Current treatment options for newly diagnosed metastatic hormone-sensitive prostate cancer—a narrative review

Abstract

Prostate cancer continues to be one of the most commonly diagnosed cancers in men globally and a leading cause of male cancer deaths. The landscape of metastatic hormone-sensitive prostate cancer has significantly changed over the past decade. For many years, androgen deprivation therapy alone through surgical or chemical castration was the mainstay of treatment yielding limited 5-year survival rates. New treatment approaches using Docetaxel chemotherapy or androgen receptor pathway inhibitors to intensify upfront systemic therapy have resulted in significantly improved survival rates compared to androgen deprivation therapy alone. Clinicians are now equipped with an arsenal of drugs capable of prolonging life for metastatic hormone-sensitive prostate cancer patients. Furthermore, new treatment modalities are being tested in clinical trials making treatment of metastatic hormone-sensitive prostate cancer an extremely dynamic space. In this narrative review, we provide an overview of the key systemic treatments for metastatic hormone-sensitive prostate cancer, namely androgen deprivation therapy, novel androgen receptor pathway inhibitors and Docetaxel. We summarise a series of landmark trials that have led to the integration of novel androgen receptor pathway inhibitors and docetaxel into the treatment paradigm for metastatic hormonesensitive prostate cancer. Lastly, we discuss nursing, financial and side-effect considerations pertaining to the use of these drugs. This article aims to give its readers an understanding of the evidence and clinical aspects of novel therapies in metastatic hormone-sensitive prostate cancer as they become increasingly available for use around the world.

Distant Nodes Seen on PSMA PET-CT Staging Predicts Post-Treatment Progression in Men with Newly Diagnosed Prostate Cancer—A Prospective Cohort Study

“…Distant nodes seen on PSMA PET-CT was found to be the only statistically significant predictor of treatment progression. These findings could imply that the detection of distant nodes allowed intensification of upfront therapy (chemotherapy or ARPIs) which the literature shows has benefit [ 14 ]. Interestingly, a negative PSMA PET-CT was not a statistically significant predictor of no treatment progression which may indicate the non-visible micro-metastatic disease leading to treatment progression.…”

Activity and safety of KEES - an oral multi-drug chemo-hormonal metronomic combination regimen in metastatic castration-resistant prostate cancer

“…Recently, a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor (olaparib), a new radioactive drug (Lutetium-PSMA) and several new ARTAs demonstrated encouraging outcomes in clinical trials [ 10 – 14 ]. In addition, a substantial amount of research has shown that more intense treatment approaches, rather than castration only, during the early castration sensitive phase improve survival [ 15 ]. Nonetheless, real-world studies have shown that overall survival (OS) in the mCRPC setting remains limited to 31 months in treatment-naïve patients, and only one year in patients progressing on docetaxel [ 16 ].…”

Review of second-generation androgen receptor inhibitor therapies and their role in prostate cancer management

“…Androgen receptor inhibitors have been investigated, refined, and innovated for prostate cancer treatment since the 1960 s [2,3]. The first generation, or 'vintage,' androgen receptor inhibitors include bicalutamide, flutamide, and nilutamide, and had limited efficacy because of their less potent competitive androgen receptor inhibition, explaining their potential to perform as agonists over time, explaining PSA decline upon drug withdrawal [3].…”

“…Multiple mechanisms, including mutations in the androgen receptor gene mutation or amplification, overexpression of androgen receptor co-regulatory molecules, and splice variants, are believed to play a role in the castration resistance state [5]. Second-generation androgen receptor inhibitors competitively inhibit the androgen receptor itself, and thus prevent translocation of the androgen receptor complex inside the nucleus and prevent gene modification and the downstream impact of the androgen receptor complex [2]. Multiple clinical trials are in progress, which will evaluate the role of androgen receptor inhibitors in different clinical settings, in combination with other therapeutics, and in adjuvant or neoadjuvant settings.…”