2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Bladder Cancer

Predictive and Prognostic Role of the Neutrophil-To-Lymphocyte Ratio in Muscle Invasive Bladder Cancer Treated with Neoadjuvant Chemotherapy and Radical Cystectomy - Beyond the Abstract

Cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is the guideline-endorsed standard of care for cisplatin-fit patients with clinically non-metastatic muscle-invasive bladder cancer.1 Predicting response to NAC has been a challenging but necessary unmet need in precision medicine. Accurate identification of the patients who are most likely to respond to therapies and thereby avoid unnecessary toxicity-related adverse events is paramount for optimal patient care. However, readily-available, reliable, and validated predictive and prognostic biomarkers to predict response to NAC and survival outcomes in urothelial carcinoma of the bladder (UCB) are still lacking. Systemic inflammatory response biomarkers, such as the blood-based neutrophil-to-lymphocyte ratio (NLR), carry the potential to capture systemic tumor-host interactions to guide treatment planning and clinical decision-making.2 In addition, NLR is cheap and usually available as it is part of normal blood tests.

In this retrospective multicenter study, we assessed the ability of NLR to predict pathological response and survival outcomes after NAC in 404 patients with cT2-4N0-3M0 UCB3. We excluded patients who received adjuvant chemotherapy or radiotherapy as well as patients with an active autoimmune, chronic inflammatory, or hematological disorder.

Based on pretreatment levels of NLR we split the cohort into two groups (high versus low NLR). Next, we fitted several uni- and multivariable (pre- and posttreatment) regression models to assess the discriminatory ability of NLR on the prediction of pathological complete (pT0N0 on final pathology) and partial response (≤pT1), lymph node involvement at RC (ypN+), lymph node response (N-downstaging) at RC, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The predictive accuracy of the models was evaluated using the area under the curve (logistic regression models) and the c-index (Cox regression models). To assess the clinical net benefit of adding NLR to regression models, we used decision curve analysis (DCA).

First, we found that a high pretreatment NLR was associated with adverse pathologic features such as advanced tumor stage, positive soft tissue surgical margins, and lymph node metastases (all p<0.05). Second, we found that a high NLR was associated with a decreased probability of pathological complete or partial response. Moreover, adding NLR to multivariable reference models significantly improved the model’s predictive accuracy for pathological complete (AUC +5.3%, p=0.025) or partial (AUC +4.1%, p=0.04) response but not for lymph node involvement. Similarly, on DCA, adding NLR to a reference model resulted in an increase in the net benefit for pathological complete or partial response, while we found no gain in clinical net benefit of models predicting lymph node involvement.

Regarding survival outcomes, the median follow-up was 49 months (IQR: 25 -70). A high NLR was associated with worse RFS, CSS, and OS on univariable and multivariable (only pretreatment) Cox regression analyses. However, on DCA, we found no gain in clinical net benefit by adding NLR to pre- or postoperative models.

In summary, elevated pretreatment NLR is a promising biomarker for the prediction of response to NAC in UCB. In general, NLR and other systemic inflammatory response biomarkers seem to capture, at least partially, the biological aggressive disease leading to worse survival. Nevertheless, alone they generally fail to improve the clinical net benefit of prediction models. NLR requires further external validation as well as validation in the immunotherapeutic era. Future systemic inflammatory response biomarkers should be assessed in combination to form biomarkers panels with high predictive/prognostic accuracy and determination.

Written by: Markus von Deimling1,2 Victor M. Schuettfort1,2 & Shahrokh F. Shariat1,3-5

  1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  2. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  3. Department of Urology, University of Texas Southwestern, Dallas, Texas, USA
  4. Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, USA
  5. Department of Urology, Second Faculty of Medicine, Charles University, Prag, Czech Republic

References:

  1. Witjes JA, Bruins HM, Cathomas R, et al: European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur. Urol. 2021; 79: 82.
  2. Schuettfort VM, D’Andrea D, Quhal F, et al: A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma. BJU Int. 2022; 129: 182.
  3. von Deimling M, Schuettfort VM, D’Andrea D, et al: Predictive and Prognostic Role of the Neutrophil-to-Lymphocyte Ratio in Muscle Invasive Bladder Cancer Treated With Neoadjuvant Chemotherapy and Radical Cystectomy. Clin. Genitourin. Cancer 2023; in press.
Read the Abstract