Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study

Abstract

Background There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. Patients and methods CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m 2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan–Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. Results The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). Conclusions High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.

Change of the Neutrophil-to-Lymphocyte Ratio during Treatment: A Potential Prognostic Biomarker in Metastatic Prostate Cancer Treated with Radium-223 Dichloride

“…In the docetaxel-treated group, we found that the NLR at baseline and at 12 weeks was not associated with OS. Even if our findings are consistent with Sumbul et al and Linton et al [ 19 , 20 ], many other studies have shown, for different NLR cut-offs, that the NLR ratio was associated with longer OS in chemotherapy-treated patients [ 3 , 18 , 21 , 22 , 23 ]. This difference in our patients could be explained by a lack of statistical power and the fact that prostate cancer is considered an immunologically cold cancer [ 24 ].…”

“…Despite, the therapeutic progress made recently, life expectancy remains poor. A better understanding of the predicting treatment response is needed to optimize the use and the sequencing of available therapies [ 3 ]. Lymphocytes and neutrophils have been implicated in host immune response to cancer including prostate cancer, either as a factor of host defense or tolerance [ 4 ].…”

New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors

“…In the resulting Cox proportional hazards models, all factors previously identified by the Bellmunt model, that is, ECOG PS, hemoglobin and liver metastases, were independent predictors of survival. TFLC, previously identified as an important prognostic factor, 12 ALP, bone metastases and NLR were also retained in both models. Tumor–node–metastases stage at diagnosis was not retained in the model without PD-L1 expression.…”

Prognostic value of neutrophil‐to‐lymphocyte ratio in patients with metastatic castration‐resistant prostate cancer receiving prostate‐specific membrane antigen targeted radionuclide therapy

“…In addition, the cut-off defining low versus high NLR differs from previous publications and might be considered arbitrary. 15,24,[46][47][48] However, there is no clear consensus regarding the optimal cut-off. There are numerous studies and meta-analyses conducted in prostate cancer investigating the prognostic value of NLR across the whole spectrum of the disease.…”