ARV7/AR ratio and neutrophil-to-lymphocyte ratio (NLR) as predictors of docetaxel benefit in metastatic castration-resistant prostate cancer patients (mCRPC).

Abstract

254 Background: The constitutively active androgen receptor (AR) variant 7 (ARV7) has been associated to AR inhibitors resistance, but its role in taxane-benefit has not been stablished. Moreover, the neutrophil-to-lymphocyte ratio (NLR) has been associated with poor outcome in prostate cancer.The PBMC population may contain circulating tumor cells (CTCs) but is mainly constituted by lymphocytes and monocytes, that also express the AR. Here we studied the expression of ARV7 and AR in peripheral blood mononuclear cells (PBMC) and its correlation with NLR and clinical outcome in mCRPC treated with docetaxel. Methods: ARV7 and AR mRNAs were tested by quantitative reverse-transcription PCR. Baseline neutrophil and lymphocyte values and PBMC samples were prospectively collected before treatment initiation. Patients were stratified according to NLR ratio (low NLR: ≤3; high NLR:>3) and to ARV7/ARFL ratio expression (Maxstat Cutoff 1.99). Correlation between NLR and PSA progression-free (PSA-PFS) and overall survival (OS), were measured from the start of docetaxel treatment and calculated by log rank test. Results: Fifty patients were included:25 (50%) had low NLR. Thirty-eight patients (76%) expressed high ARV7/ARFL. No significant correlation between NLR with ARV7, AR and ARV7/AR was observed. High ARV7/ARF ratio correlated to a better PSA-PFS (median PSA-PFS 7.47; HR 0.38, 95%CI 0.17-0.85; P=0.0179) , but not OS. High NLR was associated to a lower OS [Median OS was 9.2 months versus 30.17 months in those with low NLR (HR 2.19, 95% CI 1.17-4.09, p= 0.01)]. When both parameters were combined, high NLR and low ARV7/ARFL ratio were associated to a worse PSA-PFS in comparison with low NLR and high ARV7/ARFL ratiogroup(median PSA-PFS: 4.9 vs. 7.5; p=0.008 and HR 5.08, 95% CI 1.33-19.41, p= 0.08) and OS (median OS: 7.4 vs. 30.5; p=0.001 and HR 22.79, 95% CI 4.29-121.17, p= 0.00). Conclusions: The combination of low ARV7/ARFL high NLR and ratio evaluated in PBMC prior to docetaxel treatment has a predictive impact on response and survival in mCRPC patients.