Metastatic Prostate Cancer: Treatment Options

Abstract

<b><i>Background:</i></b> Metastatic prostate cancer (PCa) is associated with considerable diminished overall survival (OS). Standard treatment for metastatic PCa has long been androgen deprivation therapy alone, with patients initially responding to this treatment and then progressing to a castration-resistant phase. <b><i>Summary:</i></b> The advent of novel therapeutic agents has changed this paradigm, with high-level evidence that upfront combination therapy with either docetaxel or new hormonal agents results in improved OS for patients with metastatic hormone-sensitive PCa. In the absence of a comprehensive clinical trial investigating the comparative efficacy and safety of all agents, clinicians are responsible for choosing the most appropriate therapy in close coordination with patients. Furthermore, the same therapeutic agents are also efficient in the castration-resistant phase, leading to the issue of the best therapeutic sequence. Finally, along with systemic therapy and molecular imaging advancements, radiotherapy was investigated in the oligometastatic setting, whether it is to treat the primary tumour or metastases. <b><i>Key Messages:</i></b> In this complex landscape, where providers have multiple effective therapeutic options to treat metastatic PCa patients, priority must be given to determine which treatment combination and sequence is best suited to a particular patient, given his comorbidities and preferences.

MiR-182-5p Modulates Prostate Cancer Aggressive Phenotypes by Targeting EMT Associated Pathways

“…In DU145 cells treated with docetaxel, the ectopic expression of miR-182-5p led to a significant increase in cell viability when compared to the negative control. Docetaxel is the first line of treatment for patients with advanced prostate cancer patients, including the ones with the metastatic castration-resistant form of the disease [ 48 , 49 , 50 ]. However, approximately 30% of the patients present primary resistance to this drug, and over time even the ones that initially responded develop resistance [ 51 , 52 ].…”

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

“…Radical prostatectomy and radiotherapy with or without androgen-deprivation therapy (ADT) are the standard curative treatments for localized PCa [ 2 , 3 ], while ADT remains the mainstay therapy for advanced disease. Metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) PCa [ 2 , 3 ] represent, however, a major clinical challenge, and several types of treatments, including androgen receptor targeting inhibitors (ARTi), chemotherapies, radioligands, and PARP inhibitors, have been investigated to improve patient survival [ 4 ].…”

The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer

“…In the United States, prostate cancer is the second leading cause of cancer-related death in men, projected to have 268,490 new cases and 34,500 deaths in 2022 [ 2 ]. Although localized prostate cancer may be successfully treated with radical prostatectomy or radiotherapy [ 3 ], standard androgen deprivation therapy (ADT) followed by chemotherapy (Taxanes), androgen synthesis inhibitor (abiraterone), or androgen receptor (AR) antagonists (enzalutamide, apalutamide, and darolutamide) remains the primary treatment option for patients with advanced prostate cancer [ 4 ]. Unfortunately, despite initial response to the current therapy, all patients eventually will develop from castration-resistant prostate cancer (CRPC) to drug-resistant CRPC through androgen-dependent or androgen-independent mechanisms.…”