Development and Validation of a Prostate Cancer Genomic Signature that Predicts Early ADT Treatment Response Following Radical Prostatectomy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
R Jeffrey KarnesEdward M Schaeffer

Abstract

Purpose: Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.Experimental Design: A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT-treated groups. An ADT Response Signature (ADT-RS) was identified from neuroendocrine and AR signaling-related genes. Two independent cohorts were used to form three separate data sets for validation (set I, n = 232; set II, n = 435; set III, n = 612). The primary endpoint of the analysis was postoperative metastasis.Results: Increases in ADT-RS score were associated with a reduction in risk of metastasis only in a-ADT patients. On multivariable analysis, ADT-RS by ADT treatment interaction term remained associated with metastasis in both validation sets (set I: HR = 0.18, Pinteraction = 0.009; set II: HR = 0.25, Pinteraction = 0.019). In a matched validation set III, patients with Low ADT-RS scores had similar 10-year metastasis rates in the a-A...Continue Reading

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Citations

Jul 12, 2020·Nature Reviews. Urology·Wout Devlies, Frank Claessens
Aug 22, 2018·International Urology and Nephrology·Zhonglin CaiHongjun Li
Aug 8, 2021·Nature Reviews. Urology·Nicholas G ZaorskyAmar U Kishan
Jul 25, 2021·Cancer Research·Asmaa El-KenawiBrian Ruffell
Jul 7, 2021·Prostate Cancer and Prostatic Diseases·Adam B WeinerEdward M Schaeffer

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