Alexandra Kienel1, Daniel Porres1, Axel Heidenreich1, David Pfister2. 1. Department of Urology, University Hospital, RWTH Aachen University, Aachen, Germany. 2. Department of Urology, University Hospital, RWTH Aachen University, Aachen, Germany. Electronic address: dpfister@ukaachen.de.
Abstract
PURPOSE: Chemotherapy is an integral part of the treatment of castration resistant prostate cancer. With the introduction of new drugs the need to identify nonresponders is increasing. To our knowledge there are no prognostic parameters to date for use upon the initiation of any treatment. MATERIALS AND METHODS: cfDNA was isolated from a serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier curves. Univariate and multivariate Cox regression analysis was performed to identify independent predictors. RESULTS: Of 59 men 48 (81.4%) had a measurable prostate specific antigen decrease from baseline. Median followup was 15.0 months (range 2.4 to 58.4). The median cfDNA concentration in all men in this study was 27.71 ng/ml (mean 32.64). A threshold of 55.03 ng/ml was significantly associated with a poor prostate specific antigen response of less than 30% (p = 0.005). On univariate and multivariate analysis circulating cfDNA was an independent predictor of overall survival (HR 0.36, 95% CI 0.13-0.97, p = 0.044 and HR 0.34, 95% CI 0.12-0.91, p = 0.032, respectively). Limitations of the study are its retrospective character, and first and second line therapies. CONCLUSIONS: Our trial shows that the cfDNA concentration before therapy may be a useful predictive and prognostic biomarker for prostate specific antigen response and survival.
PURPOSE: Chemotherapy is an integral part of the treatment of castration resistant prostate cancer. With the introduction of new drugs the need to identify nonresponders is increasing. To our knowledge there are no prognostic parameters to date for use upon the initiation of any treatment. MATERIALS AND METHODS: cfDNA was isolated from a serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier curves. Univariate and multivariate Cox regression analysis was performed to identify independent predictors. RESULTS: Of 59 men 48 (81.4%) had a measurable prostate specific antigen decrease from baseline. Median followup was 15.0 months (range 2.4 to 58.4). The median cfDNA concentration in all men in this study was 27.71 ng/ml (mean 32.64). A threshold of 55.03 ng/ml was significantly associated with a poor prostate specific antigen response of less than 30% (p = 0.005). On univariate and multivariate analysis circulating cfDNA was an independent predictor of overall survival (HR 0.36, 95% CI 0.13-0.97, p = 0.044 and HR 0.34, 95% CI 0.12-0.91, p = 0.032, respectively). Limitations of the study are its retrospective character, and first and second line therapies. CONCLUSIONS: Our trial shows that the cfDNA concentration before therapy may be a useful predictive and prognostic biomarker for prostate specific antigen response and survival.
Authors: Esther Campos-Fernández; Letícia S Barcelos; Aline Gomes de Souza; Luiz R Goulart; Vivian Alonso-Goulart Journal: Am J Cancer Res Date: 2019-07-01 Impact factor: 6.166
Authors: Atish D Choudhury; Lillian Werner; Edoardo Francini; Xiao X Wei; Gavin Ha; Samuel S Freeman; Justin Rhoades; Sarah C Reed; Gregory Gydush; Denisse Rotem; Christopher Lo; Mary-Ellen Taplin; Lauren C Harshman; Zhenwei Zhang; Edward P O'Connor; Daniel G Stover; Heather A Parsons; Gad Getz; Matthew Meyerson; J Christopher Love; William C Hahn; Viktor A Adalsteinsson Journal: JCI Insight Date: 2018-11-02