A Phase 2 Trial of Radium²²³ and Stereotactic Ablative Radiation Therapy in Hormone-Naïve Men with Oligometastatic...

We hypothesized that treatment with Radium²²³ (Ra²²³) and Stereotactic ablative radiotherapy (SABR) in patients with bone-only metachronous oligometastastic hormone-sensitive prostate cancer (moHSPC) could safely delay the start of androgen deprivation therapy (ADT) and maintain quality of life (QoL).

This prospective trial included 20 men with moHSPC and ≤5 bone-only metastases who previously had definitive treatment to the prostate and pelvic lymph nodes. Eligibility criteria were testosterone ≥ 100 ng/dL and metastases validated by conventional imaging. Exclusion criteria were postinitial treatment (LHRH) therapy or N1 disease at bone metastasis diagnosis. Treatment included 6 cycles of Ra²²³ and SABR (30 Gy in 5 fractions). Bone scans and Prostate Specific Antigen (PSA) levels were monitored regularly. The primary endpoint was freedom from ADT use at 15 months in ≥20% of patients. Patients were followed for 2 years, with clinically significant patient-reported outcome changes defined as >1/2 standard deviation from baseline. Statistical analyses used Wilcoxon rank sum, Pearson's χ² tests, and univariate Cox regression, with significance set at P < .05 RESULTS: The median number of Ra²²³ cycles was 6. Freedom from ADT at 15 and 24 months was 50.0% and 40.0%, respectively (P < .001). Eleven (55%) and 5 (25%) patients had PSA declines exceeding 50% and 90%, respectively, with 2 patients achieving undetectable PSA levels (<0.01) at 2 years. No significant changes were observed in any patient-reported outcome QoL domains. Two patients had grade 3 skeletal-related events, and grade 2+ events attributed to Ra²²³ and SABR were observed in 4 and 2 patients, respectively.

In this phase 2 trial, the initial use of Ra²²³ and SABR for moHSPC significantly delayed ADT use compared with historical controls. The therapy is well tolerated, preserves QoL, and can lead to undetectable PSA levels at 2 years.