Second-Line Systemic Therapy for Highly Aggressive Neuroendocrine Prostate Cancer

Abstract

Neuroendocrine prostate cancer (NEPC) is generally an aggressive form of prostate cancer that can arise de novo or develop as a castration-resistant mechanism. While first-line platinum-based chemotherapy is effective against NEPC, its limited response duration and subsequent treatments pose significant clinical challenges. Standard second-line treatments have not been established due to the limited data available. The aim of this review was to reveal the current status of second-line therapy for NEPC. A literature search was conducted using PubMed and Web of Science and a total of 13 articles were included in this review. Prospective and retrospective studies demonstrated that treatment outcome of second-line therapy using platinum with etoposide or docetaxel was unfavorable and progression-free survival was 3 months or shorter. Amrubicin and irinotecan were also frequently used as second-line therapy, however, efficacy of these agents was modest and response duration was less than 6 months. NEPC patients with homologous recombination repair gene alterations may benefit from treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. Ongoing clinical studies investigate various agents, including immune checkpoint inhibitors, molecularly targeted agents, and PARP inhibitors. With the increasing recognition and active biopsy of NEPC lesions, the number of NEPC patients is anticipated to rise. Accumulating more knowledge and experience is crucial in developing novel treatment strategies to combat this disease. Neuroendocrine prostate cancer (NEPC) is often a highly aggressive form characterized by treatment resistance and poor prognosis (1, 2). NEPC is typically treated with cisplatin-based chemotherapy as a standard first-line therapy. However, clinical data on second-line therapy are limited because of its low incidence and the lack of standard therapies. Developing effective second-line and beyond treatments for this highly aggressive cancer is a major clinical challenge. We aimed to review and summarize the oncological outcomes of NEPC patients undergoing second-line systemic therapy. The data used in this article were obtained from PubMed, Web of Science, and Clinical Trials gov.