Sequencing of Radium-223 and Lutetium-177 Vipivotide Tetraxetan: Maximizing the Benefit of Systemic Targeted Radiation Therapy in Metastatic Castration-Resistant Prostate Cancer
Year: 2025
Type: article
Abstract: 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. 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. 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 (177Lu-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. 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 177Lu-PSMA upon subsequent progression of skeletal metastatic disease and/or the emergence of lymph node or visceral metastases. Graphical abstract available for this article. This summary describes a narrative review on the treatment of men whose prostate cancer has spread beyond the prostate and no longer responds to hormonal therapy (metastatic castration-resistant prostate cancer). Such patients are often treated with intravenous radiopharmaceuticals, which target specific types of tumors or areas of the body. Two radiopharmaceuticals can be used to treat metastatic castration-resistant prostate cancer: radium-223 (Ra-223) and lutetium-177 vipivotide tetraxetan (Lu-177). Currently, each therapy is used once; thus, when the disease no longer responds to initial therapy, an alternative treatment is required. However, owing to the differences in their mechanism of action, Ra-223 and Lu-177 can be used sequentially to extend the duration of disease control. As prostate cancer initially spreads to bones only in 70% of patients, the authors suggest that patients eligible for treatment with radiopharmaceuticals should initially be treated with bone metastases-targeted Ra-223, reserving treatment with prostate-specific membrane antigen-targeted Lu-177 for more progressed disease (that has spread to the bones and/or lymph nodes or visceral organs). Using this approach will allow patients to achieve the longest duration of disease control, maximize treatment benefit, and prolong their quality of life.
Source: Oncology and Therapy
Authors: Samuel Mehr, Ralph Hauke
Institution: Nebraska Cancer Specialists
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,400
OpenAlex ID: W4414929926