Ruder Samuel, Ricaurte-Fajardo Andres, Sun Michael, Huicochea Castellanos Sandra, Osborne Joseph R, Tagawa Scott T
Department of Medicine, Division of Hematology and Oncology, New York Presbyterian Weill Cornell Medical Center, 520 East 70th Street, Starr Pavilion, NY, NY, 10065, USA.
Department of Radiology, Division of Molecular Imaging and Therapeutics, Weill Cornell Medicine, New York, NY, USA.
Curr Treat Options Oncol. 2025 Apr;26(4):291-301. doi: 10.1007/s11864-025-01296-7. Epub 2025 Mar 26.
Prostate-specific membrane antigen targeted radionuclide therapies (PSMA-TRT) such as 177Lu-PSMA-617 hold great promise in improving clinical outcomes at various stages of prostate cancer. The FDA approval of 177Lu-PSMA-617 represents a significant advancement in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The VISION trial demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) with 177Lu-PSMA-617 in patients with mCRPC who had already receive androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy. Exploration of 177Lu-PSMA-617 in earlier stages of prostate cancer, such as in the PSMAfore trial for patients who have not received chemotherapy, holds great promise for improving long-term outcomes and delaying exposure to chemotherapy. Combining 177Lu-PSMA-617 with other therapies, including chemotherapy, PARP inhibitors, and immunotherapy, is an area of active investigation. This review will also discuss alternative radionuclides (such as actininum-225 and terbium-161) and delivery vehicles (such as PSMA-I&T), which we find promising. Predictive biomarkers and dosimetry will be crucial for identifying patients most likely to benefit from PSMA-TRT. Continued research and refinement of these therapies will lead to PSMA-targeted treatments becoming an integral part of prostate cancer management.
前列腺特异性膜抗原靶向放射性核素疗法（PSMA-TRT），如177Lu-PSMA-617，在改善前列腺癌各个阶段的临床结局方面具有巨大潜力。美国食品药品监督管理局（FDA）批准177Lu-PSMA-617代表了转移性去势抵抗性前列腺癌（mCRPC）治疗的重大进展。VISION试验表明，在已接受雄激素受体通路抑制剂（ARPI）和紫杉烷化疗的mCRPC患者中，177Lu-PSMA-617可改善影像学无进展生存期（rPFS）和总生存期（OS）。在前列腺癌的早期阶段探索177Lu-PSMA-617，例如在未接受化疗的患者的PSMAfore试验中，对于改善长期结局和延迟化疗暴露具有很大前景。将177Lu-PSMA-617与其他疗法（包括化疗、PARP抑制剂和免疫疗法）联合使用是一个积极研究的领域。本综述还将讨论我们认为有前景的替代放射性核素（如锕-225和铽-161）和递送载体（如PSMA-I&T）。预测性生物标志物和剂量测定对于识别最有可能从PSMA-TRT中获益的患者至关重要。对这些疗法的持续研究和改进将使PSMA靶向治疗成为前列腺癌管理的一个组成部分。
