Background: Radioligand therapy with [177Lu]Lu-PSMA-617 represents an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). Its clinical positioning relative to standard therapies remains under discussion. Objective: To compare overall survival (OS), radiographic progression-free survival (rPFS), PSA response, and treatment burden across randomised trials evaluating [177Lu]Lu-PSMA-617 versus androgen receptor pathway inhibitors (ARTA), Cabazitaxel, or standard of care (SOC). Evidence Acquisition: We conducted a meta-analysis of five randomised controlled trials, including 2073 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed survival endpoints, baseline comparability, and treatment intensity. Evidence Synthesis: [177Lu]Lu-PSMA-617 significantly improved rPFS and PSA response. While modest overall, the OS benefit was more pronounced in taxane-naïve populations. Compared with Cabazitaxel, [177Lu]Lu-PSMA-617 was associated with similar or better survival despite shorter treatment duration and potentially lower cumulative toxicity and cost. Economic modelling suggests it could offer a more sustainable therapeutic option under typical willingness-to-pay thresholds. Conclusions: [177Lu]Lu-PSMA-617 shows clinical effectiveness and economic value in mCRPC, with potential advantages over Cabazitaxel and ARTA. Its use could be prioritised in early treatment lines. Patient Summary: This study suggests that PSMA-targeted radioligand therapy is at least as effective as other treatments for advanced prostate cancer, with potential benefits in terms of toxicity, duration, and overall cost.
背景：放射性配体疗法[¹⁷⁷Lu]Lu-PSMA-617是转移性去势抵抗性前列腺癌（mCRPC）的一种新兴治疗手段。其相对于标准疗法的临床定位仍在探讨中。目的：通过随机试验比较[¹⁷⁷Lu]Lu-PSMA-617与雄激素受体通路抑制剂（ARTA）、卡巴他赛或标准治疗（SOC）在总生存期（OS）、影像学无进展生存期（rPFS）、PSA应答及治疗负担方面的差异。证据获取：我们对五项随机对照试验进行了荟萃分析，共纳入2073例PSMA阳性转移性去势抵抗性前列腺癌（mCRPC）患者。评估了生存终点、基线可比性及治疗强度。证据综合：[¹⁷⁷Lu]Lu-PSMA-617显著改善了rPFS和PSA应答。虽然总体OS获益有限，但在未接受紫杉类药物治疗的人群中更为显著。与卡巴他赛相比，[¹⁷⁷Lu]Lu-PSMA-617尽管治疗持续时间较短，但具有相似或更优的生存获益，且累积毒性和成本可能更低。经济模型表明，在典型的支付意愿阈值下，该疗法可能提供更具可持续性的治疗选择。结论：[¹⁷⁷Lu]Lu-PSMA-617在mCRPC治疗中显示出临床有效性和经济价值，相较于卡巴他赛和ARTA具有潜在优势。可考虑在早期治疗线中优先使用。患者总结：本研究表明，PSMA靶向放射性配体疗法对晚期前列腺癌的疗效至少不亚于其他治疗，且在毒性、治疗持续时间和总成本方面具有潜在优势。
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