<p>Metastatic Hormone-sensitive Prostate Cancer: Current Perspective on the Evolving Therapeutic Landscape</p>

Abstract

Introduction: The treatment landscape for patients with metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically in the past five years, despite little change in the preceding 20 years. Such rapid change can make it difficult for clinicians to remain abreast of the current literature and synthesize the relevant data to inform evidencebased treatment decisions. Methodology: We performed a narrative, comprehensive review of treatment options for patients with mHSPC as of December 31, 2019. Specifically, we focused on phase II and III randomized controlled trials assessing the role of chemotherapy, novel androgen axis targeting agents, local-(prostate) directed therapy, and metastasis-directed therapy. Results: The data support a survival benefit with the addition of four different agents to androgen deprivation among men with newly diagnosed prostate cancer-docetaxel, abiraterone acetate, enzalutamide, and apalutamide. While not directly compared, the efficacy of these agents appears similar. That said, there are differences in their toxicity profiles and notable differences in cost between agents. Although analyses encompassing men with lowand high-volume metastases failed to demonstrate a significant survival benefit for radiotherapy treatment to the prostate, new data demonstrates a benefit for men with low-volume metastatic disease. Ongoing trials will assess whether this applies to local surgical treatment. Similarly, metastasis-directed therapy appears beneficial among carefully selected patients. Conclusion: Treatment options for patients with mHSPC are rapidly changing following years of stagnation. A number of systemic therapies offer benefit without significant clinical differences between them. The role for local treatment of the prostate as well as metastatic sites continues to evolve.

Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression

“…The trajectory is characterized by a gradual upregulation of genes related to EZH2 -mediated polycomb signaling and cell cycle progression, most namely G2M checkpoints and mitotic spindle genes. The latter may provide an explanation why taxanes (i.e., docetaxel, cabazitaxel), which disrupt microtubule function during cell division, remain a cornerstone of prostate cancer treatment in the hormone-sensitive and CR metastatic setting 50 – 57 .…”

Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

“…Numerically, all of these interventions improved median overall survival (OS) in a clinically meaningful way compared to ADT alone with hazard ratios (HRs) between 0.61 and 0.88 (14). With the availability of such a broad therapeutic arsenal consisting of agents with different toxicity profiles, clinicians can choose the most suitable treatment option depending on associated comorbidities and burden as well as distribution of disease (15,16).…”

Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression.

“…The latter may provide an explanation why taxanes (i.e. docetaxel, cabazitaxel) which disrupt microtubule function during cell division, remain a cornerstone of prostate cancer treatment in the hormone-sensitive and castration-resistant metastatic setting [49][50][51][52][53][54][55][56] . EZH2 has been previously described to be critically involved in prostate cancer as an activator of AR signaling 30 .…”