Cell-free DNA as a surrogate marker in patients with CRPCA undergoing taxane-based chemotherapy.

Abstract

e584 Background: Taxane-based chemotherapy is one of the first-line life prolonging therapeutic approaches in metastatic castration-resistant prostate cancer (mCRPCA). Until now, there is no valid surrogate marker directly reflecting therapeutic response. Prostate specific antigen (PSA) and imaging studies are used to monitor therapy. The aim of this study was to assess whether circulating cell-free DNA (cfDNA) is suitable as a predictive and prognostic marker. Methods: cfDNA was isolated in 74 patients with mCRPCA receiving taxane based chemotherapy. Median serum cfDNA - concentration was correlated with localization of metastasis and tumor burden (bone, lymph node and visceral). In addition we examined the change of cfDNA - concentration under treatment. The median serum cfDNA - concentration at the time of 1st, 5th and 10th cycle of chemotherapy was correlated with PSA response (>80%, >50%, <30% decrease). Results: We identified 21 patients with a PSA decrease >80%, 41 patients with a PSA decrease >50%, 12 patients with a PSA decrease <30 % and 15 patients with a PSA rise during treatment. Median cfDNA concentration in patients with a PSA decrease of >80% was 34.96 ng/ml, in patients with a PSA decrease > 50% 34.96 ng/ml and in patients with a PSA decrease < 30% 38.475 ng/ml. The Median cfDNA concentration in patients with a PSA rise was 31.25 ng/ml. Median cfDNA concentration in patients with lymph node metastasis was 33.78 ng/ml, with bone metastasis < 3 34.24 ng/ml, bone metastasis >3 31.97 ng/ml and with visceral metastasis 34.57 ng/ml. There was no significant correlation between median cfDNA - concentration and type of metastasis (cfDNA vs. PSA bone metastasis <3, P = 0,56938, cfDNA vs. PSA bone metastasis >3 P = 0.472, cfDNA vs. PSA lymph node metastasis P = 0.423). There was no significant change of median cfDNA concentration under treatment ( P > 0.05). Conclusions: Although cfDNA-concentration is a prognostic and predictive marker for survival and therapy response as shown recently, our findings suggest that cfDNA as a surrogate marker is unsuitable.