G von Amsberg1, A S Merseburger2. 1. Uroonkologie der Klinik für Onkologie und Hämatologie, Zentrum für Onkologie und der Martini-Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland. g.von-amsberg@uke.de. 2. Klinik für Urologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland.
Abstract
BACKGROUND: For many decades metastatic, castration-resistant prostate cancer (mCRPC) was thought to be treatment inaccessible. However, today, five drugs with significant life-prolonging effects are available in Germany, namely abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. OBJECTIVE: The different treatment strategies in mCRPC are reviewed. MATERIALS AND METHODS: Landmark trials with supplementary information from Medline and abstracts of international congresses (ASCO; ASCO GU, ESMO) are summarized. RESULTS: The androgen receptor (AR)-targeting agents abiraterone and enzalutamide significantly prolong overall survival before and after docetaxel therapy. In addition, cabazitaxel can be applied secondary to docetaxel. Due to the low affinity of cabazitaxel to p‑glycoprotein it remains active even if docetaxel has failed. The α‑emitter radium-223 can be considered in third line therapy for symptomatic patients with bone limited disease only. In patients with castration resistance, a short prostate-specific antigen (PSA) doubling time but without metastases in conventional imaging apalutamide, darolutamide and enzalutamide significantly prolong metastasis-free survival. DISCUSSION: Prostate-specific membrane antigen (PSMA)-ligand therapy and novel targeting agents such as PARP inhibitors are promising new therapeutic modalities for mCRPC. Combination treatment strategies with immunotherapy are currently being evaluated in clinical trials. Based on the results of molecular analyses of tumor tissue as well as of circulating tumor cells and DNA, treatment of prostate cancer will be increasingly personalized in the future.
BACKGROUND: For many decades metastatic, castration-resistant prostate cancer (mCRPC) was thought to be treatment inaccessible. However, today, five drugs with significant life-prolonging effects are available in Germany, namely abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. OBJECTIVE: The different treatment strategies in mCRPC are reviewed. MATERIALS AND METHODS: Landmark trials with supplementary information from Medline and abstracts of international congresses (ASCO; ASCO GU, ESMO) are summarized. RESULTS: The androgen receptor (AR)-targeting agents abiraterone and enzalutamide significantly prolong overall survival before and after docetaxel therapy. In addition, cabazitaxel can be applied secondary to docetaxel. Due to the low affinity of cabazitaxel to p‑glycoprotein it remains active even if docetaxel has failed. The α‑emitter radium-223 can be considered in third line therapy for symptomatic patients with bone limited disease only. In patients with castration resistance, a short prostate-specific antigen (PSA) doubling time but without metastases in conventional imaging apalutamide, darolutamide and enzalutamide significantly prolong metastasis-free survival. DISCUSSION: Prostate-specific membrane antigen (PSMA)-ligand therapy and novel targeting agents such as PARP inhibitors are promising new therapeutic modalities for mCRPC. Combination treatment strategies with immunotherapy are currently being evaluated in clinical trials. Based on the results of molecular analyses of tumor tissue as well as of circulating tumor cells and DNA, treatment of prostate cancer will be increasingly personalized in the future.
Authors: William Lopez; Nhu Nguyen; Jessica Cao; Christine Eddow; K Kirk Shung; Nan Sook Lee; Mosses S S Chow Journal: Technol Cancer Res Treat Date: 2021 Jan-Dec