How Will PSMAddition Impact the Management of Prostate Cancer?

The upfront treatment of metastatic prostate cancer consists of androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI), with or without the addition of docetaxel or a poly(ADP-ribose) polymerase (PARP) inhibitor. ¹⁷⁷Lu-PSMA-617 has demonstrated efficacy in androgen pathway modulator-resistant disease, though earlier use might improve efficacy prior to the development of radioresistant or prostate-specific membrane antigen (PSMA)-low clones. In the phase 3 PSMAddition trial, first-line ¹⁷⁷Lu-PSMA-617 added to ADT + ARPI improved radiographic progression-free survival versus ADT + ARPI alone. Further research could better elucidate the impact on health care costs, quality of life, and other long-term implications of the earlier integration of this radionuclide therapy. PATIENT SUMMARY: Patients who have prostate cancer that has spread should generally receive a minimum of dual hormonal therapies. Targeted radionuclide therapy involves the injection of a radioactive particle into blood that is delivered preferentially to target cells (usually tumor cells). The PSMAddition trial demonstrated longer cancer control when this therapy is added to double hormonal therapy for the initial treatment of metastatic disease, with common side effects of dry mouth, fatigue, gastrointestinal issues, and low blood counts.