Zachery Roger Reichert, MD, PhD, discusses key research questions to explore in early-stage prostate cancer.
The treatment landscape in prostate cancer continues to improve with the continued development of novel drug classes and therapeutics, such as oral androgen signaling receptor inhibitors and darolutamide (Nubequa) in combination with docetaxel, Reichert begins. Despite this wealth of options, uncertainty remains regarding how to identify the optimal candidates for a given approach, Reichert says.
To address this knowledge gap, research in early-stage metastatic hormone-sensitive prostate cancer is focused on the predictive value of clinical features such as disease distribution, Reichert states, as well as biomarkers like circulating tumor DNA, circulating tumor cells, and the RNA sequence. Many patients in clinic do not experience responses with intensified doublet and triplet regimens despite their efficacy in a clinical trial setting, he notes. As such, it is vital to pinpoint patients with high-risk features early in the treatment course, Reichert says. This allows patients to gain a more accurate understanding of their disease prognosis, receive the most beneficial standard regimen, and potentially be directed towards clinical trials targeting difficult-to-treat pathways, Reichert explains.
In addition, clinical trials in prostate cancer may also be designed to address questions regarding lineage plasticity. This includes how to exploit key pathways and proteins involved in this clinical phenomenon, how to determine when patients' disease transitions to a more aggressive variant, and whether to focus on them prior to or following this shift, Reichert details. Another intriguing research topic is the viability of utilizing bipolar testosterone to undo the epigenetic reprogramming responsible for lineage plasticity, he adds. Individual institutions will have to determine which questions to focus on, although all are important and promising avenues for future collaboration, Reichert concludes.