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APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial
Xiaolei Shi1, Amol C Shetty2, Jarey Wang3
1Department of Hematology Oncology, University of Maryland Medical Center, Baltimore, MD.
Purpose:
A six-gene panel involved in androgen production, uptake, and conversion (APUC-6: HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, CYP17A1) may define distinct clinical outcomes in metastatic prostate cancer. This study evaluated the prognostic and predictive value of APUC-6 expression in metastatic castration-sensitive prostate cancer (mCSPC).
Methods:
Transcriptomic data from 160 patients in the phase III Eastern Cooperative Oncology Group-ACRIN E3805 CHAARTED trial were analyzed. Patients were stratified into four subgroups based on APUC-6 and androgen receptor (AR) gene expression. Clinical outcomes including time to clinical progression (ttCP), time to castration resistance (ttCR), and overall survival (OS) were assessed within the androgen deprivation therapy (ADT) and docetaxel plus ADT (D-ADT) arms. Interaction testing evaluated the predictive value of APUC-6/AR status. Subgroup analyses were also performed by Decipher genomic risk.
Results:
Patients with APUC-6-high/AR-low expression showed significantly improved ttCP (hazard ratio [HR], 0.43 [95% CI, 0.22 to 0.82]; P = .0092), ttCR (HR, 0.56 [95% CI, 0.32 to 1]; P = .049), and OS (HR, 0.31 [95% CI, 0.16 to 0.61]; P = .0003), but did not appear to benefit from the addition of docetaxel. Conversely, APUC-6-low/AR-low patients demonstrated significantly improved outcomes with D-ADT (ttCP: HR, 0.37 [95% CI, 0.21 to 0.65]; P = .00036; ttCR: HR, 0.38 [95% CI, 0.23 to 0.64]; P = .00017; OS: HR, 0.39 [95% CI, 0.21 to 0.72]; P = .0019). Statistical interaction analysis supported that patients with APUC-6-low/AR-low expression were more likely to benefit from docetaxel (HR, 0.36 [95% CI, 0.19 to 0.66]; P = .001). For patients with a high Decipher genomic classifier score, those in the APUC-6-low subgroup had improved survival with D-ADT, whereas those in the APUC-6-high subgroup did not gain any additional benefit from docetaxel.
Conclusion:
APUC-6 expression and AR gene expression define clinically relevant subgroups in mCSPC and may enhance precision medicine treatment approaches in combination with other transcriptomic biomarkers.
