Key Clinical Summary: Emerging Therapies and Multidisciplinary Management in Advanced Prostate Cancer

This is a micro-learning module summary of the Prostate Cancer Education session which you can find here.

Before participating please read our CME and disclosure information which can be found here. This program was supported by an independent medical education grant from Merck. This content is intended for US Healthcare Professionals only.

Introduction: This summary provides an overview of the rapidly evolving landscape for treating advanced prostate cancer, with a focus on integrating new clinical trial data into practice. The discussion emphasizes the central role of the Multidisciplinary Team (MDT) in navigating complex treatment decisions, from initial diagnosis of metastatic disease to later-stage, castration-resistant settings.

The Evolving Standard in Metastatic Castration-Sensitive Prostate Cancer (mCSPC): The Rise of Triple Therapy Recent landmark clinical trials have established a new, intensified standard of care for select patients with newly diagnosed mCSPC.

• Key Trials: The ARASENS (darolutamide) and PEACE-3 (abiraterone) trials demonstrated that adding a novel hormonal agent (NHA) to the existing doublet therapy significantly improves overall survival and progression-free survival.
• Patient Selection: This intensified triplet therapy is most clearly beneficial for patients with high-volume or high-risk disease at diagnosis. The data strongly support its use in this population to achieve better long-term outcomes.
• Clinical Nuance: It is crucial to note that the comparator arm in these trials was ADT plus docetaxel. Triple therapy has not been directly compared to the other standard of care, ADT plus an NHA. Therefore, for patients with lower-volume disease or who are not candidates for chemotherapy, doublet therapy with ADT and an NHA remains a highly effective and appropriate standard.

Precision Medicine in Metastatic Castration-Resistant Prostate Cancer (mCRPC) The treatment of mCRPC is increasingly guided by molecular profiling, moving away from a one-size-fits-all approach.

• PARP Inhibitors:
• Mechanism & Biomarkers: PARP inhibitors (e.g., olaparib, rucaparib, talazoparib) have proven efficacy in patients whose tumours harbour DNA Damage Repair (DDR) gene mutations, most notably BRCA1/2 and ATM. This underscores the necessity of performing genomic testing on tumour tissue or via circulating tumour DNA.
• Combination Therapy: More recently, combination therapy with an NHA and a PARP inhibitor (e.g., abiraterone/olaparib, enzalutamide/talazoparib) has been approved. However, this was studied in NHA-naïve mCRPC patients, and its applicability to patients who have already progressed on an NHA is less clear.
• Key Side Effects: Clinicians should be vigilant for class-specific side effects, particularly cytopenias (especially anemia, which may require transfusions) and significant fatigue.
• Immunotherapy:
• While immunotherapy has limited efficacy in most prostate cancers, pembrolizumab is an option for the small subset of patients with tumours that are Microsatellite Instability-High (MSI-H) or have a high Tumour Mutational Burden (TMB).
• Radioligand Therapy (Theranostics):
• Lutetium-177 PSMA-617: This therapy embodies the "see it, treat it" paradigm. It is indicated for patients with progressive mCRPC who have previously received both an NHA and taxane-based chemotherapy.
• Diagnostic Requirement: Patient eligibility requires a positive PSMA-PET scan to confirm the presence of the target protein on cancer cells.

Optimizing Patient Care Through the Multidisciplinary Team (MDT) Navigating the complexities of advanced prostate cancer requires robust collaboration and clear communication.

• The MDT Framework: The medical oncologist often serves as the "care coordinator," guiding the patient through consultations and treatments with various specialists. This patient-centric model ensures all therapeutic modalities are considered.
• Collaboration with Community Centers: Effective partnerships between tertiary referral centers and community hospitals are vital. Specialized centers can provide expertise on novel therapies and clinical trial access, while local teams can deliver ongoing care, enhancing patient convenience. Clear and frequent communication is the cornerstone of this model.
• Integrating Palliative Care: Given that patients with advanced prostate cancer can live for many years on therapy, early integration of palliative and supportive care is essential. This proactive approach helps manage treatment-related side effects and disease symptoms, improving quality of life, treatment tolerance, and adherence.

Conclusion: The therapeutic arsenal for advanced prostate cancer is expanding rapidly, offering new hope and improved outcomes. The standard of care for newly diagnosed high-volume mCSPC now includes triplet therapy. For mCRPC, treatment is increasingly personalized based on genomic biomarkers (e.g., DDR mutations for PARP inhibitors) and molecular imaging (e.g., PSMA-PET for radioligand therapy). Successfully implementing these advanced strategies hinges on the collaborative expertise of a well-integrated MDT, ensuring that each patient receives a comprehensive and individualized treatment plan from diagnosis through all stages of their disease.