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. 2025 Dec;21(6):639-646.
doi: 10.1111/ajco.14195. Epub 2025 May 29.

Safety and Efficacy of Lutetium-177 PSMA Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Metastases (Asian Population Study)

Cherie Wei Qi Ng  1 , Wei Ming Chua  2   3   4 , Winnie Wing-Chuen Lam  2   3 , Aaron Kian-Ti Tong  2   3 , David Chee Eng Ng  2   3 , Charlene Yu Lin Tang  2   3 , Wei Ying Tham  2   3 , Ravindran Kanesvaran  3   5 , Alvin Seng Cheong Wong  6 , Kae Jack Tay  3   7 , Kenneth Chen  3   7 , Sue Ping Thang  2   3
Affiliations

Safety and Efficacy of Lutetium-177 PSMA Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Metastases (Asian Population Study)

Cherie Wei Qi Ng et al. Asia Pac J Clin Oncol. 2025 Dec.

Abstract

Introduction: Prostate cancer is the second most common cancer and the leading cause of cancer-related deaths in men. Patients with metastatic castration-resistant prostate cancer (mCRPC) with diffuse bone metastases have limited treatment options due to severe hematological toxicity risks. This study evaluates the safety and efficacy of [177Lu]Lu-PSMA radioligand therapy (RLT) in this high-risk group within an Asian population.

Methods: We conducted a retrospective analysis of 48 mCRPC patients with PSMA-avid diffuse bone metastases treated with [177Lu]Lu-PSMA-RLT between May 9, 2018 and Jan 10, 2023. Patients received up to 4 to 6 initial therapy cycles, with additional cycles considered for those who responded initially but later progressed. Primary and secondary endpoints included overall survival (OS), PSA progression-free survival (PFS), PSA response, clinical response, and toxicity assessment.

Results: Median OS was 9.3 months. Any PSA response was observed in 75% of patients. Notably, 48% achieved a ≥50% PSA reduction, correlating with a longer median OS (11.6 vs. 8.6 months, p = 0.03). Median PSA PFS was 3.2 months, with improved outcomes observed in patients achieving ≥50% PSA reduction (6.0 vs. 1.8 months, p < 0.0001). Pain relief was reported in 43% of patients, with a median pain score reduction of 5 points. The most common adverse effect was hepatotoxicity, with anemia in 27%, neutropenia in 27%, and thrombocytopenia in 21%.

Conclusion: [177Lu]Lu-PSMA-RLT demonstrates clinically meaningful benefits in survival and symptom management with an acceptable safety profile for mCRPC patients with extensive bone metastases. These findings support [177Lu]Lu-PSMA-RLT as a viable treatment option for this challenging population.

Keywords: diffuse bone metastases; lutetium‐177 PSMA; mCRPC; prostate cancer; radioligand therapy.

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