Comparative outcomes of [^177Lu]Lu-PSMA-617 versus radium-223 in bone-metastatic castration-resistant prostate cancer: A real-world propensity-matched analysis.

Abstract

e17070 Background: Two guideline-recognized radiopharmaceuticals differ in mechanism and indication. Radium-223 (Ra-223), an alpha-emitter targeting osteoblastic lesions, and Lu-PSMA-617, a PSMA-targeted beta-emitter active in bone and soft-tissue metastases; both improved survival in their respective pivotal trials. Lu-PSMA-617 received FDA approval for taxane-naïve mCRPC after ARPI progression (PSMAfore). Despite these advances, no head-to-head data exist. Clinicians often choose between Ra-223 and Lu-PSMA-617 for mCRPC when chemotherapy is unsuitable. Methods: We conducted a retrospective study using the TriNetX Network of adult men with prostate cancer and bone metastases who received Lu-PSMA-617 or Ra-223. Castration resistance was approximated by ongoing ADT and prior ARPI. Patients with visceral metastases were excluded. Outcomes were assessed at 3, 6 & 12 months. Survival was analyzed with Kaplan–Meier methods, log-rank tests, and Cox models to derive hazard ratios (HR) with 95% CI. Results: At 3 months, mortality was substantially lower with Lu-PSMA-617 (HR 0.34, 95% CI 0.18–0.6, p = 0.001). Hospitalization was also reduced (HR 0.46, p = 0.035). Ra-223 patients had higher rates of severely elevated PSA levels (≥50 ng/mL), yielding (HR 0.57, p = 0.07).At 6 months, the survival benefit persisted (HR 0.37, 95% CI 0.25–0.56, p < 0.001). Hospitalizations were again fewer with Lu-PSMA-617 (HR 0.47, p = 0.009). ER visits did not differ significantly (HR 0.65, p = 0.199). PSA outcomes favored Lu-PSMA-617 (HR 0.57, p = 0.025). Hematologic safety endpoints were neutral.At 1 year, Lu-PSMA-617 demonstrated a marked survival benefit (HR 0.46, 95% CI 0.35–0.61, p < 0.001). Hospitalizations were fewer with Lu-PSMA-617 (HR 0.56, p = 0.01). ER visits were similar between groups (HR 1.04, p = 0.71). Rates of PSA ≥50 ng/mL were less frequent in the Lu-PSMA-617 group (HR 0.56, p = 0.006). Hematologic outcomes remained neutral. Conclusions: In this real-world propensity-matched analysis, Lu-PSMA-617 was associated with superior survival and fewer hospitalizations compared with Ra-223 in bone-metastatic mCRPC. While Ra-223 remains a preferred option per NCCN for symptomatic bone-predominant disease without visceral metastases, our findings suggest that when PSMA-avid disease is present, Lu-PSMA-617 should be prioritized as the radiopharmaceutical of choice. Prospective studies are warranted to confirm optimal sequencing.