Genomic Test Predicts Chemotherapy Benefit in Metastatic Prostate Cancer

Data from the randomized, prospective, phase 3 STAMPEDE trial (NCT00268476) show that the Decipher Prostate Genomic Classifier can predict which patients with metastatic prostate cancer are likely to benefit from treatment intensification with the chemotherapy docetaxel and which are not.^1,2

The findings, published in Cell, represent the first time a gene expression test has been demonstrated to help clinicians personalize chemotherapy decisions for this patient population, addressing a significant unmet need.

Treatment intensification with docetaxel in addition to standard-of-care androgen deprivation therapy (ADT) is a key strategy for managing metastatic prostate cancer. While it is known to improve survival, clinical response rates can vary, and until now, clinicians have had limited tools to prospectively identify which patients will derive the most benefit. The results from the STAMPEDE trial suggest that this genomic classifier may provide a new tool to guide these critical treatment decisions, potentially sparing patients from unnecessary toxicity and side effects.

"Our findings suggest that the Decipher Prostate test may provide an important new tool to help guide treatment decisions for the growing population of patients with metastatic prostate cancer," said Gerhardt Attard, MD, director of University College London Cancer Institute and STAMPEDE trial co-investigator, in a press statement.¹ "Our results demonstrate the Decipher test’s ability to make this distinction."

The study, which involved 1523 patients with high-risk or metastatic prostate cancer, focused on 832 patients with metastatic disease who were followed for a median of 14 years. Patients were randomized to receive either ADT alone or ADT plus docetaxel. Analysis revealed a significant interaction between the Decipher score and treatment benefit.

Among patients with higher Decipher scores, the addition of docetaxel conferred a clear survival benefit (HR, 0.64; 95% CI, 0.48–0.86), while patients with lower scores did not experience a statistically significant benefit from the chemotherapy (HR, 0.96; 95% CI, 0.71–1.30; P =.039). This finding is particularly noteworthy as the predictive ability of the test remained consistent regardless of each patient’s metastatic disease volume. This contradicts the prevailing clinical practice, which often favors docetaxel use primarily in patients with high-volume metastatic disease. The genomic classifier provides a more nuanced, biology-driven approach to patient selection, moving beyond purely clinical and anatomic factors.

The expanded-use version of the test for metastatic disease became available to clinicians in the United States in June 2025, developed as part of an ongoing collaboration between Veracyte and University College London. The study also explored other gene signatures, with one notable finding being that metastatic tumors with both a high Decipher score and a PTEN-inactive gene signature showed the greatest benefit from the addition of docetaxel. This suggests future opportunities for even more personalized therapeutic strategies.

Prostate cancer remains a substantial global health burden. An estimated 1.5 million new cases are diagnosed annually, and the disease accounts for nearly 400,000 deaths in patients worldwide. In the United States, approximately 315,000 new cases are expected this year, making it the second-leading cause of cancer death among American men. Most prostate cancer deaths occur in patients with advanced or metastatic disease, a group that has been growing in recent years.

The integration of advanced genomic classifiers like the Decipher test into clinical practice represents a significant step forward in the era of precision oncology. By providing clinicians with actionable, evidence-based insights into a tumor's biological profile, these tools empower more informed treatment decisions, aiming to maximize therapeutic benefit while minimizing unnecessary toxicities for patients facing a serious and increasingly common diagnosis.

This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. Veracyte Announces New Study Published in Cell Shows that Decipher Prostate Test Predicts Chemotherapy Benefit in Patients with Metastatic Prostate Cancer. News release. Veracyte Inc. August 28, 2025. Accessed August 28, 2025. https://tinyurl.com/yru6j238

2. Grist E, Dutey-Magni P, Parry MA, et al. Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers. Cell. 2025. doi:10.1016/j.cell.2025.07.042