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

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 [ 177 Lu]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 [ 177 Lu]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 [ 177 Lu]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 [ 177 Lu]Lu‐PSMA‐RLT as a viable treatment option for this challenging population.