Sequencing of Radium-223 and Lutetium-177 Vipivotide Tetraxetan: Maximizing the Benefit of Systemic Targeted Radiation Therapy in Metastatic Castration-Resistant Prostate Cancer

Introduction: The goals of treatment for metastatic castration-resistant prostate cancer are disease management, improving quality of life, and prolonging life. Although androgen-receptor blockade and chemotherapy can control the disease for several years in most patients, resistance to treatment and continued disease progression are inevitable. Radionuclides have emerged as important tools in the therapeutic arsenal against prostate cancer. Appropriate sequencing with existing standards of care is paramount to ensure that patients get the maximum clinical benefit from as many life-prolonging therapies as possible during the treatment journey.

Methods: We review radionuclide therapy for men with metastatic castration-resistant prostate cancer and present a treatment algorithm used in our specialist center to provide optimal care.

Results: The goal of the treatment algorithm employed in our specialist center is to provide optimal patient care by using and sequencing appropriate systemic radionuclide therapy. The first step is to determine the extent of disease and metastases to offer personalized treatment to extend survival. Appropriate treatment sequencing can allow men to receive the life-prolonging benefits of radium-223 immediately upon bone-only progression, while remaining eligible to benefit from chemotherapy and/or lutetium-177 vipivotide tetraxetan ( 177 Lu-PSMA) upon further disease progression. Importantly, although prostate-specific antigen (PSA) is frequently perceived as a marker for prostatic disease burden, survival benefits of radionuclide therapy may be independent of change in PSA.

Conclusions: As the majority of men with metastatic castration-resistant prostate cancer first present with bone-only metastases, they may be treated initially with radium-223, while still remaining eligible to benefit from chemotherapy and 177 Lu-PSMA upon subsequent progression of skeletal metastatic disease and/or the emergence of lymph node or visceral metastases. Graphical abstract available for this article.

Indexed on Europe PMC as PubMed record 41060609 (DOI 10.1007/s40487-025-00377-9). Its title names Lutetium-177 vipivotide tetraxetan and its text names Prostate cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea "Alpha-emitting PSMA therapy at first metastatic diagnosis" and no figure has been checked by an editor.