Sequential use of targeted radioligand therapies in metastatic castration-resistant prostate cancer: A case report and systematic review.

[BACKGROUND] The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has evolved with the introduction of novel therapies, including targeted radioligand therapies (RLTs). However, data about sequential use of RLT remains limited.

[OBJECTIVE] This study aims to present a case report on the sequential use of RLTs and to investigate the efficacy of administering different RLTs in sequence.

[METHODS] A systematic review of the literature was conducted following PRISMA guidelines. Studies reporting on patients who received sequential RLT agents for mCRPC and included efficacy data for the subsequent agent were included in the study.

[RESULTS] A total of 16 studies met the inclusion criteria. Among these, nine studies reported the use of Lutetium-177 PSMA (¹⁷⁷Lu‑PSMA) following Radium-223 (Ra), seven studies reported Actinium‑225 PSMA (²²⁵Ac‑PSMA) after ¹ ⁷⁷Lu‑PSMA, two studies reported ²²⁵Ac‑PSMA following Ra, and one study investigated Terbium-161 PSMA (¹⁶¹Tb‑PSMA) after ¹ ⁷⁷Lu‑PSMA. For patients receiving ¹ ⁷⁷Lu‑PSMA following Ra, the reported median progression-free survival (PFS) ranged from 3 to 10 months, while overall survival (OS) ranged from 11.1 to 18 months. In those treated with ²²⁵Ac‑PSMA after prior ¹ ⁷⁷Lu‑PSMA, the median PFS ranged from 3.1 to 10 months, and OS ranged from 7.7 to 16 months. Treatment was generally well tolerated; hematologic toxicities were the most reported adverse events.

[CONCLUSION] Sequential administration of RLTs may provide sustained clinical benefit in patients with mCRPC. However, the existing evidence is limited, heterogeneous, and predominantly derived from retrospective analyses.