Therapy Optimization in mHSPC: Insights from a Multidisciplinary Uro-Oncology Expert Panel

Metastatic hormone-sensitive prostate cancer (mHSPC) is a disease state characterized by the presence of distant metastases detectable on conventional imaging while the tumor remains responsive to androgen deprivation therapy (ADT). It represents an earlier, treatment-sensitive phase that precedes the development of metastatic castration-resistant prostate cancer (mCRPC), the terminal stage of the disease. The addition of therapies beyond traditional ADT to achieve more sustained tumor regression by combining different mechanisms of action and targeting different cancer fuelling pathways has spurred the concept of treatment intensification in prostate cancer. This approach may involve the addition of androgen receptor pathway inhibitors (ARPIs) to ADT-hereafter referred to as "treatment intensification"-or the addition of ARPIs plus chemotherapy to ADT-hereafter referred to as "treatment optimization." Randomized controlled trials have consistently shown improved patient outcomes with the evolution from ADT alone to ADT plus ARPI, and more recently to ADT plus ARPI plus docetaxel, and demonstrated that treatment intensification decisions in mHSPC have clinically meaningful implications. However, in the absence of comparative efficacy data between therapy options, the treatment choice for a given patient will depend on patient- and disease-related factors, with the goal of improving outcomes while minimizing the cumulative toxicity of therapies, particularly when using combination strategies. In this article, a panel of 28 experts-8 urologists and 20 oncologists-with recognized experience and expertise in the management of advanced prostate cancer discussed the role of treatment intensification in mHSPC and which patients are more likely to benefit from each treatment strategy.