Radioligand therapy with lutetium-177-PSMA in metastatic castration-resistant prostate cancer with bone involvement: a comprehensive review

Background: Prostate cancer (PCa) with bone metastases is one of the most aggressive forms of the disease, accompanied by severe pain, decreased quality of life (QOL), and limited treatment options. Standard treatments, including androgen deprivation therapy and chemotherapy (CT), are often insufficiently effective in advanced stages, necessitating the search for new targeted approaches.

Objective: Systematization of the current data on prostate-specific membrane antigen (PSMA)-targeted theranostics, with a focus on radioligand therapy with ¹⁷⁷Lu-PSMA-617, and analysis of the clinical efficacy, safety profile, and promising development directions for this method.

Methods: A review of publications in PubMed, Scopus, and Web of Science was conducted, including key clinical trials (VISION, TheraP, PSMAfore). Data on survival, biochemical response, patient selection criteria, and toxicity profile were examined.

Results: Radioligand therapy with ¹⁷⁷Lu-PSMA-617 demonstrated significant improvements in overall survival, time without radiological progression, and biochemical response rate compared with standard treatment and chemotherapy. The most common adverse events were xerostomia and mild to moderate hematologic toxicity. The use of PSMA-PET/CT proved to be a key tool for patient selection, with higher PSMA expression correlating with better treatment outcomes. Promising development areas include combinations with PARP inhibitors and the use of α-emitting radiopharmaceuticals (²²⁵Ac-PSMA).

Conclusion: Therapy with ¹⁷⁷Lu-PSMA-617 represents a breakthrough in the treatment of prostate cancer with bone metastases, demonstrating significant improvements in survival and quality of life. The inclusion of radioligand therapy at earlier stages and the development of combination strategies open up new prospects for personalized oncourology.