A genomic test can now predict which patients with metastatic prostate cancer will benefit from chemotherapy, according to new research published in Cell. The Decipher Prostate Genomic Classifier demonstrated significant predictive ability in identifying patients who respond to docetaxel treatment, potentially transforming treatment decisions for advanced prostate cancer.
STAMPEDE Trial Analysis Validates Predictive Power
The study analyzed data from 1,523 patients enrolled in the multicenter, prospective, phase 3 STAMPEDE trial, with a median follow-up of 14 years. Among the 832 patients with metastatic prostate cancer, those with high Decipher scores experienced a 36% reduction in the risk of death when treated with docetaxel chemotherapy, while patients with lower scores showed less than 4% reduction in death risk.
"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 Professor Gerhardt Attard, director of UCL Cancer Institute and STAMPEDE trial co-investigator. "Treatment intensification with docetaxel, in addition to standard-of-care androgen deprivation therapy, is shown to improve survival for patients with metastatic prostate cancer. However, response rates vary, and clinicians have had limited tools to identify who will likely benefit and who will not."
Significant Survival Benefits for High-Risk Patients
The 22-gene panel, developed using RNA whole-transcriptome analysis, showed statistically significant results in the metastatic population. Patients with high Decipher scores who received docetaxel had a hazard ratio of 0.64 (95% CI, 0.48 to 0.86), compared to 0.96 (95% CI, 0.71 to 1.30) for those with lower scores, with a biomarker-treatment interaction P-value of 0.039.
This finding remained consistent across both low-volume and high-volume metastatic disease subgroups. The test also showed a trend toward improved progression-free survival in high-scoring metastatic patients, though this interaction did not reach statistical significance (P = 0.098).
PTEN Status Enhances Predictive Accuracy
Researchers conducted additional whole-transcriptome analysis that revealed significant biomarker-docetaxel interaction related to PTEN status. In metastatic patients, those with PTEN inactive tumors had a hazard ratio of 0.57 (95% CI, 0.42 to 0.76) compared to 1.05 (95% CI, 0.77 to 1.43) for PTEN active tumors (interaction P = 0.002).
When combining Decipher scoring with PTEN status, patients with metastatic tumors who had both high Decipher scores and PTEN inactive status (230 patients, representing 28% of the metastatic cohort) experienced a 45% reduction in death hazards with docetaxel addition.
"One of our additional discoveries is of a signature that identifies inactivity of the tumor suppressor gene PTEN. This both predicts shorter life expectancy with hormone therapy and greater benefit from chemotherapy, as compared to those with PTEN activity," said Dr. Emily Grist, lead researcher at UCL Cancer Institute.
Limited Benefit in Non-Metastatic Disease
Among the 691 patients with non-metastatic disease, the test showed less discriminatory power. While docetaxel effects were numerically greater in high Decipher tumors (HR 0.75; 95% CI, 0.44 to 1.28) versus lower-scoring tumors (HR 1.04; 95% CI, 0.68 to 1.59), the interaction was not statistically significant (P = 0.302) and was deemed insufficient to clinically justify docetaxel for this population.
Clinical Impact and Availability
The Decipher test has achieved "Level I" evidence status in NCCN Guidelines for prostate cancer and became widely available for US clinicians treating metastatic prostate cancer patients as of June 2025. The test addresses a significant clinical need, as approximately 10,000 men are diagnosed with advanced prostate cancer annually in the UK, and around 55,100 new prostate cancer cases occur yearly.
"By identifying which patients are most likely to have a survival benefit from chemotherapy, we can avoid unnecessary side effects and develop alternative treatments for people with metastatic prostate cancer who are unlikely to benefit," said Professor Gert Attard.
The research represents a collaboration between UCL and Veracyte, with funding support from Prostate Cancer UK, Cancer Research UK, the John Black Charitable Foundation, and the Prostate Cancer Foundation. The STAMPEDE trial continues to be funded by Cancer Research UK and led by researchers at the UCL MRC Clinical Trials Unit and UCL Cancer Institute.
