World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 2, April 2024, pages 287-297

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma

Figure 1. Elevated TG, CHOL, and reduced HDL had significant worse OS as revealed by Kaplan-Meier analysis and log-rank test (P < 0.05). TG: triacylglycerol; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; OS: overall survival.

Figure 2. Elevated CHOL, LDL, TG and reduced HDL were associated with significantly worse PFS, as indicated by Kaplan-Meier analysis and log-rank test (P < 0.05). TG: triacylglycerol; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; PFS: progression-free survival.

Figure 3. The Kaplan-Meier analysis and log rank test showed significantly worse CSS in elevated TG and CHOL (P < 0.05). TG: triacylglycerol; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; CSS: cancer-specific survival.

**Table 1.** Clinical Characteristic of UTUC Patients Receiving RNU
Variables	Number of patients (%) (n = 217)	Median (Q1 - Q3)
RNU: radical nephroureterectomy; UTUC: upper tract urothelial carcinoma; BMI: body mass index; CCI: Charlson Comorbidity Index; DM: diabetes mellitus; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.
Age		71 (63 - 76)
Gender
Male	98 (45.16)
Female	119 (54.84)
BMI		24.3 (21.92 - 26.93)
CCI		5 (4 - 6)
Smoking
Yes	37 (17.05)
No	180 (82.95)
DM
Yes	83 (38.25)
No	134 (61.75)
Hypertension
Yes	177 (81.57)
No	40 (18.43)
Grade
Low	25 (11.52)
High	192 (88.48)
T stage
Tis/Ta/T1	106 (48.85)
T2/T3/T4	111 (51.15)
Nodal status
N0/Nx	207 (95.39)
N1/N2	10 (4.61)
Initial metastasis
Yes	5 (2.3)
No	212 (97.7)
Multifocality
Yes	34 (15.67)
No	183 (84.33)
Size
< 3cm	97 (44.7)
≥ 3cm	120 (55.3)
Squamous differentiation
Yes	5 (2.3)
No	212 (97.7)
Free resection margin
Yes	208 (95.85)
No	9 (4.15)
Adjuvant therapy
Yes	44 (20.28)
No	173 (79.72)
CHOL		170 (144 - 193)
< 200	177 (81.57)
≥ 200	40 (18.43)
HDL		43.8 (35.7 - 56.4)
< 40 (men), < 50 (female)	107 (49.31)
≥ 40 (men), ≥ 50 (female)	110 (50.69)
LDL		93.6 (75.3 - 114)
< 130	185 (85.25)
≥ 130	32 (14.75)
TG		103 (78 - 150)
< 150	162 (74.65)
≥ 150	55 (25.35)

Table 1. Clinical Characteristic of UTUC Patients Receiving RNU

Variables

Number of patients (%) (n = 217)

Median (Q1 - Q3)

RNU: radical nephroureterectomy; UTUC: upper tract urothelial carcinoma; BMI: body mass index; CCI: Charlson Comorbidity Index; DM: diabetes mellitus; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.

Age

71 (63 - 76)

Gender

Male

98 (45.16)

Female

119 (54.84)

BMI

24.3 (21.92 - 26.93)

CCI

5 (4 - 6)

Smoking

Yes

37 (17.05)

180 (82.95)

Yes

83 (38.25)

134 (61.75)

Hypertension

Yes

177 (81.57)

40 (18.43)

Grade

Low

25 (11.52)

High

192 (88.48)

T stage

Tis/Ta/T1

106 (48.85)

T2/T3/T4

111 (51.15)

Nodal status

N0/Nx

207 (95.39)

N1/N2

10 (4.61)

Initial metastasis

Yes

5 (2.3)

212 (97.7)

Multifocality

Yes

34 (15.67)

183 (84.33)

Size

< 3cm

97 (44.7)

≥ 3cm

120 (55.3)

Squamous differentiation

Yes

5 (2.3)

212 (97.7)

Free resection margin

Yes

208 (95.85)

9 (4.15)

Adjuvant therapy

Yes

44 (20.28)

173 (79.72)

CHOL

170 (144 - 193)

< 200

177 (81.57)

≥ 200

40 (18.43)

HDL

43.8 (35.7 - 56.4)

< 40 (men), < 50 (female)

107 (49.31)

≥ 40 (men), ≥ 50 (female)

110 (50.69)

LDL

93.6 (75.3 - 114)

< 130

185 (85.25)

≥ 130

32 (14.75)

103 (78 - 150)

< 150

162 (74.65)

≥ 150

55 (25.35)

**Table 2.** Oncologic Outcomes of UTUC Patients Receiving RNU
Variables	Number of patients (%)
UTUC: upper tract urothelial carcinoma; RNU: radical nephroureterectomy.
Total	217
Progression
Yes	51 (23.5%)
No	166 (76.5%)
Died of disease
Yes	16 (7.37%)
No	201 (92.63%)
All-caused death
Yes	41 (18.89%)
No	176 (81.11%)

Table 2. Oncologic Outcomes of UTUC Patients Receiving RNU

Variables

Number of patients (%)

UTUC: upper tract urothelial carcinoma; RNU: radical nephroureterectomy.

Total

217

Progression

Yes

51 (23.5%)

166 (76.5%)

Died of disease

Yes

16 (7.37%)

201 (92.63%)

All-caused death

Yes

41 (18.89%)

176 (81.11%)

**Table 3.** Univariate and Multivariate Standard Cox Regression Analysis
Variables	OS	PFS	CSS
Ref: reference; cHR: crude hazard ratio; aHR: adjusted hazard ratio; OS: overall survival; PFS: progression-free survival; CSS: cancer-specific survival: BMI: body mass index: CCI: Charlson Comorbidity Index; DM: diabetes mellitus
Age	1.052 (1.015 - 1.091)	0.0056	1.067 (1.012 - 1.124)	0.0158	1.018 (0.99 - 1.047)	0.2034	1.046 (1.01 - 1.084)	0.0112	1.051 (0.991 - 1.115)	0.0967	1.093 (0.984 - 1.215)	0.0968
Male (Ref: female)	2.728 (1.404 - 5.302)	0.0031	3.437 (1.476 - 8.001)	0.0042	2.316 (1.307 - 4.102)	0.004	2.727 (1.401 - 5.308)	0.0032	3.626 (1.144 - 11.489)	0.0286	5.893 (1.094 - 31.758)	0.039
BMI	0.959 (0.886 - 1.037)	0.2908	0.978 (0.89 - 1.074)	0.6429	0.937 (0.873 - 1.005)	0.0684	0.956 (0.885 - 1.033)	0.2529	0.914 (0.797 - 1.047)	0.1942	0.828 (0.648 - 1.058)	0.1311
CCI	1.18 (1.025 - 1.359)	0.0211	1.035 (0.848 - 1.264)	0.7344	0.996 (0.865 - 1.145)	0.9503	0.92 (0.765 - 1.105)	0.3699	1.221 (0.984 - 1.514)	0.0691	1.008 (0.724 - 1.404)	0.9616
Smoking (Ref: no)	2.121 (1.078 - 4.172)	0.0294	1.077 (0.416 - 2.79)	0.8792	1.583 (0.826 - 3.03)	0.166	0.685 (0.294 - 1.593)	0.3791	1.81 (0.576 - 5.69)	0.3098	1.703 (0.348 - 8.32)	0.5108
DM (Ref: no)	0.798 (0.411 - 1.55)	0.5054	0.835 (0.385 - 1.811)	0.6478	0.701 (0.383 - 1.282)	0.2488	1.087 (0.546 - 2.165)	0.8127	1.167 (0.411 - 3.314)	0.7713	1.819 (0.38 - 8.716)	0.4542
Hypertension (Ref: no)	1.675 (0.656 - 4.278)	0.2809	2.337 (0.841 - 6.496)	0.1037	0.489 (0.27 - 0.883)	0.0177	0.611 (0.313 - 1.194)	0.1495	-	-	-	-
High grade (Ref: low grade)	3.325 (0.799 - 13.833)	0.0985	2.304 (0.499 - 10.648)	0.2851	2.07 (0.743 - 5.764)	0.1639	0.954 (0.311 - 2.924)	0.9345	2.099 (0.274 - 16.081)	0.4756	1.344 (0.13 - 13.881)	0.8039
≥ pT2 stage (Ref: pTis/pTa/pT1)	2.872 (1.432 - 5.761)	0.003	2.473 (1.08 - 5.666)	0.0323	3.119 (1.682 - 5.784)	0.0003	2.455 (1.149 - 5.242)	0.0203	4.035 (1.135 - 14.344)	0.0311	4.426 (0.871 - 22.49)	0.0729
pN1/pN2 (Ref: pN0/pNx)	9.16 (4.094 - 20.498)	< 0.0001	2.612 (0.803 - 8.496)	0.1105	6.722 (2.954 - 15.297)	< 0.0001	1.461 (0.466 - 4.584)	0.5159	7.974 (2.182 - 29.138)	0.0017	1.779 (0.31 - 10.207)	0.5184
Metastasis (Ref: no)	4.951 (1.735 - 14.133)	0.0028	1.47 (0.402 - 5.37)	0.5603	6.005 (2.336 - 15.433)	0.0002	1.641 (0.495 - 5.434)	0.4179	9.822 (2.648 - 36.429)	0.0006	10.144 (1.558 - 66.038)	0.0154
Multifocality (Ref: no)	1.375 (0.653 - 2.899)	0.4022	1.468 (0.634 - 3.4)	0.3707	1.538 (0.803 - 2.946)	0.1941	2.384 (1.151 - 4.939)	0.0193	1.864 (0.584 - 5.953)	0.2931	4.388 (1.026 - 18.763)	0.046
Tumor size ≥ 3 cm (Ref: < 3 cm)	3.218 (1.567 - 6.606)	0.0015	2.945 (1.361 - 6.374)	0.0061	3.388 (1.768 - 6.49)	0.0002	3.022 (1.489 - 6.132)	0.0022	1.967 (0.668 - 5.793)	0.2195	0.771 (0.19 - 3.13)	0.7157
Squamous differentiation (Ref: no)	1.93 (0.263 - 14.191)	0.5181	0.765 (0.093 - 6.278)	0.8027	1.399 (0.192 - 10.209)	0.7408	0.734 (0.093 - 5.808)	0.7692	4.681 (0.605 - 36.2)	0.1391	1.784 (0.145 - 22.013)	0.6515
Positive margin (Ref: free)	4.445 (1.541 - 12.822)	0.0058	1.684 (0.415 - 6.824)	0.4657	7.535 (3.075 - 18.463)	< 0.0001	1.909 (0.573 - 6.361)	0.2925	8.211 (2.227 - 30.268)	0.0016	11.888 (1.488 - 94.97)	0.0195
Adjuvant therapy (Ref: no)	2.56 (1.325 - 4.944)	0.0051	1.236 (0.544 - 2.81)	0.6129	4.227 (2.403 - 7.435)	< 0.0001	2.857 (1.369 - 5.963)	0.0052	4.163 (1.455 - 11.916)	0.0078	1.68 (0.423 - 6.669)	0.4608

Table 3. Univariate and Multivariate Standard Cox Regression Analysis

Variables

PFS

CSS

Univariate

Multivariate

Univariate

Multivariate

Univariate

Multivariate

cHR

P value

aHR

P value

cHR

P value

aHR

P value

cHR

P value

aHR

P value

Ref: reference; cHR: crude hazard ratio; aHR: adjusted hazard ratio; OS: overall survival; PFS: progression-free survival; CSS: cancer-specific survival: BMI: body mass index: CCI: Charlson Comorbidity Index; DM: diabetes mellitus

Age

1.052 (1.015 - 1.091)

0.0056

1.067 (1.012 - 1.124)

0.0158

1.018 (0.99 - 1.047)

0.2034

1.046 (1.01 - 1.084)

0.0112

1.051 (0.991 - 1.115)

0.0967

1.093 (0.984 - 1.215)

0.0968

Male (Ref: female)

2.728 (1.404 - 5.302)

0.0031

3.437 (1.476 - 8.001)

0.0042

2.316 (1.307 - 4.102)

0.004

2.727 (1.401 - 5.308)

0.0032

3.626 (1.144 - 11.489)

0.0286

5.893 (1.094 - 31.758)

0.039

BMI

0.959 (0.886 - 1.037)

0.2908

0.978 (0.89 - 1.074)

0.6429

0.937 (0.873 - 1.005)

0.0684

0.956 (0.885 - 1.033)

0.2529

0.914 (0.797 - 1.047)

0.1942

0.828 (0.648 - 1.058)

0.1311

CCI

1.18 (1.025 - 1.359)

0.0211

1.035 (0.848 - 1.264)

0.7344

0.996 (0.865 - 1.145)

0.9503

0.92 (0.765 - 1.105)

0.3699

1.221 (0.984 - 1.514)

0.0691

1.008 (0.724 - 1.404)

0.9616

Smoking (Ref: no)

2.121 (1.078 - 4.172)

0.0294

1.077 (0.416 - 2.79)

0.8792

1.583 (0.826 - 3.03)

0.166

0.685 (0.294 - 1.593)

0.3791

1.81 (0.576 - 5.69)

0.3098

1.703 (0.348 - 8.32)

0.5108

DM (Ref: no)

0.798 (0.411 - 1.55)

0.5054

0.835 (0.385 - 1.811)

0.6478

0.701 (0.383 - 1.282)

0.2488

1.087 (0.546 - 2.165)

0.8127

1.167 (0.411 - 3.314)

0.7713

1.819 (0.38 - 8.716)

0.4542

Hypertension (Ref: no)

1.675 (0.656 - 4.278)

0.2809

2.337 (0.841 - 6.496)

0.1037

0.489 (0.27 - 0.883)

0.0177

0.611 (0.313 - 1.194)

0.1495

High grade (Ref: low grade)

3.325 (0.799 - 13.833)

0.0985

2.304 (0.499 - 10.648)

0.2851

2.07 (0.743 - 5.764)

0.1639

0.954 (0.311 - 2.924)

0.9345

2.099 (0.274 - 16.081)

0.4756

1.344 (0.13 - 13.881)

0.8039

≥ pT2 stage (Ref: pTis/pTa/pT1)

2.872 (1.432 - 5.761)

0.003

2.473 (1.08 - 5.666)

0.0323

3.119 (1.682 - 5.784)

0.0003

2.455 (1.149 - 5.242)

0.0203

4.035 (1.135 - 14.344)

0.0311

4.426 (0.871 - 22.49)

0.0729

pN1/pN2 (Ref: pN0/pNx)

9.16 (4.094 - 20.498)

< 0.0001

2.612 (0.803 - 8.496)

0.1105

6.722 (2.954 - 15.297)

< 0.0001

1.461 (0.466 - 4.584)

0.5159

7.974 (2.182 - 29.138)

0.0017

1.779 (0.31 - 10.207)

0.5184

Metastasis (Ref: no)

4.951 (1.735 - 14.133)

0.0028

1.47 (0.402 - 5.37)

0.5603

6.005 (2.336 - 15.433)

0.0002

1.641 (0.495 - 5.434)

0.4179

9.822 (2.648 - 36.429)

0.0006

10.144 (1.558 - 66.038)

0.0154

Multifocality (Ref: no)

1.375 (0.653 - 2.899)

0.4022

1.468 (0.634 - 3.4)

0.3707

1.538 (0.803 - 2.946)

0.1941

2.384 (1.151 - 4.939)

0.0193

1.864 (0.584 - 5.953)

0.2931

4.388 (1.026 - 18.763)

0.046

Tumor size ≥ 3 cm (Ref: < 3 cm)

3.218 (1.567 - 6.606)

0.0015

2.945 (1.361 - 6.374)

0.0061

3.388 (1.768 - 6.49)

0.0002

3.022 (1.489 - 6.132)

0.0022

1.967 (0.668 - 5.793)

0.2195

0.771 (0.19 - 3.13)

0.7157

Squamous differentiation (Ref: no)

1.93 (0.263 - 14.191)

0.5181

0.765 (0.093 - 6.278)

0.8027

1.399 (0.192 - 10.209)

0.7408

0.734 (0.093 - 5.808)

0.7692

4.681 (0.605 - 36.2)

0.1391

1.784 (0.145 - 22.013)

0.6515

Positive margin (Ref: free)

4.445 (1.541 - 12.822)

0.0058

1.684 (0.415 - 6.824)

0.4657

7.535 (3.075 - 18.463)

< 0.0001

1.909 (0.573 - 6.361)

0.2925

8.211 (2.227 - 30.268)

0.0016

11.888 (1.488 - 94.97)

0.0195

Adjuvant therapy (Ref: no)

2.56 (1.325 - 4.944)

0.0051

1.236 (0.544 - 2.81)

0.6129

4.227 (2.403 - 7.435)

< 0.0001

2.857 (1.369 - 5.963)

0.0052

4.163 (1.455 - 11.916)

0.0078

1.68 (0.423 - 6.669)

0.4608

**Table 4.** Univariate and Multivariate Standard Cox Regression Analysis of Lipid Profiles
Variables	OS	PFS	CSS
cHR: crude hazard ratio; aHR: adjusted hazard ratio; OS: overall survival; PFS: progression-free survival; CSS: cancer-specific survival; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.
CHOL	2.241 (1.169 - 4.294)	0.0151	2.652 (1.175 - 5.984)	0.0188	3.395 (1.938 - 5.948)	< 0.0001	2.916 (1.493 - 5.694)	0.0017	6.286 (2.235 - 17.682)	0.0005	9.97 (2.147 - 46.304)	0.0033
Low HDL	4.067 (1.797 - 9.208)	0.0008	5.925 (2.323 - 15.11)	0.0002	2.488 (1.343 - 4.609)	0.0038	4.238 (2.043 - 8.791)	0.0001	1.769 (0.603 - 5.19)	0.2991	1.447 (0.311 - 6.728)	0.6372
LDL	1.966 (0.96 - 4.025)	0.0645	1.788 (0.74 - 4.324)	0.1968	4.112 (2.326 - 7.27)	< 0.0001	3.492 (1.759 - 6.934)	0.0004	3.027 (1.033 - 8.87)	0.0435	1.754 (0.297 - 10.359)	0.5354
TG	2.689 (1.443 - 5.01)	0.0018	4.322 (2.057 - 9.08)	0.0001	2.05 (1.168 - 3.6)	0.0124	3.014 (1.604 - 5.663)	0.0006	3.594 (1.296 - 9.97)	0.014	6.342 (1.374 - 29.277)	0.0179

Table 4. Univariate and Multivariate Standard Cox Regression Analysis of Lipid Profiles

Variables

PFS

CSS

Univariate

Multivariate

Univariate

Multivariate

Univariate

Multivariate

cHR

P value

aHR

P value

cHR

P value

aHR

P value

cHR

P value

aHR

P value

cHR: crude hazard ratio; aHR: adjusted hazard ratio; OS: overall survival; PFS: progression-free survival; CSS: cancer-specific survival; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.

CHOL

2.241 (1.169 - 4.294)

0.0151

2.652 (1.175 - 5.984)

0.0188

3.395 (1.938 - 5.948)

< 0.0001

2.916 (1.493 - 5.694)

0.0017

6.286 (2.235 - 17.682)

0.0005

9.97 (2.147 - 46.304)

0.0033

Low HDL

4.067 (1.797 - 9.208)

0.0008

5.925 (2.323 - 15.11)

0.0002

2.488 (1.343 - 4.609)

0.0038

4.238 (2.043 - 8.791)

0.0001

1.769 (0.603 - 5.19)

0.2991

1.447 (0.311 - 6.728)

0.6372

LDL

1.966 (0.96 - 4.025)

0.0645

1.788 (0.74 - 4.324)

0.1968

4.112 (2.326 - 7.27)

< 0.0001

3.492 (1.759 - 6.934)

0.0004

3.027 (1.033 - 8.87)

0.0435

1.754 (0.297 - 10.359)

0.5354

2.689 (1.443 - 5.01)

0.0018

4.322 (2.057 - 9.08)

0.0001

2.05 (1.168 - 3.6)

0.0124

3.014 (1.604 - 5.663)

0.0006

3.594 (1.296 - 9.97)

0.014

6.342 (1.374 - 29.277)

0.0179

**Table 5.** Competing Risk Analysis of Lipid Profiles
Variables	PFS	CSS
cHR: crude hazard ratio; aHR: adjusted hazard ratio; PFS: progression-free survival; CSS: cancer-specific survival; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.
CHOL	2.657 (1.525 - 4.629)	0.0006	1.89 (0.82 - 4.36)	0.1353	4.815 (1.801 - 12.871)	0.0017	13.248 (1.612 - 108.882)	0.0162
Low HDL	1.384 (0.749 - 2.556)	0.2995	1.456 (0.702 - 3.018)	0.3126	0.849 (0.304 - 2.377)	0.756	0.478 (0.079 - 2.883)	0.4208
LDL	3.334 (1.831 - 6.071)	0.0001	2.479 (1.039 - 5.913)	0.0407	2.48 (0.847 - 7.258)	0.0974	1.67 (0.166 - 16.839)	0.6638
TG	1.423 (0.828 - 2.448)	0.2019	1.384 (0.72 - 2.659)	0.3298	2.155 (0.823 - 5.642)	0.1178	3.314 (0.968 - 11.352)	0.0564

Table 5. Competing Risk Analysis of Lipid Profiles

Variables

PFS

CSS

Univariate

Multivariate

Univariate

Multivariate

cHR

P value

aHR

P value

cHR

P value

aHR

P value

cHR: crude hazard ratio; aHR: adjusted hazard ratio; PFS: progression-free survival; CSS: cancer-specific survival; CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triacylglycerol.

CHOL

2.657 (1.525 - 4.629)

0.0006

1.89 (0.82 - 4.36)

0.1353

4.815 (1.801 - 12.871)

0.0017

13.248 (1.612 - 108.882)

0.0162

Low HDL

1.384 (0.749 - 2.556)

0.2995

1.456 (0.702 - 3.018)

0.3126

0.849 (0.304 - 2.377)

0.756

0.478 (0.079 - 2.883)

0.4208

LDL

3.334 (1.831 - 6.071)

0.0001

2.479 (1.039 - 5.913)

0.0407

2.48 (0.847 - 7.258)

0.0974

1.67 (0.166 - 16.839)

0.6638

1.423 (0.828 - 2.448)

0.2019

1.384 (0.72 - 2.659)

0.3298

2.155 (0.823 - 5.642)

0.1178

3.314 (0.968 - 11.352)

0.0564