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Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (¹⁷⁷Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of ¹⁷⁷Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of ¹⁷⁷Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of ¹⁷⁷Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.