PSMA-Based Therapy of Metastasized Castrate-Resistant Prostate Cancer

Abstract

Despite clinically established therapeutic regimens, mCRPC patients have a poor prognosis indicating the need for more effective therapies. In recent years, therapeutic radiolabelled PSMA-ligands have shown promising results in therapy of mCRPC patients with favourable safety and efficacy. A positive response to therapy in terms of PSA decline occurs in about 70% of patients; PSA reduction ≥50% is observed in up to 50% of patients. Pain release and improvement of quality of life are observed in a major proportion of symptomatic patients. Preliminary data show that decline of PSA values is accompanied by morphological and/or metabolic changes which can be assessed by CT, bone scintigraphy and/or68Ga-PSMA PET/CT. The most common side effects of RLT are mild fatigue as well as mild and in most cases transient xerostomia. In the majority of studies, no acute or longterm side effects and high-grade haematological or renal toxicity were observed. Even though currently therapeutic PSMA-ligands have not yet been approved,177Lu-PSMA RLT is a promising treatment option to be potentially offered following approved therapies in patients with mCRPC. In the future the use of PSMA-ligands labelled with alpha emitters such as225Ac could be beneficial in patients with compromised bone marrow. Additionally, other novel theranostic agents addressing the gastrin-releasing peptide receptor (GRPR) might be promising treatment options in the future.