Natural killer cell activity in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

Abstract

255 Background: Metastatic castration resistant prostate cancer (mCRPC) is the lethal stage for most patients with prostate cancer (PCa). The need for more reliable prognostic and predictive markers for the management of mCRPC is still unmet. The aim of this study was to elucidate the correlation between Natural Killer cell activity (NKA) and treatment outcome in mCRPC patients. Methods: Blood samples were collected prospectively from 87 patients with mCRPC who were treated by enzalutamide as first line treatment. Samples were collected, in NK Vue tubes, at baseline, and prior to each treatment cycle until treatment change. Tubes were placed in an incubator at 37°C within 15 minutes of sampling. Following 20-24 hours of stimulation the level of interferon-gamma (IFNγ) in the plasma was measured, by ELISA (NK Vue) as a surrogate for NKA. Outcomes data were included as endpoints. Results: At the time of biochemical response, plasma IFNγ decreased significantly compared to levels detected at baseline (z-score= 2.334, p=0.019). Additionally, the level of IFNγ was significantly lower at radiological response compared to values at biochemical progression (z-score=2.168, p=0.030). Regarding outcome data, the whole cohort was divided into four groups. In group 1 (n=41) the IFNγ level remained within a normal range (>250 pg/mL), while in group 2 (n=8) it increased from an abnormal (<250 pg/mL) to a normal level. In group 3 (n=13) it dropped to an abnormal level, and it remained at an abnormal level during treatment in group 4 (n=17). There was a significant difference between patients in group 2 and patients in the other three groups regarding both overall survival, radiological free survival and time to next treatment (HR= 3.98, p= 0.012, HR= 6.10, p=< 0.001 and HR= 6.521, p= < 0.001, compared to group 1 respectively). Conclusions: An inverse correlation between NKA and both treatment response and outcome was observed, suggesting a unique role of NK cells in late stage PCa treated with enzalutamide.