Genomic Test Predicts Chemotherapy Benefit in Metastatic Prostate Cancer

In the United States, about 334,000 men are diagnosed with prostate cancer each year, with roughly 30,000 presenting with metastatic disease. Clinicians need objective tools to determine who benefits from treatment intensification and who can safely avoid it. 

Veracyte’s (South San Francisco, CA, USA) Decipher Prostate test was evaluated in the international, randomized Phase III ENZAMET trial presented at the 2026 ASCO Annual Meeting. The analysis provides the first Level 1B evidence that a genomic assay can guide decisions on triplet therapy—chemotherapy added to standard hormonal therapy with androgen-deprivation therapy (ADT) plus enzalutamide—in metastatic disease. Findings also build on prior validations from the STAMPEDE and CHAARTED trials, extending predictive utility from ADT alone to doublet therapy with an androgen receptor pathway inhibitor (ARPI).

The Decipher Prostate test is a transcriptomic genomic classifier that generates a score used as a predictive biomarker. In ENZAMET, investigators conducted a prespecified biomarker analysis in 634 patients, with a median follow-up of 5.6 years, to assess whether Decipher could predict benefit from adding docetaxel to ADT plus enzalutamide. Patients with higher Decipher scores (>0.85) and high-volume disease derived clinically meaningful survival improvement with triplet therapy compared with standard hormonal therapy, while those with lower scores showed no benefit from chemotherapy, indicating it may be safely avoided. The treatment-by-biomarker interaction was statistically significant (p=0.043), supporting the test’s predictive value. Notably, men with higher Decipher scores who received triplet therapy had more aggressive features but achieved survival comparable to lower-risk patients on doublet therapy.

Complementary data presented at ASCO from a combined analysis of four mature NRG/RTOG trials in high-risk localized prostate cancer further reinforce clinical utility. Decipher Prostate significantly improved prognostic accuracy for survival outcomes compared with clinical variables alone and reclassified approximately one in four patients when integrated with National Comprehensive Cancer Network risk categories. The results also indicate that many more clinically high-risk patients may benefit from treatment intensification with an ARPI.

“For the first time, the ENZAMET trial analysis shows that a genomic test can guide the decision to add chemotherapy to standard of care hormonal therapy in metastatic prostate cancer,” said Prof. Christopher Sweeney, M.B.B.S., DHS., Lead Investigator, South Australian Immunogenomics Cancer Institute, Adelaide University. “Decipher Prostate identifies which patients benefit from treatment intensification, and which can be safely spared chemotherapy, giving clinicians an actionable, evidence-based answer.”

“Decipher Prostate is the most validated transcriptomic test across the full prostate cancer continuum – from active surveillance through metastatic disease,” said Elai Davicioni, Ph.D., Veracyte’s Medical Director, Urology. “For clinicians, that means a clearer answer at every decision point. For patients, it means greater confidence that their treatment is guided by the biology of their disease, and not guesswork.”

Related Links
Veracyte