Recent Advances in the Management of Metastatic Prostate Cancer

Abstract

Management of metastatic prostate cancer has undergone a revolution over the past decade with the introduction of several novel agents and repurposing of others. Several clinical trials reported improved outcomes with the intensification of androgen deprivation therapy by the addition of docetaxel chemotherapy or novel hormonal agents (abiraterone, enzalutamide, or apalutamide) in the metastatic castration-sensitive state. Relugolix has been recently approved as the first oral gonadotropin-releasing hormone receptor antagonist agent with a superior cardiovascular side-effect profile, and serum testosterone suppression compared with a gonadotropin-releasing hormone agonist, leuprolide. Poly-ADP ribose polymerase inhibitors (olaparib and rucaparib) have demonstrated significant clinical benefit for patients harboring deleterious mutations in genes belonging to the homologous recombination repair pathway and have received Food and Drug Administration approval. Recently, lutetium-177-prostate-specific membrane antigen-617 with standard of care treatment has shown to improve overall survival in men with advanced-stage prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer. These recent approvals, successes, and the ongoing investigation of multiple novel agents are expected to continue to dramatically improve survival outcomes of men with metastatic prostate cancer in the coming years.

A Modified Net Reclassification Improvement Statistic

“…Patients with metastatic prostate cancer are by definition high risk. Nevertheless, there is significant variability in the survival times of these patients (Sayegh, Swami, and Agarwal, 2021). Given this heterogeneity, there is a pressing need to identify new biomarkers that can accurately assess patient risk.…”

A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment

“…And even worse, the vast majority of CRPC patients will eventually become resistant to the first-line treatment docetaxel and enzalutamide ( Scott, 2018 ; Lin et al, 2020 ; Moussa et al, 2020 ; Peery et al, 2020 ). In addition, death is usually not caused by the primary tumor but by the formation of distinct metastatic tumors that show resistant properties to varied therapies ( Shore, 2020 ; Sayegh et al, 2021 ). There are unmet clinical needs to tackle drug resistance in PCa through discovering novel chemical entities or certain combinations.…”

Androgen receptor inhibition induces metabolic reprogramming and increased reliance on oxidative mitochondrial metabolism in prostate cancer

“…Prostate cancer progression from localized to advanced metastatic disease is driven by aberrant androgen receptor activity. Therefore, patients with metastatic prostate cancer are treated with androgen deprivation therapies (ADTs), which dampen AR activity by depleting the levels of circulating androgens, alone or in combination with chemotherapy 2 . Prostate cancer that responds to ADT is termed castration-sensitive prostate cancer (CSPC).…”