True or false: In metastatic prostate cancer, early initiation of a tyrosine‑kinase inhibitor together with androgen deprivation therapy is the standard approach?

False: Tyrosine Kinase Inhibitors Are NOT Standard in Metastatic Prostate Cancer

The statement is FALSE. Androgen deprivation therapy (ADT) alone or combined with androgen receptor pathway inhibitors (ARPIs) or docetaxel chemotherapy—not tyrosine kinase inhibitors—represents the standard approach for metastatic hormone-sensitive prostate cancer.

Standard First-Line Treatment for Metastatic Disease

ADT remains the gold standard systemic treatment for metastatic prostate cancer, achieved through either bilateral orchiectomy or LHRH agonists/antagonists 1. This has been the established standard for decades and continues to be the foundation of treatment 2.

Current Intensification Strategies (Not Tyrosine Kinase Inhibitors)

For patients with metastatic castration-sensitive prostate cancer, the evidence-based intensification options include:

• ADT plus docetaxel chemotherapy: For patients fit enough for chemotherapy, adding docetaxel to ADT at initial diagnosis provides survival benefit 1, 2
• ADT plus ARPIs (abiraterone, enzalutamide, apalutamide): These agents have demonstrated improved radiographic progression-free survival, clinical progression-free survival, and overall survival when combined with ADT 1, 3, 4
• ADT plus abiraterone and prednisolone: Specifically recommended for noncastrate locally advanced nonmetastatic disease based on STAMPEDE trial data, showing significant failure-free survival benefit 1

Why Tyrosine Kinase Inhibitors Are Not Standard

Tyrosine kinase inhibitors are not part of guideline-recommended treatment for metastatic hormone-sensitive prostate cancer 1, 2. While kinase inhibitors are being investigated for castration-resistant prostate cancer (CRPC), they remain experimental and are not established as standard therapy even in that setting 5.

The confusion may arise because:

• Kinase inhibitors are being studied for CRPC, not hormone-sensitive disease 5
• The term "kinase inhibitor" is sometimes incorrectly conflated with androgen receptor signaling inhibitors (ARPIs), which are actually androgen receptor antagonists, not tyrosine kinase inhibitors 6

Evidence-Based Treatment Algorithm

For newly diagnosed metastatic hormone-sensitive prostate cancer:

1. Initiate ADT immediately (continuous castration is preferred over intermittent) 1

2. Add intensification therapy based on patient fitness and disease burden:

   • High-volume disease or fit patients: Consider ADT + docetaxel OR ADT + ARPI (abiraterone, enzalutamide, or apalutamide) 1, 2, 3
   • Low-volume disease: Benefits of intensification are less clear; ADT alone may be appropriate 3
   • Older patients (≥75 years) with high-volume disease: Upfront doublet therapy (ADT + ARSI) shows improved castration-resistant prostate cancer-free survival and overall survival compared to ADT alone 3

3. For resource-constrained settings: Combined androgen blockade using ADT plus first-generation antiandrogen (flutamide, nilutamide, or bicalutamide) may be offered 1

Critical Caveats

• Antiandrogen coverage is mandatory when initiating LHRH agonists in patients with overt metastases to counteract testosterone flare; antiandrogen should precede or be coadministered for at least 7 days 1
• Intermittent ADT is not recommended for metastatic disease outside clinical trials, as it failed to demonstrate non-inferiority to continuous ADT in the SWOG 9346 trial (median OS 5.1 vs 5.8 years) 1
• Real-world data shows suboptimal adoption of ADT intensification, with many patients still receiving ADT monotherapy despite guideline recommendations 4
• Early withdrawal of ARPIs (within 6 months) is associated with poor castration-resistant prostate cancer-free survival and should be avoided through optimal management of adverse events 7

1, 2