Prostate Cancer Treatment: ¹⁷⁷Lu-PSMA-617 Considerations, Concepts, and Limitations

The phase III VISION trial using ¹⁷⁷Lu-PSMA-617 has significant implications for the field of theranostics and broad repercussions for the clinical management of prostate cancer. Metastatic prostate cancer is a rapidly evolving field with a complex landscape that has multiple established therapies, including chemotherapies, hormonal therapies, immunotherapies, radiopharmaceuticals, and targeted therapies. The current landscape was created by an important series of pivotal phase III trials, typically with an overall-survival endpoint. To best understand the VISION trial (performed on patients with metastatic castration-resistant prostate cancer), it is essential to have a thorough understanding of the key decisions that underpinned the design, as well as the context of those decisions. Here, we describe critical elements of the VISION phase III trial and how those elements will shape regulatory decision making and clinic practice. Inclusion and exclusion criteria were carefully crafted, as were treatments, assessments, and endpoints. The results of the VISION trial were impressive, with clear improvements in survival for patients having few treatment alternatives. Besides the significant progress, there are also significant limitations. ¹⁷⁷Lu-PSMA-617 treatments will have far-reaching implications for prostate cancer. Food and Drug Administration approval was granted March 23, 2022, on the basis of the VISION data.