Preoperative Systemic Inflammatory Markers as a Significant Prognostic Factor After TURBT in Patients with Non-Muscle-Invasive Bladder Cancer

Figures & data

Table 1 Baseline Demographics & Clinical Characteristics of Study Population

Variables	Level	Training Cohort (n=292)	Validation Cohort (n=124)
Gender, n (%)	Female	47(16.096)	15(12.097)
	Male	245(83.904)	109(87.903)
BMI (kg/m^2), n (%)	<25	177(60.616)	70(56.452)
	≥25	115(39.384)	54(43.548)
T category, n (%)	Ta	175(59.932)	73(58.871)
	T1	117(40.068)	51(41.129)
Prior recurrence status, n (%)	Primary	254(86.986)	105(84.677)
	Recurrent	38(13.014)	19(15.323)
Pathology grade, n (%)	Low-grade	124(42.466)	49(39.516)
	High-grade	168(57.534)	75(60.484)
Tumor number, n (%)	Single	134(45.890)	52(41.935)
	Multiple	158(54.110)	72(58.065)
Bladder neck invasion, n (%)	No	246(84.247)	101(81.452)
	Yes	46(15.753)	23(18.548)
Smoking status, n (%)	No	185(63.356)	76(61.290)
	Yes	107(36.644)	48(38.710)
Smoking years, n (%)	0	185(63.356)	76(61.290)
	<30	49(16.781)	18(14.516)
	≥30	58(19.863)	30(24.194)
Cigarettes per day, n (%)	0	185(63.356)	76(61.290)
	<30	96(32.877)	38(30.645)
	≥30	11(3.767)	10(8.065)
Age (year), median [IQR]		66[58, 74]	69[58, 75]
Maximum tumor diameter (millimeter), median [IQR]		20[15, 30]	20[14, 29]
Neutrophil count (×10^9/L), median [IQR]		3.480[2.790, 4.630]	3.480[2.780, 4.290]
Lymphocyte count (×10^9/L), median [IQR]		1.800[1.400, 2.300]	1.800[1.400, 2.400]
Monocyte count (×10^9/L), median [IQR]		0.430[0.340, 0.530]	0.450[0.340, 0.570]
Platelet count (×10^9/L), median [IQR]		217[181, 255]	204[175, 241]
NLR, median [IQR]		1.863[1.429, 2.670]	1.776[1.443, 2.640]
PLR, median [IQR]		113.700[90, 151.429]	115.130[83.125, 148.800]
LMR, median [IQR]		4.348[3.265, 5.510]	4.167[3.110, 5.806]

Abbreviations: BMI, body mass index, weight/height^2; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; IQR, inter-quartile range.

Table 2 Demographics & Clinical Characteristics According to NLR, PLR and LMR in the Training Cohort

Variables	Level	NLR<2.12 (n=180)	NLR≥2.12 (n=112)	p	PLR<175.71 (n=250)	PLR≥175.71 (n=42)	p	LMR<4.58 (n=165)	LMR≥4.58 (n=127)	p
Gender, n (%)	Female	33(18.333)	14(12.500)	0.187	37(14.800)	10(23.810)	0.142	22(13.333)	25(19.685)	0.143
	Male	147(81.667)	98(87.500)		213(85.200)	32(76.190)		143(86.667)	102(80.315)
BMI (kg/m^2), n (%)	<25	104(57.778)	73(65.179)	0.208	148(59.200)	29(69.048)	0.227	107(64.848)	70(55.118)	0.092
	≥25	76(42.222)	39(34.821)		102(40.800)	13(30.952)		58(35.152)	57(44.882)
T category, n (%)	Ta	114(63.333)	61(54.464)	0.133	153(61.200)	22(52.381)	0.281	91(55.152)	84(66.142)	0.057
	T1	66(36.667)	51(45.536)		97(38.800)	20(47.619)		74(44.848)	43(33.858)
Prior recurrence status, n (%)	Primary	157(87.222)	97(86.607)	0.879	216(86.400)	38(90.476)	0.468	142(86.061)	112(88.189)	0.592
	Recurrent	23(12.778)	15(13.393)		34(13.600)	4(9.524)		23(13.939)	15(11.811)
Pathology grade, n (%)	Low-grade	74(41.111)	50(44.643)	0.553	105(42)	19(45.238)	0.694	70(42.424)	54(42.520)	0.987
	High-grade	106(58.889)	62(55.357)		145(58)	23(54.762)		95(57.576)	73(57.480)
Tumor number, n (%)	Single	86(47.778)	48(42.857)	0.412	120(48)	14(33.333)	0.078	71(43.030)	63(49.606)	0.264
	Multiple	94(52.222)	64(57.143)		130(52)	28(66.667)		94(56.970)	64(50.394)
Bladder neck invasion, n (%)	No	153(85)	93(83.036)	0.654	212(84.800)	34(80.952)	0.527	139(84.242)	107(84.252)	0.998
	Yes	27(15)	19(16.964)		38(15.200)	8(19.048)		26(15.758)	20(15.748)
Smoking status, n (%)	No	109(60.556)	76(67.857)	0.208	153(61.200)	32(76.190)	0.062	110(66.667)	75(59.055)	0.181
	Yes	71(39.444)	36(32.143)		97(38.800)	10(23.810)		55(33.333)	52(40.945)
Smoking years, n (%)	0	109(60.556)	76(67.857)	0.443	153(61.200)	32(76.190)	0.167	110(66.667)	75(59.055)	0.407
	<30	32(17.778)	17(15.179)		45(18)	4(9.524)		25(15.152)	24(18.898)
	≥30	39(21.667)	19(16.964)		52(20.800)	6(14.286)		30(18.182)	28(22.047)
Cigarettes per day, n (%)	0	109(60.556)	76(67.857)	0.407	153(61.200)	32(76.190)	-	110(66.667)	75(59.055)	0.232
	<30	63(35)	33(29.464)		86(34.400)	10(23.810)		51(30.909)	45(35.433)
	≥30	8(4.444)	3(2.679)		11(4.400)	0(0)		4(2.424)	7(5.512)
Age (year), median [IQR]		65[55, 73]	68[63, 76]	0.008	66[57, 74]	64[59, 76]	0.867	67[59, 76]	65[55, 72]	0.016
Maximum tumor diameter (mm), median [IQR]		20[14, 30]	21[15, 30]	0.1	20[14, 30]	25[17, 35]	0.02	20[15, 30]	20[14, 27]	0.172

Abbreviations: BMI, body mass index, weight/height^2; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; IQR, inter-quartile range.

Table 3 Demographics & Clinical Characteristics According to SMI Score in the Training Cohort

Variables	Level	SIM Score=0 (n=111)	SIM Score=1 (n=77)	SIM Score=2 (n=70)	SIM Score=3 (n=34)	p
Gender, n (%)	Female	21(18.919)	12(15.584)	8(11.429)	6(17.647)	0.602
	Male	90(81.081)	65(84.416)	62(88.571)	28(82.353)
BMI, n (%)	<25	60(54.054)	48(62.338)	46(65.714)	23(67.647)	0.313
	≥25	51(45.946)	29(37.662)	24(34.286)	11(32.353)
T category, n (%)	Ta	74(66.667)	46(59.740)	37(52.857)	18(52.941)	0.236
	T1	37(33.333)	31(40.260)	33(47.143)	16(47.059)
Prior recurrence status, n (%)	Primary	99(89.189)	64(83.117)	60(85.714)	31(91.176)	0.548
	Recurrent	12(10.811)	13(16.883)	10(14.286)	3(8.824)
Pathology grade, n (%)	Low-grade	44(39.640)	37(48.052)	27(38.571)	16(47.059)	0.557
	High-grade	67(60.360)	40(51.948)	43(61.429)	18(52.941)
Tumor number, n (%)	Single	60(54.054)	28(36.364)	33(47.143)	13(38.235)	0.084
	Multiple	51(45.946)	49(63.636)	37(52.857)	21(61.765)
Bladder neck invasion, n (%)	No	92(82.883)	69(89.610)	58(82.857)	27(79.412)	0.471
	Yes	19(17.117)	8(10.390)	12(17.143)	7(20.588)
Smoking status, n (%)	No	66(59.459)	47(61.039)	45(64.286)	27(79.412)	0.195
	Yes	45(40.541)	30(38.961)	25(35.714)	7(20.588)
Smoking years, n (%)	0	66(59.459)	47(61.039)	45(64.286)	27(79.412)	0.358
	<30	20(18.018)	16(20.779)	9(12.857)	4(11.765)
	≥30	25(22.523)	14(18.182)	16(22.857)	3(8.824)
Cigarettes per day, n (%)	0	66(59.459)	47(61.039)	45(64.286)	27(79.412)	-
	<30	39(35.135)	27(35.065)	23(32.857)	7(20.588)
	≥30	6(5.405)	3(3.896)	2(2.857)	0(0)
Age, median [IQR]		65[55, 71]	69[58, 75]	67[63, 78]	64[59, 76]	0.029
Maximum tumor diameter, median [IQR]		20[13, 27]	20[15, 30]	20[15, 30]	25[18, 35]	0.084

Abbreviations: BMI, body mass index, weight/height^2; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; SMI, systemic inflammatory markers; IQR, inter-quartile range.

Figure 1 The Kaplan-Meier analysis of RFS stratified by (A) NLR, (B) PLR, (C) LMR; and the Kaplan-Meier analysis of PFS stratified by (D) NLR, (E) PLR, (F) LMR in the training cohort.

Figure 2 The Kaplan-Meier analysis of (A) RFS and (B) PFS stratified by SIM score in the training cohort.

Table 4 Univariable and Multivariable Analysis for Predicting Recurrence-Free Survival

Variables	Univariate HR	95% CI	p	Multivariate HR	95% CI	p
Age	0.998	[0.982, 1.015]	0.843
Maximum tumor diameter	1.016	[1.000, 1.033]	0.056
Gender			0.259
Female	1(reference)
Male	1.491	[0.745, 2.982]
BMI			0.189
<25	1(reference)
≥25	0.732	[0.459, 1.167]
T category			0.013			0.294
Ta	1(reference)			1(reference)
T1	1.729	[1.120, 2.669]		1.291	[0.801, 2.08]
Prior recurrence status			0.001			0.001
Primary	1(reference)			1(reference)
Recurrent	2.461	[1.465, 4.134]		2.564	[1.479, 4.446]
Pathology grade			0.039			0.217
Low-grade	1(reference)			1(reference)
High-grade	1.628	[1.024, 2.589]		1.379	[0.828, 2.299]
Tumor number			0.003			0.008
Single	1(reference)			1(reference)
Multiple	2.045	[1.274, 3.283]		1.968	[1.196, 3.237]
Bladder neck invasion			0.003			0.533
No	1(reference)			1(reference)
Yes	2.133	[1.295, 3.513]		1.194	[0.684, 2.083]
SIM score			0.003			0.002
0	1(reference)			1(reference)
1	1.235	[0.675, 2.258]	0.494	1.118	[0.601, 2.083]	0.724
2	1.672	[0.942, 2.966]	0.079	1.583	[0.881, 2.844]	0.124
3	3.265	[1.726, 6.177]	<0.001	3.323	[1.732, 6.375]	<0.001
Smoking status			0.256
No	1(reference)
Yes	1.292	[0.830, 2.009]
Smoking years			0.419
0	1(reference)
<30	1.447	[0.830, 2.523]	0.193
≥30	1.167	[0.670, 2.033]	0.585
Cigarettes per day			0.209
0	1(reference)
<30	1.204	[0.758, 1.914]	0.432
≥30	2.238	[0.887, 5.648]	0.088

Abbreviations: BMI, body mass index, weight/height^2; SMI, systemic inflammatory markers; N, number of patients; HR, hazard ratio; CI, confidence interval.

Table 5 Univariable and Multivariable Analysis for Predicting Progression-Free Survival

Variables	Univariate HR	95% CI	p	Multivariate HR	95% CI	p
Age	0.999	[0.978, 1.021]	0.94
Maximum tumor diameter	1.026	[1.004, 1.048]	0.018	1.01	[0.988, 1.033]	0.382
Gender			0.106
Female
Male	2.633	[0.815, 8.502]
BMI			0.908
<25
≥25	0.965	[0.527, 1.767]
T category			0.002			0.353
Ta				1(reference)
T1	2.642	[1.444, 4.835]		1.371	[0.705, 2.67]
Prior recurrence status			<0.001			0.003
Primary				1(reference)
Recurrent	3.188	[1.665, 6.104]		3.172	[1.491, 6.75]
Pathology grade			0.001			0.016
Low-grade				1(reference)
High-grade	3.395	[1.631, 7.067]		2.644	[1.195, 5.851]
Tumor number			0.001			0.002
Single				1(reference)
Multiple	3.22	[1.592, 6.516]		3.325	[1.551, 7.129]
Bladder neck invasion			<0.001			0.329
No				1(reference)
Yes	3.447	[1.865, 6.370]		1.415	[0.704, 2.844]
SIM score			0.001			0.001
0				1(reference)
1	1.171	[0.470, 2.916]	0.735	1.139	[0.443, 2.934]	0.787
2	2.459	[1.129, 5.357]	0.024	2.564	[1.143, 5.755]	0.022
3	5.098	[2.190, 11.871]	<0.001	5.354	[2.185, 13.121]	<0.001
Smoking status			0.144
No
Yes	1.549	[0.862, 2.784]
Smoking years			0.261
0	1(reference)
<30	1.798	[0.880, 3.676]	0.108
≥30	1.344	[0.643, 2.813]	0.432
Cigarettes per day			0.192
0	1(reference)
<30	1.448	[0.785, 2.669]	0.236
≥30	2.682	[0.801, 8.973]	0.109

Abbreviations: BMI, body mass index, weight/height^2; SMI, systemic inflammatory markers; N, number of patients; HR, hazard ratio; CI, confidence interval.

Figure 3 (A) The nomogram for predicting RFS after TURBT for NMIBC. (B) Time-dependent ROC curves of the nomogram for predicting RFS in the training cohort. (C) Calibration plot of the nomogram by bootstrapping with 1000 resamples for predicting RFS in the training cohort. (D) Decision-curve analyses demonstrating the net benefit associated with the use of the model for predicting RFS.

Figure 4 (A) The nomogram for predicting PFS after TURBT for NMIBC. (B) Time-dependent ROC curves of the nomogram for predicting PFS. (C) Calibration plot of the nomogram by bootstrapping with 1000 resamples for predicting PFS. (D) Decision-curve analyses demonstrating the net benefit associated with the use of the model for predicting PFS.

Figure 5 (A) Time-dependent ROC curves of the nomogram for predicting RFS in the validation cohort in the validation cohort. (B) Calibration plot of the nomogram by bootstrapping with 1000 resamples for predicting RFS in the validation cohort in the validation cohort. (C) Time-dependent ROC curves of the nomogram for predicting PFS in the validation cohort in the validation cohort. (D) Calibration plot of the nomogram by bootstrapping with 1000 resamples for predicting PFS in the validation cohort in the validation cohort.

Figure 6 The Kaplan-Meier curves of low-risk and high-risk groups based on the prediction of the nomogram models for (A) RFS and (B) PFS.