The Prognostic Role of the Change in Neutrophil-to-Lymphocyte Ratio During Neoadjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer: A Retrospective, Multi-Institutional Study

Abstract

Background:The impact of the change in the neutrophil-to-lymphocyte ratio (NLR) during neoadjuvant chemotherapy (NAC) on outcomes in patients with muscle-invasive bladder cancer (MIBC) is poorly understood.Objective:To evaluate the prognostic impact of the change in NLR during NAC for patients with MIBC.Methods:Patients referred to academic, community, and quaternary referral centres in Alberta, Canada from 2005 to 2015, Ontario, Canada from 2005 to 2013, and Southampton, UK from 2004 to 2010 were evaluated. 376 eligible patients were treated with NAC for clinical T2-4aN0M0 disease, and 296 were evaluable for the change in NLR. A high NLR was defined as being an NLR > 3. Relationships between the change in NLR from baseline to mid-NAC (pre-cycle 3) and outcomes were analyzed using multivariable Cox regression. Kaplan-Meier analysis was used with the log-rank test for group comparisons.Results:Median follow-up was 22.0 months (95% confidence interval [CI]: 14.9–30.0). Patients with a sustained high NLR had a median disease-free survival (DFS) of 12.6 months, compared to 34.8 months for those with a sustained low NLR (log-rank test p = 0.0025; hazard ratio [HR] 0.61 [95% CI: 0.44–0.84]). Median overall survival (OS) was 19.4 months for patients with a sustained high NLR, compared to 44.0 months for patients with a sustained low NLR (log-rank test p = 0.0011; HR 0.54 [95% CI: 0.38–0.77]).Conclusions:A sustained high NLR from baseline to mid-NAC is an independent prognostic factor for patients with MIBC.

Monitoring the neutrophil‐to‐lymphocyte ratio may be useful for predicting the anticancer effect of nivolumab in recurrent or metastatic head and neck cancer

“…Salim et al also reported that the NLR is an independent prognostic factor in patients with recurrent or metastatic HNSCC . On the other hand, previous studies suggested that the NLR predicts chemotherapy outcomes in patients with various types of cancer . Although the clinical benefit (SD + PR) were observed in some of the patients with pretreatment NLR of ≥5.0 as well as in patients with pretreatment NLR of <5.0, pretreatment NLR ≥5.0 is associated with worse survival in patients undergoing nivolumab monotherapy in this study.…”

Role of Systemic Inflammatory Response Markers in Urothelial Carcinoma

“…In MIBC (3), patients with high CRP before surgery have a significant correlation with adverse outcomes in treatment outcomes and survival. And NLR was relatively low in complete response and pathologic T0 in patients with high NLR before RC or before NAC (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). And increased NLR levels during 1-3 months post RC were associated with adverse survival outcomes (12).…”

“…Several studies have reported on the prognostic role of NLR in MIBC and metastatic BC ( Table 2) (24,41,(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Furthermore, several studies have reported on the role of prognostic factors in survival outcomes of MIBC and metastatic UC (24, 41, 47, 48, 50, 52-56, 59, 60), while other studies have suggested that the postoperative stages or disease severity can be predicted (Table 3) (41,48,49,58,(69)(70)(71)(72)(73).…”

Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC

“…In addition to local immunity, the peripheral absolute lymphocyte count has been associated with an inferior outcome in various cancers. 19 Furthermore, peripheral NLR has been postulated to be a prognostic factor for individuals with MIBC [26][27][28] and higher values of NLR have been associated with an increased risk of disease recurrence and overall survival in NMIBC. 29,30 In the present study and consistent with a recently published report, 39 a higher NLR prior to BCG treatment value was identified in BCG nonresponders, although the difference did not reach significance.…”

“…20 Furthermore, the neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammation and a strong predictor for prognosis in patients with different diseases, 21,22 has been suggested to be a prognostic predictor for overall survival and disease free survival and a predictive marker of the response to treatment in many cancers. 23 In bladder cancer, high NLR has been associated with poor clinical outcome in individuals with muscle-invasive bladder cancer (MIBC), 24,25 it has been postulated as a prognostic factor for individuals with MIBC undergoing neoadjuvant chemotherapy [26][27][28] and it correlates with disease progression and recurrence in individuals with NMIBC. 29,30 Overall, immune biomarkers based on TILs or blood cells have been independently described in cancer patients; however, the possibility that a combination of both factors could generate a more reliable prognostic biomarker has not previously been explored.…”