Is Neutrophil / Lymphocyte Ratio Really Significant in Small Renal Masses? Volume 51- Issue 4

Ibrahim Topçu* and Fatih Oğuz

• Inonu University, School of Medicine, Department of Urology, Turkey

Received: July 11, 2023;   Published: July 21, 2023

*Corresponding author: Ibrahim Topçu, Department of Urology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey

DOI: 10.26717/BJSTR.2023.51.008141

Abstract PDF

Background: In this study, patients who underwent partial nephrectomy through the nephron sparing surgery for renal mass in our clinic were retrospectively screened. We aimed to evaluate patients by preoperative neutrophil to lymphocyte ratio incidence and the relation with PADUA scoring system, which is the widely used nephrometry score.

Material and Method: 51 patients and 52 renal masses were included into the study. Significance test was performed in terms of preoperative neutrophil to lymphocyte ratios, PADUA scores, bleeding quantities, pathological types, and histological grades.

Results: No statistically significant difference was found in the histological grade, pathologic type, PADUA score, preoperative neutrophil to lymphocyte ratios in the statistical comparison of patients with partial nephrectomy. Only age together with tumor size and preoperative neutrophil to lymphocyte ratio together with bleeding amount significantly correlated.

Conclusions: Partial nephrectomy is a technique that can be safely performed especially in T1 early-stage tumors. However, we think that preoperative neutrophil / lymphocyte ratio cannot be used as a prognostic factor in early-stage tumors.

Keywords: Partial Nephrectomy; Renal Mass; PADUA; Nephrometry Score; Neutrophil / Lymphocyte Ratio; NLR: Neutrophil/Lymphocyte Ratio

Abbreviations: RCC: Renal Cell Carcinomas; PN: Partia Nephrectomy; PADUA: Preoperative Aspects and Dimensions Used for an Anatomical; SPSS: Statistical Package for Social Sciences

Renal tumors constitute 2-3% of all tumors in adulthood [1] and are more common in developed societies. Recently, the incidence of kidney tumors has been increasing with the more frequent use of imaging methods [2]. The most common renal tumors are Renal Cell Carcinomas (RCC), which constitutes approximately 85% of all kidney tumors [3]. Although 20-30% of patients with RCC are metastatic at the time of diagnosis, surgical intervention can be achieved in patients diagnosed at an early stage. However, metastases may occur in 20-40% of patients after surgery. Partial nephrectomy (PN) surgery is the recommended treatment method for T1a RCC [4], and some nephrometric scores have been developed to predict the complications that may occur in this surgical method and the prognosis of the disease. Among these scores, the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) system is most frequently used [5]. Despite the recent popularity of molecular factors to predict prognosis, no better predictor of prognosis than tumor stage and tumor grade has not been found yet. For this reason, different prognostic factors are being investigated. Neutrophil/lymphocyte ratio (NLR) is shown as a candidate among these prognostic factors. The basic idea in investigating this factor is that systemic inflammation plays an important role in preventing tumor development and metastasis [6]. It is known that with a systemic inflammatory reaction, the number of neutrophils in the peripheral blood increases and the number of lymphocytes decreases [7]. From this point of view, when the prognostic factor related to the neutrophil/lymphocyte ratio was investigated, it was found to be significant for some solid tumors [8] such as melanoma [9], lung adenocarcinoma [10], bladder tumor [11]. However, research for RCC is conflicting. In this study, we thought that NLR might be effective in predicting the prognosis in small renal masses, and we aimed to present our results.

Patients who applied to the urology outpatient clinic with renal mass between September 2013 and March 2018 were retrospectively scanned. Patients who underwent surgical partial nephrectomy and whose data could be fully accessed were included in the study and the patients that underwent radical nephrectomy, active surveillance/ palliative therapy, or whose data could not be fully accessed were excluded from the study (Figure 1). Demographic characteristics and laboratory findings of 51 patients and 52 renal units included in the study were obtained by retrospective scanning in Mergentech v2.18 Program, which is the hospital information management system. Preoperative images of kidney masses were obtained from the image archive of the Radiodiagnostics Department. During the evaluation, the side of the mass, its localization, its relationship with the renal sinus and collecting system, and surrounding tissues were examined, and PADUA scores were calculated. Pathological features were obtained from the pathology reports of the patients. Histological subtype, Fuhrman grade of the tumor, pathological size, condition of the surgical margin, tumor stage, sarcomatoid differentiation and coagulation necrosis were evaluated. The results were staged according to the 2017 TNM [12] staging, and the Fuhrman grading system was used for histological grading. Pathology results, PADUA scores and neutrophil lymphocyte ratios of the patients were evaluated by statistical significance.

Figure 1

Statistical Analysis

The analysis of all the obtained data was performed by saving it to the database created in the Windows Statistical Package for Social Sciences (SPSS v22.0) package program and taking the significance level as 0.05 at the 95% confidence interval. Conformity of continuous variables to normal distribution was investigated by Kolmogorov Smirnov Test. Data conforming to normal distribution were evaluated with Student’s t test, and data not conforming to the normal distribution were evaluated with Mann-Whitney U test. When evaluating dependent groups, those with normal distribution were analyzed with the t-test, and those that did not fit were analyzed with the Wilcoxon test. Statistical significance level was accepted as p=<0.05 in all analyzes.

Ethical Consent

Table 1: Demographic Characteristics of the Patients.

Note: COPD: Chronic Obstructive Pulmonary Disease, CAD: Coronary Artery Disease, DM: Diabetes Mellitus.

Of the 51 patients included in the study, 33 were male and 18 were female, and the mean age was 55.54 (28-84) years. 28 patients had at least one chronic disease. Fifteen of the patients had a history of smoking. In the statistical analysis, there was no significant difference between the presence of chronic disease and smoking with Fuhrman grade (p: 0.621), tumor size (p: 0.125), NLR (p: 0.269), and PADUA score (p: 0.802). The demographic characteristics of the patients are summarized in Table 1. 33 of the patients had right, 17 had left and 1 had bilateral renal mass. Laparoscopic surgery was performed in 5 patients and open partial nephrectomy in 47 patients. There was no significant difference in terms of bleeding between the patients who underwent both methods (p: 0.379).The mean size of the masses was 40 mm (13-100 mm), and the mean volume was calculated as 26.8 mm3 (1.05-157.3 mm3). Tumors were divided into 3 groups according to their size as ≤ 4 cm, 4-7 cm and > 7 cm. Sarcomatoid differentiation was not observed in any patient, but coagulation necrosis was positive in 5 patients and the mean NLR of these patients was calculated as 2.49, but it was not statistically significant (p: 0.662). Surgical margin was positive in 3 patients and their pathologies were clear cell RCC, papillary cell RCC type 1 and type 2. No local recurrence was observed in the follow-up of these patients. No significant difference was observed between the Fuhrman groups of tumors in terms of NLR. (p: 0.226). The pathological features of the patients are summarized in Table 2.

Table 2: Preoperative and Pathological Characteristics of the Tumor.

Note: *Fuhrman 1 and 2 low, 3 and 4 high grade. Fuhrman was not calculated in the chromophobe cell cancer group.

The mean NLR of the patients was calculated as 2.70 (0.91-15.11). The mean PADUA score of the tumors was calculated as 8.5 (6-11). In the PADUA scoring system, when 6 and 7 were grouped as low risk (n=11) and 8 and above as high risk (n=49), the NLR cut-off value was calculated as 1.63 according to Youden-J index (0.2328). The specificity of this value was 81.82%, and the sensitivity was 41.46%. The area under the ROC curve was calculated as 0.548 (Figure 2). However, no significant correlation was found between NLR and PADUA score. The mean postoperative hemoglobin losses of the patients were calculated as 1.56 g/dl (-1.5 - 4.9). When the NLR ratio and the amount of bleeding were compared, it was statistically significant that the amount of bleeding increased as the value increased (p:0.038). Retroperitoneal bleeding, a late complication, occurred in two of our patients and was controlled by angioembolization. Pseudoaneurysms were detected in both of their angiographies. Urine extravasation was also observed in one of the patients and DJ stent was placed and followed up. After that, the defect closed and the DJ stent was removed 1 month later.

Figure 2

Renal Cell Carcinomas (RCC) are generally seen in the 5th-7th decades and are approximately 2 times more common in men than women [13]. In our study, the mean age at diagnosis was 55.54 (28-84) and the male/female ratio was 1.83, similar to the literature.Its etiology is multifactorial, the main ones are smoking, obesity and hypertension. There is also a genetic predisposition [14]. 28 patients had at least one chronic disease, and 24 patients did not have any chronic disease in our study. 15 patients had a history of smoking. However, there was no statistically significant result between the presence of chronic disease and NLR in our study. RCC consists of 4 main subtypes, but sarcomatoid differentiation and coagulation necrosis show a poor prognosis in all subtypes, regardless of the type [15]. In our study, the mean NLR of patients with positive coagulation necrosis was calculated as 2.49, and this value was not statistically significant when compared with other patients (p: 0.662). Fuhrman nuclear grading system is also a prognostic factor independent of histological subtype [16]. There are 4 categories in this system and the prognosis worsens as the degree increases. However, some studies argue that the Fuhrman rating system should be replaced with a 2- or 3-layer system [17-21]. When we evaluated our patients by grouping them according to the 2-layer grading system, there was no significant difference with NLR (p: 0.226). In a meta-analysis conducted on approximately 40,000 patients with solid tumors, it was found that cancer-specific survival was significantly reduced, and recurrence-free life was shortened in patients with a NLR above 4 as an indicator of the systemic inflammatory response [22].

In a study conducted by Wassim et al. in 2016, 1970 patients with clear cell RCC were investigated and it was found that NLR was significantly associated with overall survival, cancer-specific survival, and ASA score, but when prognostic factors were added to these results, the risk was not affected [23]. In another study conducted by Martino et al. on patients with non-clear cell RCC, the NLR significance ratio was calculated as 2.6, and it was shown that disease-free survival decreased by 15% for each 1-unit increase over 2.625. Otunctemur et al. evaluated 432 patients who underwent radical or partial nephrectomy for RCC and found that NLR increased significantly with the increase in tumor stage and histological grade [24]. In a study by Görgel et al., it was found that there was a significant difference in terms of neutrophil/lymphocyte ratios between patients with benign and malignant tumors in patients with localized RCC and therefore partial nephrectomy [25]. However, in these studies, patients who underwent partial nephrectomy and those with malignant tumors were not evaluated in terms of tumor stage and histological prognostic factors and the significance of NLR. In our study, the pathology of the patients who underwent partial nephrectomy and those with RCC were evaluated within themselves. However, no statistically significant correlation was found between NLR and tumor stage, histological grade, and PADUA stage.

According to previous studies, NLR, which is an indicator of systemic inflammatory response, may be a prognostic factor in advanced solid tumors, but it is insufficient for its use in early-stage tumors. In our study, no significant correlation was found between NLR and PADUA score, so NLR should not be used as a prognostic factor in early stage RCC cases.

The authors report no conflict of interest.

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