Decipher test is predictive of chemotherapy benefit in metastatic prostate cancer

Data published in Cell indicate that the Decipher Prostate Genomic Classifier can predict which patients with metastatic prostate cancer will benefit from treatment intensification with the chemotherapy docetaxel.¹

The Decipher test—a 22-gene panel developed using RNA whole-transcriptome analysis—was applied to prostate cancer samples obtained from the multicenter, prospective, phase 3 STAMPEDE trial (NCT00268476).

“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, MD, PhD, director of UCL Cancer Institute and STAMPEDE trial co-investigator, in a news release on the findings.² “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. Our results demonstrate the Decipher test’s ability to make this distinction.”

In total, the study collected data from 1523 patients with metastatic (n = 832) or non-metastatic (n = 691) prostate cancer. Patients were all enrolled in the STAMPEDE trial, where they were randomly assigned to receive standard of care treatment with androgen deprivation therapy (ADT) or to ADT plus docetaxel or abiraterone acetate (Zytiga). The median follow-up was 14 years.

Decipher and Docetaxel

In patients with metastatic prostate cancer (n = 832) the addition of docetaxel clinically and statistically significantly improved survival in those with a high Decipher score (HR, 0.64; 95% CI, 0.48 to 0.86), but not among patients with a lower Decipher score (HR, 0.96; 95% CI, 0.71 to 1.30; biomarker-treatment interaction P = .039)

This finding was consistent across low-volume and high-volume metastatic disease subgroups.

There was also a trend toward improved progression-free survival in patients with metastatic disease who had high Decipher scores, but this interaction did not reach statistical significance (biomarker-treatment interaction P = .098).

In patients with non-metastatic disease, the authors reported, “although the effect of docetaxel was numerically greater in high Decipher tumors (high, HR, 0.75; 95% CI, 0.44 to 1.28; lower, HR, 1.04; 95% CI, 0.68 to 1.59), this was neither large enough for an interaction effect (biomarker-treatment interaction P = .302) nor to clinically-justify docetaxel for this population.”

Decipher and Abiraterone

The investigators also assessed the Decipher test’s ability to predict abiraterone benefit. In patients with metastatic disease, the addition of abiraterone showed greater benefit in patients with higher Decipher scores (HR, 0.44; 95% CI, 0.32 to 0.62) vs lower Decipher core (HR, 0.70; 95% CI, 0.49 to 1.00). However, this finding was “neither statistically significant (P = .061) nor clinically relevant, given both subgroups had meaningful benefit,” according to the authors.

Biomarker-Docetaxel Interaction

The investigators also performed whole-transcriptome analysis of prostate samples, finding significant biomarker-docetaxel interaction. In patients with metastatic disease, the HR for PTEN inactive was 0.57 (95% CI, 0.42 to 0.76) vs 1.05 (95% CI, 0.77 to 1.43) for PTEN active (interaction P = .002).

When combining this finding with the predictive utility of Decipher, the investigators found that patients with metastatic tumors who had a high Decipher score and PTEN inactive tumors (n = 230; 28% of metastatic tumor) had 45% reduction in the hazards of death with the addition of docetaxel.

As of June 2025, the Decipher test has been made widely available for clinicians in the US who are treating patients with metastatic prostate cancer.

“The Decipher Prostate test’s ability to help guide treatment for patients with localized prostate cancer has already been established in dozens of peer-reviewed publications and it is the only gene expression test to achieve ‘Level I’ evidence status in the most recent NCCN Guidelines for prostate cancer,” said Elai Davicioni, PhD, Veracyte’s medical director for urology. “This new publication provides important clinical evidence from a phase 3 trial that supports expanded use of our test to patients with metastatic cancer—an area where there is a clear unmet need.”

REFERENCES

1. 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

2. Veracyte announces new study published in Cell shows that Decipher Prostate Test predicts chemotherapy benefit in patients with metastatic prostate cancer. News release. Veracyte. August 27, 2025. Accessed August 27, 2025. https://investor.veracyte.com/news-releases/news-release-details/veracyte-announces-new-study-published-cell-shows-decipher