ASCO GU 2025: New Study Tries to Identify Key Factors That Influence How Quickly Prostate Cancer Becomes Resistant to Hormone Therapy

Androgen deprivation therapy (ADT) is the foundation of treatment for advanced prostate cancer, but many patients eventually develop castration-resistant prostate cancer (CRPC)—a stage where the cancer stops responding to hormone therapy. A new real-world study, analyzing over 41,000 patients treated between 1991 and 2020, has identified several key factors that influence how quickly this resistance develops.

The study compared two common types of ADT:

  • LHRH agonists (e.g., triptorelin, leuprolide, goserelin) initially cause a temporary testosterone surge before suppressing production over time.
  • GnRH antagonists (e.g., degarelix, relugolix) directly block testosterone production without an initial surge and may achieve faster suppression.

Patients treated with GnRH antagonists progressed to CRPC faster than those on LHRH agonists. The median time to CRPC was 10.9 months for antagonists vs. 17.3 months for agonists. After adjusting for other factors, antagonist use was associated with a 40% higher risk of faster CRPC onset (HR 1.40, p=0.02).

Other Findings

Patients with metastases beyond the prostate (e.g., in bones or organs) developed CRPC significantly faster than those without metastases.

Patients treated in oncology centers developed CRPC much faster than those managed in urology clinics. This may reflect more aggressive disease in patients treated by oncologists, as urologists typically manage earlier-stage cases.

Patients without diabetes had a 45% higher risk of developing CRPC sooner than those with diabetes

Similarly, patients who were not taking statins had a 43% higher risk of faster CRPC onset than those on statins.

So, in a nutshell:

LHRH agonists may be preferable to GnRH antagonists for delaying CRPC in certain patients.
Patients with metastatic disease require closer monitoring, as they are at higher risk of early CRPC.
The potential protective effects of diabetes and statins warrant further investigation—some diabetes medications and statins may have indirect anti-cancer properties.

Source.