The 177Lu-PSMA-617 PRLT “Superresponders” Among Metastatic Castration-Resistant Prostate Carcinoma (mCRPC) with Extensive Disease: Case Series with Review of Literature on PSMA-Based Theranostics in the Therapeutic Armamentarium of mCRPC

Abstract The incidence of prostate cancer is increasing worldwide, leading to a growing prevalence of metastatic castration-resistant prostate cancer (mCRPC), which is characterized by treatment resistance and poor prognosis, often posing a challenging clinical setting. Treatment approach to mCRPC necessitates multimodal strategies, including cytotoxic chemotherapy, novel hormonal agents, and targeted therapies. Prostate cancer cells show upregulation of prostate-specific membrane antigen (PSMA), making it an excellent molecular target for radioligand therapy (PRLT). The β-emitting radioisotope lutetium-177 (177Lu), linked to PSMA-targeting ligands, has recently gained prominence as a promising and well-tolerated therapeutic option, demonstrating minimal adverse effects. Recent studies have demonstrated its efficacy in improving survival, delaying disease progression, and enhancing quality of life in patients with mCRPC. We illustrate here two cases of mCRPC with extensive disease burden, both demonstrating remarkable responses to 177Lu-PSMA-617 PRLT following progression on hormonal therapy and chemotherapy, highlighting its therapeutic potential in advanced-stage disease. A brief review has been made on the recently completed and ongoing clinical trials in this domain.