Early-access Use of Radioligand Therapy in Prostate Cancer

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) has transformed the management of metastatic castration-resistant prostate cancer. Early-access programs conducted before full regulatory approval provide important real-world evidence complementing clinical trials. Across heterogeneous and often heavily pretreated populations, lutetium-177 PSMA-617 demonstrated consistent clinical benefit, with a tolerable safety profile. Key predictors of poorer outcomes include low PSMA expression, discordant imaging phenotypes, liver metastases, and impaired performance status. These programs refined patient selection and response assessment, highlighting the value of PSMA positron emission tomography over prostate-specific antigen alone, and informed strategies such as extended treatment and dosimetry-guided care. They also enabled early evaluation of α-emitter therapies. PATIENT SUMMARY: Recent years have seen the approval of radioligand therapy (RLT) for patients with advanced metastatic prostate cancer. Our mini review focuses on results in early-access programs. These findings support the effectiveness and manageable safety of RLT in routine practice, including in more complex cases that are often excluded from trials.