Overview
Prostate cancer varies widely in aggressiveness. Patients initially diagnosed with non-metastatic high-risk or very high-risk disease (based on PSA levels, tumor grade, and stage) are at increased risk for recurrence and death despite surgery or radiation therapy. New drugs called androgen receptor pathway inhibitors (ARPIs) have shown promise in this setting, but real-world adoption and outcomes remain poorly understood.
Researchers used Flatiron Health’s US Prostate Cancer Panoramic Database, inclusive of more than 380,000 patients with prostate cancer, to analyze data from over 63,000 patients with high-risk and very high-risk non-metastatic prostate cancer diagnosed between 2011-2025. While surgery was more common in the high-risk group (42% vs. 28%) and radiation therapy was more common in the very high-risk group (78% vs. 68%), ARPI use was low across both groups. Only 2.6% of patients received an ARPI within 6 months of primary treatment, and use was only marginally higher (6.2%) in the very high-risk group compared with the high-risk group (2.2%). However, after biochemical recurrence occurred, 52% of patients received an ARPI before distant metastasis (64% in the very high-risk group and 50% in the high-risk group). Patients with very high-risk disease experienced worse outcomes: more biochemical recurrence, shorter time to metastasis, and shorter overall survival compared to high-risk patients.
Why this matters
These findings reveal substantial underutilization of ARPIs in the localized prostate cancer setting, despite their potential benefit. As additional ARPIs become approved for early prostate cancer, understanding real-world outcomes and barriers to access becomes critical. The study highlights an opportunity to improve outcomes for high-risk patients through earlier ARPI use, while emphasizing the need for future research comparing real-world outcomes of patients receiving early versus delayed ARPI therapy.