Castration resistant prostate cancer: from existing therapies to compounds under investigation

Prostate carcinoma is a highly prevalent biologically and clinically heterogeneous disease. Unfortunately, within 5 years of diagnosis, 10-20% of patients acquire a castration-resistant prostate cancer (CRPC) in spite of multiple surgical and non-surgical therapy choices. The clinical context of CRPC is heterogeneous, encompassing patients with asymptomatic prostate-specific antigen (PSA) elevation following ADT failure and good performance status, as well as those experiencing severe, incapacitating symptoms and a rapidly progressing disease that ultimately results in death. Non-metastatic CRPC (nmCRPC) is a stage of the disease that is transient and is defined by certain criteria that are set within a certain time frame. Most patients with nmCRPC will eventually develop metastatic lesions, which are linked to morbidity and death specific to prostate cancer. Until 2010, the only treatments for patients with metastatic prostate cancer were androgen deprivation therapy and docetaxel. The advent of several hormonal and non-hormonal therapies such as abiraterone acetate, enzalutamide, apalutamide, cabazitaxel, darolutamide, the immunotherapeutic sipuleucel-T has brought about a paradigm shift in management of CRPC patients. These molecules have demonstrated a survival benefit in mCRPC & nmCRPC. For patients with advanced PSMA-positive mCRPC, 177Lu-PSMA-617 radioligand therapy offers a novel and efficacious therapeutic approach. PARPi are sensitive to tumors with gene mutations that impact homologous recombination repair, such as BRCA1 and BRCA2 abnormalities in mCRPC. The goal of this study was to highlight recent developments in CRPC clinical trials as well as guidelines recommendations for CRPC.