Integration of circulating tumor cell and neutrophil-lymphocyte ratio to identify high-risk metastatic castration-resistant prostate cancer patients

Weelic Chong,William Kevin Kelly,Grace Lu-Yao,Jianqing Lin,Bingshan Li,Ronald Myers,Chun Wang,Qiang Wei,Hushan Yang,Zhenchao Zhang,Rui Luo,Jian Gu

doi:10.1186/s12885-021-08405-3

Abstract

BackgroundThe neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs.MethodsBaseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models.ResultsCTCs were detected in 37 (58.7%) of 63 mCRPC patients, and among them, 16 (25.4%) had ≥5 CTCs. The presence of CTCs was significantly associated with a 4.02-fold increased risk for progression and a 3.72-fold increased risk of death during a median follow-up of 17.6 months. OS was shorter among patients with high levels of NLR or PLR than those with low levels (log-rank P = 0.023 and 0.077). Neither NLR nor PLR was individually associated with PFS. Among the 37 patients with detectable CTCs, those with a high NLR had significantly shorter OS (log-rank P = 0.024); however, among the 26 patients without CTCs, the OS difference between high- and low-NLR groups was not statistically significant. Compared to the patients with CTCs and low NLR, those with CTCs and high levels of NLR had a 3.79-fold risk of death (P = 0.036). This association remained significant after adjusting for covariates (P = 0.031). Combination analyses of CTC and PLR did not yield significant results.ConclusionAmong patients with detectable CTCs, the use of NLR could further classify patients into different risk groups, suggesting a complementary role for NLR in CTC-based prognostic stratification in mCRPC.

Highlights

Androgen deprivation therapy (ADT) is a commonlyused first-line treatment for men with advanced prostate cancer
We reviewed data from our prospective metastatic CRPC (mCRPC) cohort, analyzed baseline circulating tumor cells (CTCs) together with neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), two hematological prognostic factors, and evaluated their joint impact on mCRPC survival
Patient characteristics Sixty-three mCRPC patients with both CTC enumeration results and NLR/PLR values were included in this analysis

Summary

Introduction

Androgen deprivation therapy (ADT) is a commonlyused first-line treatment for men with advanced prostate cancer. Receiving ADT, the vast majority of patients eventually progress to a disease state known as castration-resistant prostate cancer (CRPC) [1]. A variety of markers, including circulating tumor cells (CTCs) and gene expression profiles, are being studied to identify subsets of metastatic CRPC (mCRPC) patients who have significantly different prognoses [2, 3]. CTCs have been associated with a poor prognosis in mCRPC patients [3, 4]. A pooled analysis of five randomized clinical trials demonstrated CTC count to be a response measure in these patients [5]. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). No study has examined the prognostic value of NLR and PLR in the context of CTCs

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