The Strategy to Initiate PSMA-Based Therapies for Advanced Prostate Cancer

Ching-Chu LuTaiwan Speaker The Strategy to Initiate PSMA-Based Therapies for Advanced Prostate CancerPSMA-targeted radioligand therapy (PSMA RLT) has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), particularly after failure of androgen deprivation therapy, next-generation hormonal agents, and chemotherapy. While PSMA RLT is currently a third-line treatment, evidence from the PSMAfore trial suggests its potential efficacy when used earlier in the treatment sequence, prior to chemotherapy, offering a new strategy for improving progression-free survival (PFS) in mCRPC patients. In addition, PSMA RLT is being explored in metastatic hormone-sensitive prostate cancer (mHSPC), with ongoing trials such as PSMAddition, investigating its role in delaying disease progression and improving patient outcomes when combined with standard therapies. Moreover, PSMA RLT is being evaluated in combination with other treatments, including PARP inhibitors, immunotherapy, chemotherapy, and radiation therapy. Numerous ongoing trials are exploring these combination therapies to further enhance the therapeutic efficacy of PSMA RLT and improve patient outcomes in advanced prostate cancer. Novel radionuclides such as Actinium-225 (Ac-225) and Terbium-161 (Tb-161) are being investigated for their potential to improve the therapeutic profile of PSMA RLT. These isotopes offer unique advantages, including different radiation characteristics that could increase the efficacy and safety of PSMA-targeted therapies. In conclusion, PSMA RLT is becoming a cornerstone of precision oncology for prostate cancer. As research continues to explore its use earlier in the treatment continuum, in combination with other therapies, and with the incorporation of novel radionuclides, PSMA RLT holds great promise for improving outcomes in advanced prostate cancer patients.