Novel treatment options in the management of metastatic castration-naïve prostate cancer; which treatment modality to choose?

Abstract

Androgen-deprivation therapy (ADT) has been the mainstay of treatment of metastatic prostate cancer since the first report of its hormonal dependence in the 1940s. Since 2015, the addition of docetaxel and the addition of abiraterone to ADT have conferred substantial overall survival benefit in men with metastatic castration-naïve prostate cancer (mCNPC). The shift of these treatment options for metastatic prostate cancer from the castration-resistant setting to the castration-naïve setting has led to new challenges in the management of this disease. It remains to be determined which patients may benefit most from either early concomitant docetaxel or from abiraterone with ADT, since biomarkers for early therapy response and risk stratification are currently lacking. Therefore, the ability to personalize medicine is hampered. Furthermore, the earlier detection of metastatic prostate cancer by using new imaging modalities makes the application of clinical trial results in daily practice increasingly challenging. Recently, both local radiotherapy to the primary tumor combined with ADT and abiraterone combined with ADT showed a survival benefit in low-volume disease patients. The latest data also demonstrated a survival benefit with the addition of apalutamide or enzalutamide to ADT. The extent of metastatic disease may become one of the most important factors to determine treatment choice. In this review article, we summarize trial data to provide guidance for treatment selection in metastatic castration-naïve prostate cancer.

A Shoulder Mass Revealing a Metastatic Prostate Cancer

“…In addition to symptomatic treatment, metastatic prostate cancer is treated with chemotherapy and ADT [5].…”

“…Bone is the third most common metastatic site after the lung and liver [4]. Treatment is based on ADT combined with second-generation hormone therapy or docetaxel chemotherapy [5]. Some studies show a benefit of local treatment in selected presenting metastatic and hormone-sensitive prostate cancer [6] [7] [8].…”

Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

“…Based on the identified hormone-related tumor growth, the first treatments consisted in androgen-deprivation therapy. Currently, the therapeutical options have evolved by associating chemotherapy, radiotherapy and immunotherapy, depending on the tumor, patient or drug side effects (12)(13)(14). The challenges encountered by the endocrine therapy in prostate cancer are depicted in Figure 3; one important finding is that a Western diet rich in long chain fatty acids may promote prostate cancer to lethal stages (15).…”

Mechanistic Insights into the Selective Dual BET and PLK1 Inhibitory Activity of a Novel Benzamide Compound in Castration‐Resistant Prostrate Cancer

“…[10 -13] Treatment options have been a challenge with research on co-administration therapy of clinically approved drugs under investigation. [14] Molecular targets identification with underlying mechanism involved in carcinogenesis of the prostate as well as optimization of androgenic suppression in the later stages of CRPC is key to the development of new drugs. [15] The Bromodomain and extra-terminal domain (BET) protein family consists of a group of proteins that specializes in recognizing acetylated lysine on chromatin.…”

“…In light of this, several other treatment regimens have been adopted over the years which include the use of docetaxel, abiraterone, and radium‐223 [10–13] . Treatment options have been a challenge with research on co‐administration therapy of clinically approved drugs under investigation [14] …”