madman
Super Moderator
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.
INTRODUCTION
In 2021, it is estimated that 26% of new noncutaneous cancer cases will be because of prostate cancer resulting in 11% of cancer-related deaths in the United States, making it the most common malignancy in men and the second leading cause of cancer mortality.1 Following the onset of metastatic disease, the disease is invariably fatal with a 5-year survival rate of only 30%. Furthermore, the incidence of metastatic prostate cancer seems to have increased in all races and age groups over the past decade.
*Herein, we discuss the most recent advances in the management of metastatic prostate cancer and highlight recently approved agents and ongoing clinical trials. We will review the mechanism of action of recently approved agents (Table 1; Fig 1). We also present principles for optimal therapy selection based on clinical and molecular criteria, current roadblocks regarding treatment intensification in the castrate-sensitive stage, and challenges with treatment sequencing. Finally, we summarize promising therapies currently under development
*METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER
Recent Approvals
Ongoing Investigations
*METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Recent Approvals
Ongoing Investigations
*SELECTION OF PATIENTS
Metastatic Castration-Sensitive Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
*CHALLENGES AND FUTURE DIRECTIONS
In conclusion, an extraordinary pace of drug development and approvals have revolutionized the treatment paradigm of metastatic prostate cancer over the past decade. The current era of targeted therapy, immunotherapy, theranostics, and the overall treatment of advanced prostate cancer will continue to evolve rapidly, and further improvements in survival outcomes are expected in the coming years. These advancements in therapeutics will also pose new challenges in the clinic in terms of treatment selection and sequencing of therapies, and will increasingly require additional studies that focus on optimization of outcomes and minimization of cost and toxicities.
INTRODUCTION
In 2021, it is estimated that 26% of new noncutaneous cancer cases will be because of prostate cancer resulting in 11% of cancer-related deaths in the United States, making it the most common malignancy in men and the second leading cause of cancer mortality.1 Following the onset of metastatic disease, the disease is invariably fatal with a 5-year survival rate of only 30%. Furthermore, the incidence of metastatic prostate cancer seems to have increased in all races and age groups over the past decade.
*Herein, we discuss the most recent advances in the management of metastatic prostate cancer and highlight recently approved agents and ongoing clinical trials. We will review the mechanism of action of recently approved agents (Table 1; Fig 1). We also present principles for optimal therapy selection based on clinical and molecular criteria, current roadblocks regarding treatment intensification in the castrate-sensitive stage, and challenges with treatment sequencing. Finally, we summarize promising therapies currently under development
*METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER
Recent Approvals
Ongoing Investigations
*METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Recent Approvals
Ongoing Investigations
*SELECTION OF PATIENTS
Metastatic Castration-Sensitive Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
*CHALLENGES AND FUTURE DIRECTIONS
In conclusion, an extraordinary pace of drug development and approvals have revolutionized the treatment paradigm of metastatic prostate cancer over the past decade. The current era of targeted therapy, immunotherapy, theranostics, and the overall treatment of advanced prostate cancer will continue to evolve rapidly, and further improvements in survival outcomes are expected in the coming years. These advancements in therapeutics will also pose new challenges in the clinic in terms of treatment selection and sequencing of therapies, and will increasingly require additional studies that focus on optimization of outcomes and minimization of cost and toxicities.
