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 withmetastasis 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-yearmetastasis rates in the a-ADT and no-ADTgroups (30.1%vs. 31.0%, P = 0.989).AmongHigh ADT-RS patients, 10-year metastasis rates were significantly lower for a-ADT versus no-ADT patients (9.4% vs. 29.2%, P = 0.021). The marginal ADT-RS by ADT interaction remained significant in the matched dataset (Pinteraction = 0.035).
Conclusions: Patients with High ADT-RS benefited from a-ADT. In combination with prognostic risk factors, use of ADT-RS may thus allow for identification of ADT-responsive tumors that may benefit most from early androgen blockade after radical prostatectomy. We discovered a gene signature that when present in primary prostate tumors may be useful to predict patients who may respond to early ADT after surgery.
Karnes, R. Jeffrey; Sharma, Vidit; Choeurng, Voleak; Ashab, Hussam Al-Deen; Erho, Nicholas; Alshalalfa, Mohammed; Trock, Bruce; Ross, Ashley; Yousefi, Kasra; Tsai, Harrison; Zhao, Shuang G.; Tosoian, Jeffrey J.; Haddad, Zaid; Takhar, Mandeep; Chang, S. Laura; Spratt, Daniel E.; Abdollah, Firas; Jenkins, Robert B.; Klein, Eric A.; Nguyen, Paul L.; Dicker, Adam P.; Den, Robert B.; Davicioni, Elai; Feng, Felix Y.; Lotan, Tamara L.; and Schaeffer, Edward M., "Development and Validation of a Prostate Cancer Genomic Signature that Predicts Early ADT Treatment Response Following Radical Prostatectomy." (2018). Department of Radiation Oncology Faculty Papers. Paper 122.