Current Treatment Options for Newly Diagnosed Metastatic Hormone-sensitive Prostate Cancer—A Narrative Review

A Narrative Review

Sean Ong; Jonathan O'Brien; Elizabeth Medhurst; Nathan Lawrentschuk; Declan Murphy; Arun Azad

Disclosures

Transl Androl Urol. 2021;10(10):3918-3930. 

In This Article

Abstract and Introduction

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 hormone-sensitive 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.

Introduction

Prostate cancer incidence has risen all around the world, including in the Asia-Pacific region where it now accounts for more than 120,000 deaths per annum.[1] However, incidence varies with low rates observed in South and East Asia, contrasted with higher rates observed in South East Asia, and among the highest rates in the world reported in Australia.[2] Despite being extremely treatable in its early stages, prostate cancer still remains a leading cause of cancer-related death worldwide,[3] and in Australia, is the second leading cause of male cancer-related deaths.[4] Of these men, approximately one third presented with newly diagnosed or de novo metastatic prostate cancer and two thirds relapsed after prior local therapy.[5] Advanced stage prostate cancer continues to have a poor prognosis which is reflected by a five year survival rate of 31–36%.[6,7]

Androgen deprivation therapy (ADT) has been at the forefront of treatment for metastatic prostate cancer since the Nobel prize winning works of Huggins and Hodges. Unfortunately, although effective at first, all patients inevitably develop a rising PSA or new metastases despite castrate levels of testosterone. This marks the transition to a lethal form of prostate cancer known as castration-resistant prostate cancer (CRPC). The discovery of new androgen receptor pathway inhibitors (ARPIs) and the utility of taxane based chemotherapy in the CRPC setting has resulted in significant gains in overall survival (OS). These agents have more recently been tested for metastatic hormone-sensitive prostate cancer (mHSPC), with all of Docetaxel, Abiraterone, Enzalutamide and Apalutamide yielding significant improvements in OS. This has led to changes in treatment guidelines, approvals and subsidies across the globe.

Given the number of options at our disposal, it is paramount that clinicians have an understanding of new agents, their side effect profile and when to prescribe them. Here we review the current treatment options for mHPSC, discuss decision-making considerations and outline future clinical trials that may alter management of this condition.

We identified the treatment options available for use in mHSPC treatment as well as important clinical aspects including nursing, financial and other decision-making considerations. A search was then performed in PubMed and Google Scholar for the most recent and relevant articles pertaining to the topics identified. An emphasis was placed on phase 3 clinical trials for inclusion into our article. Clinicaltrials.gov was utilised to identify ongoing and future trials for mHSPC. We present the following article in accordance with the Narrative Review reporting checklist (available at http://dx.doi.org/10.21037/tau-20-1118).

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