Abstract
BackgroundCirculating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel.MethodsCTC-counts were assessed in 122 serial samples, as continuous or categorical (<5 vs. ≥5 CTCs) variables, at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD), by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods.ResultsCategorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p = 0.02) and 18.0 (p = 0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p = 0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95 % CI 1.1-13.8, p = 0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95 % CI 0.99-1.05, p = 0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95 % CI 1.6-15.7, p = 0.007) and 1.02 (95 % CI 1.0-1.040, p = 0.04).ConclusionsCategorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1478-4) contains supplementary material, which is available to authorized users.
Highlights
Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer patients
Landmark analyses for circulating tumor cells (CTCs)-counts were performed in a total of 122 samples
Predictive power of categorical and continuous CTC-counts for therapy response We further investigated the predictive power of early categorical CTC-counts (
Summary
Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. In patients with metastatic castration resistant prostate cancer (mCRPC) first-line cytotoxic therapy with docetaxel is standard of care. About 45 % of patients are primary non-responders and tumor progression occurs after a median of 6–8 months [1,2,3,4]. Early prediction of treatment efficacy is relevant for optimized and individualized treatment strategies, especially since recently newer agents like abiraterone, enzalutamide and radium-223 were established which may enable sequential treatment strategies and are applicable either prior or secondary to docetaxel [5,6,7]. The prostatespecific antigen (PSA) value as a tumor marker requires a treatment interval of about 3 months to reach prognostic significance and is unreliable to reveal treatment response, as is the case with other serum derived markers such as lactate dehydrogenase and alkaline phosphatase [5, 9,10,11,12]
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