The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) has undergone a significant transformation, with combination therapy approaches now replacing androgen deprivation therapy (ADT) monotherapy as the standard of care.
According to the latest 2025 guidelines, ADT with intensification is now the recommended approach for patients with mHSPC. This shift represents a major advancement in the management of this challenging disease state.
Multiple Intensification Options Available
Clinicians now have several evidence-based intensification options to consider when treating patients with mHSPC. These include:
- Abiraterone acetate (with prednisone)
- Darolutamide
- Docetaxel chemotherapy
Each of these agents has demonstrated significant clinical benefits when added to ADT in large-scale clinical trials.
Key Clinical Trials Supporting Combination Approaches
Several pivotal clinical trials have established the superiority of combination approaches over ADT alone:
ARANOTE Trial
The ARANOTE trial evaluated the efficacy of darolutamide in combination with ADT. Results demonstrated significant improvements in both overall survival and delayed disease progression compared to ADT monotherapy.
ARASENS Trial
This landmark study further validated the role of darolutamide in the mHSPC setting, showing substantial survival benefits when added to standard therapy.
TITAN Trial
The TITAN trial investigated the addition of apalutamide to ADT, revealing meaningful improvements in survival outcomes and time to disease progression.
Dr. Jack Andrews, a urologic oncologist involved in these studies, noted, "The evolution to combination therapy approaches represents a significant paradigm shift in the management of mHSPC, with multiple effective options now available."
Personalized Treatment Selection
With multiple intensification options now available, treatment selection can be tailored based on individual patient characteristics, comorbidities, and preferences. Factors that may influence treatment decisions include:
- Patient age and performance status
- Comorbid conditions
- Disease volume and distribution
- Prior treatments
- Quality of life considerations
"When selecting therapy, we now consider not only efficacy but also side effect profiles and how they might impact a patient's quality of life," explained Dr. Eugene Cone, who specializes in advanced prostate cancer management.
Quality of Life Considerations
As treatment options expand, quality of life has become an increasingly important consideration in treatment selection. Different intensification approaches carry varying side effect profiles that may impact patients differently.
Dr. Arash Rezazadeh emphasized, "While survival benefit remains our primary goal, we must balance this with maintaining the best possible quality of life for our patients. The good news is that we now have multiple effective options that allow us to personalize treatment approaches."
Future Directions
The treatment landscape for mHSPC continues to evolve rapidly. Ongoing research is exploring novel therapeutic approaches, including:
- New hormonal agents
- Immunotherapies
- PARP inhibitors
- Combination strategies with three or more agents
These emerging approaches may further reshape care pathways for patients with mHSPC in the coming years.
Clinical Implications
The shift away from ADT monotherapy represents a significant advancement in the management of mHSPC. Key takeaways for clinicians include:
- ADT monotherapy is no longer considered the standard of care for most patients with mHSPC
- Multiple evidence-based intensification options exist
- All intensification approaches demonstrate benefit over ADT alone
- Treatment selection should be individualized based on patient and disease characteristics
As the treatment landscape continues to evolve, ongoing education and familiarity with emerging data will be essential for clinicians managing patients with mHSPC.
