Gene signatures may help predict treatment response in patients with prostate cancer

Investigators have uncovered tissue-based transcriptomic signatures that can identify patients with recurrent prostate cancer who are likely to benefit from aggressive systemic therapy concurrent with salvage radiation vs those that may require an alternative approach, according to a retrospective study of data from the phase 2 STREAM trial using the Decipher Genomics Resource for Intelligent Discovery (GRID) database.^1,2

In total, 449 signatures from 31 patients' tissue samples derived from the GRID database underwent genomic analysis.

The prospective, multi-center STREAM study (NCT02057939) assessed the safety and efficacy of enzalutamide (Xtandi) in addition to androgen deprivation therapy (ADT) and salvage radiation in the treatment of patients with prostate cancer. Men included in the study had Gleason 7 to 10 prostate cancer and prostate-specific antigen PSA recurrence to 0.2 0 ng/dL to 4.0 ng/dL within 4 years of radical prostatectomy. Data showed a progression-free survival (PFS) rate of 53% at 3-year follow-up.³

In the most recent retrospective study, the investigators sought to determine which patients may benefit from the treatment combination vs those who may not.

“The STREAM study showed that, despite treatment with 6 months of androgen deprivation therapy and enzalutamide, nearly 50% of patients receiving radiation therapy for prostate cancer that has returned experience relapse within 3 years,” said senior author Andrew Armstrong, MD, ScM, in a news release on the findings.² Armstrong is a professor of medicine and director of research at Duke Cancer Institute Center for Prostate and Urologic Cancers in Durham, North Carolina.

“Using the Decipher GRID database, we found that men in the STREAM study with luminal differentiated genotypes had excellent outcomes, while those whose tumors had a basal, luminal proliferating genotype or other specific genomic characteristics such as PTEN loss had a higher risk of recurrence despite these therapies,” Armstrong added.

In total, 449 signatures from 31 patients' tissue samples derived from the GRID database underwent genomic analysis. Among all patients included in the study, 12.9% had intermediate-risk disease and 87.1% had high-risk disease, according to National Comprehensive Cancer Network risk stratification groups.

Data showed that patients who had luminal differentiated subtype tumors had the longest 3-year PFS at 89%, compared with 19% among patients who had a luminal proliferating tumor subtype (P = .02).

Further, patients who had higher postoperative ADT response signature scores (P = .01) were more likely to have improved PFS with the treatment regimen compared with those who had lower scores.

Conversely, the investigators also found that patients who had signatures for PTEN loss (P = .01) and/or higher homologous recombination deficiency signature scores (P = .009) were more likely to have worse PFS with the treatment regimen than those without PTEN loss or who had lower scores, respectively. These patients, the authors note, may benefit from an alternative therapeutic approach to treatment of enzalutamide with ADT/radiation.

The authors conclude, “These data support the use of transcriptomic signatures in the salvage setting to identify men who may benefit from escalation of systemic therapy concurrent with radiation or from alternative approaches.”

References

1. Bitting RL, Wu Y, Somarelli JA, et al. Transciptomic signatures associated with outcomes in reccurent prostate cancer treated with salvage radiation, androgen-deprivation therapy, and enzalutamide: Correlative analysis of the STREAM trial. JCO Precis Oncol. 2023;7:e2300214. doi:10.1200/PO.23.00214

2. Veracyte announces that findings published in JCO Precision Oncology suggests potential of Decipher GRID-derived gene signatures to predict treatment response in recurrent prostate cancer. News release. Veracyte Inc. August 22, 2023. Accessed August 24, 2023. https://www.businesswire.com/news/home/20230822976286/en/Veracyte-Announces-that-Findings-Published-in-JCO-Precision-Oncology-Suggest-Potential-of-Decipher-GRID-Derived-Gene-Signatures-to-Predict-Treatment-Response-in-Recurrent-Prostate-Cancer

3. Bitting RL, Healy P, George DJ, et al. Phase II trial of enzalutamide and androgen deprivation therapy with salvage radiation in men with high-risk prostate-specific antigen recurrent prostate cancer: The STREAM trial. Eur Urol Oncol. 2021;4(6):948-954. doi:10.1016/j.euo.2020.01.005