Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8–90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7–4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5–9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5–14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2–20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07–1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10–1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients

Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ?3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8-90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7-4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5-9.7) in those with NLR ?3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5-14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2-20.9) in those with baseline NLR ?3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07-1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10-1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients

Association between early PSA increase and clinical outcome in patients treated with enzalutamide for metastatic castration resistant prostate cancer

Objective Prostate-specific antigen (PSA) decline by 50 % from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the association between PSA changes at 4 weeks and clinical outcome. Patients and Methods Eligible patients had PSA levels assessed at baseline, and monthly during enzalutamide treatment. Early PSA increase was defined as an increased PSA level at 4 weeks ≥20 % (PSA + 20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥30 % (PSA30w4) and ≥50 % (PSA50w4) from baseline. Progression-free survival (PFS), overall survival (OS) and their 95 % confidence intervals (CI) were evaluated by the Kaplan–Meier method and compared with the log-rank test. The impact of early PSA increase and decline on PFS and OS was evaluated by Cox regression analyses. Results We assessed 193 patients with median age of 73 years (range 43–91 years). The median follow-up was 11.7 months (range 0.5–27.4 months). PSA + 20w4 predicted both PFS and OS [HR 6.50 (95 % CI 2.63–16.07; p < 0.0001) and HR 10.54 (95 % CI 4.02–27.64; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95 % CI 0.21–0.67; p = 0.0009) and HR 0.34 (95 % CI 0.19–0.60; p = 0.0003), respectively]. Conclusions An early PSA increase, defined as a PSA level at 4 weeks ≥20 % (PSA + 20w4), could be useful to quickly identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA + 20W4 as an early biomarker of primary resistance to enzalutamide

Change in NLR and survival.

<p>Change in NLR and survival.</p

Overall survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.

<p>Overall survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.</p

Changes in NLR and PSA response rate at 12weeks.

<p>Changes in NLR and PSA response rate at 12weeks.</p

Forest plot for progression-free survival.

<p>Forest plot for progression-free survival.</p

Progression-free survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.

<p>Progression-free survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.</p

Forest plot for overall survival.

<p>Forest plot for overall survival.</p