adjusted hazard ratio **[aHR]**: 1.42), with no statistically significant difference (**P = .24**).
- Likewise, metrics for metastasis-free survival and **androgen deprivation therapy-free survival** indicated no substantial variation between the two arms (aHR: 1.09; **P = .84**, and aHR: 1.53; **P = .30**).
- Crucially, patients undergoing **prostate biopsy** displayed alarming outcomes: six individuals with high-risk mutations in **ATM, BRCA1/2, RB1**, or **TP53** experienced markedly worse progression-free survival (HR: 5.95; **P = .003**) and metastasis-free survival (HR: 13.1; **P = .0026**). A greater diversity in the **T-cell receptor repertoire** significantly correlated with improved progression-free survival, irrespective of the treatment (aHR: 0.45; **P = .04**).
- **Adverse effects** were noted, with **11%** of patients facing grade 3 treatment-related complications—6% in the SABR group and 17% in the Ra223 cohort, primarily due to lymphopenia (3% in SABR; 13% in Ra223).
**IN PRACTICE: Implications for Treatment**
The RAVENS trial marks a significant milestone, illustrating for the first time that supplementation of Ra223 to **metastasis-directed SABR** in a castration-sensitive, low-volume bone metastatic context does not delay disease progression. This research additionally highlights the potential of high-risk mutational signatures and **T-cell receptor repertoire diversity** as **prognostic biomarkers** in the treatment landscape for oligometastatic castration-sensitive prostate cancer.
**SOURCE: Where to Learn More**
This pivotal study, spearheaded by **Jarey H. Wang, MD, PhD**, from **Johns Hopkins University School of Medicine**, has been published online in the esteemed Journal of Clinical Oncology.
**LIMITATIONS: Points for Reflection**
It is important to consider the limitations of the study, including its open-label design and the fact it was conducted during the **COVID-19 pandemic**—factors that may have unintentionally influenced assessment biases linked to telemedicine. Additionally, the use of **molecular imaging**—which could corroborate disease burden identified through conventional imaging—was not mandated, possibly impacting results.
**DISCLOSURES: Funding and Affiliations**
This significant research effort received vital financial backing through grants from **Bayer HealthCare**, anonymous donors, the **Movember Foundation**, the **Prostate Cancer Foundation**, the **National Institutes of Health/National Cancer Institute**, and the **Department of Defense**. Several authors disclosed ties to various funding sources.
This article is the product of multiple editorial tools, including AI, and has been supplemented by human editorial review.
