Preoperative Inflammation-Associated Blood Cell Markers in Patients with Non-Metastatic Clear Cell Renal Cell Carcinoma: A Retrospective Study

Figures & data

Table 1 Clinicopathologic Features of the Cohort

Characteristic	Value
Patients, n	444
Preoperative clinical
Median age at surgery, year (IQR)	58 (51–65)
Male sex (%)	311 (70.0)
Smoking history (%)	138 (31.1)
Alcohol history (%)	90 (20.3)
Hypertension (%)	207 (46.6)
Diabetes (%)	81 (18.2)
Median BMI (kg/m^2) (IQR)	24.2 (22.1–26.4)
ECOG performance status (%)
0	302 (68.0)
≥1	142 (32.0)
Charlson Comorbidity Index
0–1	386 (86.9)
≥2	58 (13.1)
Surgical
Type of treatment (%)
Partial	137 (30.9)
Radical	307 (69.1)
Surgical approach (%)
Open	11 (2.5)
Laparoscopic	364 (82.0)
Da Vinci robot	69 (15.5)
Pathologic
Grade (%)
1	22 (5.0)
2	314 (70.7)
3	88 (19.8)
4	20 (4.5)
pT-classification (%)
pT1	370 (83.3)
pT2	23 (5.2)
pT3	18 (4.1)
pT4	33 (7.4)
pN-classification (%)
pN0	442 (99.5)
pN1	2 (0.5)
Median pathologic tumor size (IQR)	3.5 (2.6–5.0)
Pathological necrosis (%)	31 (7.0)
Preoperative hematologic index
Hemoglobin, g/dL	139 (129.3–149.0)
WBC, 10^9/L	6.0 (5.0–7.0)
Neutrophil count, 10^9/L	3.5 (2.9–4.3)
Lymphocyte count, 10^9/L	1.7 (1.4–2.1)
Monocyte count, 10^9/L	0.4 (0.4–0.6)
NLR	2.0 (1.6–2.6)
PLR	112.9 (87.1–143.9)
LMR	3.8 (3.0–5.0)
RDW	13.2 (12.9–13.7)
Risk group
UISS risk group, n (%)
Low	210 (47.3)
Intermediate	194 (43.7)
High	40 (9.0)
SSIGN risk group, n (%)
Low (0–2)	363 (81.8)
Intermediate (3–5)	70 (16.0)
High (≥6)	10 (2.3)

Note: Data presented as median (IQR) or n (%).

Abbreviations: BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range; WBC, white blood cell; NLR, Neutrophil-to-Lymphocyte Ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; RDW, red blood cell distribution width; UISS, University of California, Los Angeles, integrated staging system; SSIGN, the stage, size, grade, and necrosis (SSIGN) score.

Table 2 The Clinical and Pathological Characteristics of Different Groups

Variable	NLR			PLR			LMR			RDW
	<3.4	≥3.4	P value	<157.3	≥157.3	P value	<2.7	≥2.7	P value	<13.1	≥13.1	P value
Age			0.016*			0.045*			0.003*			0.570
<65	282 (71.2)	26 (54.2)		258 (71.5)	50 (60.2)		43 (55.1)	265 (72.4)		122 (70.9)	186 (68.4)
≥65	114 (28.8)	22 (45.8)		103 (28.5)	33 (39.8)		35 (44.9)	101 (27.6)		50 (29.1)	86 (31.6)
Male gender	274 (69.2)	37 (77.1)	0.260	255 (70.6)	56 (67.5)	0.570	62 (79.5)	249 (68.0)	0.045*	122 (70.9)	189 (69.5)	0.746
Smoking	117 (29.5)	21 (43.8)	0.045*	114 (31.6)	24 (28.9)	0.636	33 (42.3)	105 (28.7)	0.018*	46 (26.7)	92 (33.8)	0.116
Alcohol	82 (20.7)	8 (16.7)	0.511	75 (20.8)	15 (18.1)	0.581	15 (19.2)	75 (20.5)	0.801	38 (22.1)	52 (19.1)	0.447
Diabetes	68 (17.2)	13 (27.1)	0.093	66 (18.3)	15 (18.1)	0.964	19 (24.4)	62 (16.9)	0.123	35 (20.3)	46 (16.9)	0.361
Hypertension	180 (45.5)	27 (56.3)	0.157	166 (46.0)	41 (49.4)	0.574	44 (56.4)	163 (44.5)	0.056	77 (44.8)	130 (47.8)	0.533
BMI			0.747			0.030*			0.478			0.996
<24	183 (46.2)	21 (43.8)		157 (43.5)	47 (56.6)		33 (42.3)	171 (46.7)		79 (45.9)	127 (46.0)
≥24	213 (53.8)	27 (56.3)		204 (56.5)	36 (43.4)		45 (57.7)	195 (53.3)		93 (54.1)	145 (54.0)
ECOG			0.232			0.522			0.177			0.297
0	273 (68.9)	29 (60.4)		248 (68.7)	54 (65.1)		48 (61.5)	254 (69.4)		112 (65.1)	190 (69.9)
≥1	123 (31.1)	19 (39.6)		113 (31.3)	29 (34.9)		30 (38.5)	112 (30.6)		60 (34.9)	82 (30.1)
CCI			0.032*			0.254			0.032*			0.878
0–1	349 (88.1)	37 (77.1)		317 (87.8)	69 (83.1)		62 (79.5)	324 (88.5)		149 (86.6)	237 (87.1)
≥2	47 (11.9)	11 (22.9)		44 (12.2)	14 (16.9)		16 (20.5)	42 (11.5)		23 (13.4)	35 (12.9)
Pathologic tumor size, cm			0.021*			0.117			0.086			0.031*
<4	210 (53.0)	17 (35.4)		191 (52.9)	36 (43.4)		33 (42.3)	194 (53.0)		99 (57.6)	128 (47.1)
≥4	186 (47.0)	31 (64.6)		170 (47.1)	47 (56.6)		45 (57.7)	172 (47.0)		73 (42.4)	144 (52.9)
Pathological tumor stage			0.095			0.576			0.049*			0.493
pT1-pT2	354 (89.4)	39 (81.3)		321 (88.9)	72 (86.7)		64 (82.1)	329 (89.9)		150 (87.2)	243 (89.3)
pT3-pT4	42 (10.6)	9 (18.8)		40 (11.1)	11 (13.3)		14 (17.9)	37 (10.1)		22 (12.8)	29 (10.7)
Pathological node stage			1.000			1.000			0.321			1.000
pN0	394 (99.5)	48 (100)		359 (99.4)	83 (100)		77 (98.7)	365 (99.7)		171 (99.4)	271 (99.6)
pN1	2 (0.5)	0 (0)		2 (0.6)	0 (0)		1 (1.3)	1 (0.3)		1 (0.6)	1 (0.4)
Fuhrman grade			0.009*			0.012*			0.001*			0.623
1–2	307 (77.5)	29 (60.4)		282 (78.1)	54 (65.1)		48 (61.5)	288 (78.7)		128 (74.4)	208 (76.5)
3–4	89 (22.5)	19 (39.6)		79 (21.9)	29 (34.9)		30 (38.5)	78 (21.3)		44 (25.6)	64 (23.5)
Tumor necrosis	25 (6.3)	6 (12.5)	0.198	24 (6.6)	7 (8.4)	0.565	8 (10.3)	23 (6.3)	0.211	17 (9.9)	14 (5.1)	0.056
UISS risk group			0.041*			0.269			0.009*			0.459
Low	191 (48.2)	19 (39.6)		175 (48.5)	35 (42.2)		32 (41.0)	178 (48.6)		75 (43.6)	135 (49.6)
Intermediate	174 (43.9)	20 (41.7)		157 (43.5)	37 (44.6)		32 (41.0)	162 (44.3)		80 (46.5)	114 (41.9)
High	31 (7.8)	9 (18.8)		29 (8.0)	11 (13.3)		14 (17.9)	26 (7.1)		17 (9.9)	23 (8.5)
SSIGN risk group			0.022*			0.001*			<0.001*			0.335
Low (0–2)	330 (83.3)	33 (68.8)		307 (85.0)	56 (67.5)		52 (66.7)	311 (85.0)		137 (79.7)	226 (83.1)
Intermediate (3–5)	59 (14.9)	12 (25.0)		48 (13.3)	23 (27.7)		21 (26.9)	50 (13.7)		29 (16.9)	42 (15.4)
High (≥6)	7 (1.8)	3 (6.3)		6 (1.7)	4 (4.8)		5 (6.4)	5 (1.4)		6 (3.5)	4 (1.5)

Notes: Data presented as n (%). *Statistically significant.

Abbreviations: NLR, Neutrophil-to-Lymphocyte Ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; RDW, red blood cell distribution width; BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; CCI, Charlson Comorbidity Index; UISS, University of California, Los Angeles, integrated staging system; SSIGN, the stage, size, grade, and necrosis (SSIGN) score.

Table 3 Predictors of Recurrence Free, Cancer-Specific and Overall Survival

Variable	Recurrence-Free Survival				Cancer-Specific Survival				Overall Survival
	Univariate		Multivariate		Univariate		Multivariate		Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age		0.282				0.171				0.018		0.091
<65	Reference				Reference				Reference		Reference
≥65	1.34 (0.79–2.30)				1.68 (0.80–3.52)				2.15 (1.14–4.07)		1.79 (0.91–3.50)
Gender	0.60 (0.32–1.13)	0.114			0.73 (0.31–1.70)	0.462			0.84 (0.41–1.73)	0.632
Smoking	1.02 (0.59–1.79)	0.933			1.04 (0.47–2.29)	0.922			0.92 (0.46–1.86)	0.819
Alcohol	1.43 (0.80–2.58)	0.229			1.04 (0.42–2.56)	0.932			0.74 (0.31–1.77)	0.495
Diabetes	0.96 (0.50–1.86)	0.912			0.85 (0.35–2.10)	0.731			0.71 (0.34–1.50)	0.365
Hypertension	1.37 (0.82–2.29)	0.233			1.44 (0.69–3.00)	0.327			1.78 (0.93–3.42)	0.082
BMI		0.909				0.146				0.339
<24	Reference				Reference				Reference
≥24	1.03 (0.61–1.73)				0.58 (0.28–1.21)				0.73 (0.39–1.39)
ECOG		0.015*		0.456		0.007*		0.893		0.005		0.301
0	Reference		Reference		Reference		Reference		Reference		Reference
≥1	1.90 (1.13–3.19)		1.24 (0.71–2.18)		2.76 (1.33–5.74)		0.94 (0.39–2.28)		2.48 (1.31–4.69)		1.46 (0.71–2.99)
CCI		0.879				0.510				0.314
0–1	Reference				Reference				Reference
≥2	1.06 (0.50–2.24)				1.38 (0.53–3.63)				1.52 (0.67–3.46)
Pathologic tumor size, cm		0.004		0.753		0.001		0.252		0.002		0.283
<4	Reference		Reference		Reference		Reference		Reference		Reference
≥4	2.19 (1.28–3.77)		1.10 (0.61–2.00)		5.32 (2.03–13.93)		1.86 (0.65–5.35)		3.17 (1.54–6.52)		1.54 (0.70–3.41)
Pathological tumor stage		<0.001*		0.001*		<0.001*		<0.001*		<0.001*		<0.001*
pT1-pT2	Reference		Reference		Reference		Reference		Reference		Reference
pT3-pT4	4.07 (2.31–7.16)		2.78 (1.50–5.18)		7.65 (3.67–15.93)		5.61 (2.42–13.02)		5.63 (2.91–10.90)		4.50 (2.17–9.34)
Pathological node stage		<0.001*		0.111		0.008		0.281		0.027		0.436
pN0	Reference		Reference		Reference		Reference		Reference		Reference
pN1	15.64 (3.80–64.32)		3.59 (0.75–7.27)		14.86 (2.01–110.00)		3.37 (0.37–30.57)		9.53 (1.30–69.85)		2.37 (0.27–20.71)
Fuhrman grade		<0.001*		<0.001*		<0.001*		0.004*		<0.001*		0.068
1–2	Reference		Reference		Reference		Reference		Reference		Reference
3–4	6.19 (3.65–10.50)		3.83 (2.10–7.02)		11.57 (4.93–27.16)		4.22 (1.57–11.35)		4.99 (2.62–9.52)		2.07 (0.95–4.54)
Tumor necrosis	5.24 (2.82–9.74)	<0.001*	2.18 (1.08–4.40)	0.029*	10.28 (4.83–21.87)	<0.001*	3.22 (1.30–8.00)	0.012*	6.29 (3.04–13.01)	<0.001*	2.39 (1.01–5.64)	0.048*
NLR		<0.001*		0.115		<0.001*		0.001*		<0.001*		0.001*
<3.4	Reference		Reference		Reference		Reference		Reference		Reference
≥3.4	3.02 (1.63–5.60)		1.80 (0.87–3.74)		7.14 (3.40–15.02)		5.40 (2.03–14.36)		5.28 (2.69–10.35)		4.42 (1.88–10.40)
PLR		0.001*		0.285		<0.001*		0.067		<0.001*		0.051
<157.3	Reference		Reference		Reference		Reference		Reference		Reference
≥157.3	2.44 (1.41–4.22)		1.43 (0.74–2.77)		4.37 (2.11–9.06)		2.38 (0.94–6.02)		3.45 (1.81–6.58)		2.18 (1.00–4.74)
LMR		<0.001*		0.101		0.003*		0.435		0.014*		0.179
<2.7	Reference		Reference		Reference		Reference		Reference		Reference
≥2.7	0.32 (0.19–0.55)		0.57 (0.30–1.12)		0.31 (0.15–0.67)		1.47 (0.56–3.83)		0.42 (0.21–0.84)		1.83 (0.76–4.42)
RDW		0.512				0.628				0.595
<13.1	Reference				Reference				Reference
≥13.1	0.84 (0.50–1.41)				1.21 (0.56–2.60)				1.20 (0.61–2.35)

Note: *Statistically significant.

Abbreviations: HR (95% CI), Hazard Ratio (95% confidence interval); BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; CCI, Charlson Comorbidity Index; NLR, Neutrophil-to-Lymphocyte Ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; RDW, red blood cell distribution width.

Figure 1 Kaplan-Meier curves were generated to assess the recurrence-free survival, cancer-specific survival, and overall survival based on the values of NLR, PLR, LMR, and RDW.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; RDW, red blood cell distribution; RFS, recurrence-free survival; CSS, cancer-specific survival; OS, overall survival.

Table 4 Univariate and Multivariate Cox Regression Models Incorporating Prognostic Risk Models and NLR in Prediction of Cancer-Specific Survival, and Overall Survival

Variable	Cancer-Specific Survival				Overall Survival
	Univariate Model		Multivariate Model		Univariate Model		Multivariate Model
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
UISS risk group
Low	Reference		Reference		Reference		Reference
Intermediate	5.03 (1.43–17.68)	0.012*	4.82 (1.37–16.92)	0.014*	2.97 (1.24–7.12)	0.015*	2.92 (1.22–7.00)	0.016
High	30.42 (8.65–106.93)	<0.001*	29.03 (8.22–102.53)	<0.001*	13.39 (5.33–33.63)	<0.001*	13.01 (5.16–32.81)	<0.001*
NLR		<0.001*		<0.001*
<3.4	Reference		Reference		Reference		Reference
≥3.4	7.14 (3.40–15.02)		6.72 (3.16–14.28)		5.28 (2.69–10.35)	<0.001*	5.09 (2.58–10.03)	<0.001*
SSIGN risk group
Low	Reference		Reference		Reference		Reference
Intermediate	9.78 (4.28–22.39)	<0.001*	8.45 (3.67–19.44)	<0.001*	5.78 (2.95–11.34)	<0.001*	5.22 (2.65–10.28)	<0.001*
High	36.27 (11.95–110.06)	<0.001*	27.46 (8.96–84.15)	<0.001*	15.94 (5.30–47.92)	<0.001*	12.22 (4.03–37.10)	<0.001*
NLR
<3.4	Reference		Reference		Reference		Reference
≥3.4	7.14 (3.40–15.02)	<0.001*	5.08 (2.40–10.78)	<0.001*	5.28 (2.69–10.35)	<0.001*	4.17 (2.11–8.25)	<0.001*

Note: *Statistically significant.

Abbreviations: HR (95% CI), Hazard Ratio (95% confidence interval); NLR, Neutrophil-to-Lymphocyte Ratio; UISS, University of California, Los Angeles, integrated staging system; SSIGN, the stage, size, grade, and necrosis (SSIGN) score.