Role of Serum Lymphocyte-derived Biomarkers in Nonmetastatic Muscle-invasive Bladder Cancer Patients Treated with Trimodal Therapy

Abstract

Background: The role of serum lymphocyte-based biomarkers, such as the neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios, was previously studied in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy but remains underexplored in patients treated with trimodal therapy (TMT).

Objective: To analyze the impact of serum lymphocyte-based biomarkers on main oncological outcomes after TMT for MIBC.

Design setting and participants: A retrospective study, including 176 patients treated with TMT for nonmetastatic MIBC (cT2-4/cN0-2) between 2001 and 2017 at a tertiary academic center, was conducted.

Intervention: TMT, consisting of initial maximal transurethral resection of the bladder tumor, followed by radiotherapy with concurrent chemotherapy.

Outcome measurements and statistical analysis: Clinicopathological characteristics, serum laboratory tests, and imaging reports were collected. NLR, LMR, and PLR were calculated before and at the end of TMT. Dynamic patterns of NLR, LMR, and PLR during TMT were studied. Multivariable regression models were performed to estimate the effect of these biomarkers on complete response (CR) to TMT and survival.

Results and limitations: The median age was 75 yr (interquartile range 66-82). Staging was cT2 in 156 (89%) and cN0 in 159 (90%) patients. A pretreatment NLR (pre-NLR) of ≥4.0 was independently associated with lower CR rates (odds ratio 0.32; p = 0.013). In addition, a pre-NLR of ≥4.0 was associated with worse cancer-specific survival (hazard ratio [HR] 1.88; p = 0.032) and overall survival (OS; HR 1.61; p = 0.033) together with other factors such as hydronephrosis, Eastern Cooperative Oncology Group performance status, and cT stage 3-4a. When both pre- and post-treatment variables were considered, an increase in NLR beyond 75% during TMT (HR 1.63; p = 0.035) was associated with worse OS. This study was limited by its retrospective design.

Conclusions: A high pre-NLR value was independently associated with lower rates of CR and worse survival in MIBC patients undergoing TMT. Prospective validation is needed to implement NLR into clinical practice.

Patient summary: In this study, we reported the oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal therapy. We found that the neutrophil-to-lymphocyte ratio, a cheap and available blood-derived biomarker, was associated with response to trimodal therapy and survival outcomes.

Keywords: Biomarkers; Bladder cancer; Prognosis; Radiotherapy.

Fig. 1

(A and B) Cancer-specific and overall survival Kaplan-Meier plots for all patients and (C and D) stratified by pre-NLR status. CSS = cancer-specific survival; NLR = neutrophil-to-lymphocyte ratio; OS = overall survival.