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 000, Number 000, October 2024, pages 000-000

The Association of Preoperative Prognostic Nutritional Index With Survival Outcome in Ovarian Clear Cell Cancer

Figure 1. Kaplan-Meier curves of (a) overall survival and (b) progression-free survival of epithelial ovarian clear cell cancer patients stratified by preoperative prognostic nutritional index (PPNI).

Figure 2. Kaplan-Meier curves of (a) overall survival and (b) progression-free survival of epithelial ovarian clear cell cancer patients stratified by preoperative prognostic nutritional index (PPNI) after adjusting for body mass index (BMI), cancer antigen 125 (CA125) level, albumin level, lymphocyte count, hemoglobin level, platelet count, stage of cancer, optimal surgery, and ascites cytology.

**Table 1.** Baseline Clinical Characteristics of Patients With EOC-CC Stratified by PPNI
Variables	Total (n = 290)	Low PPNI group (n = 115)	High PPNI group (n = 175)	P-value
Low PPNI is defined as PPNI level less than 50; high PPNI is defined as PPNI level greater than or equal to 50. *Statistically significance (P < 0.05). BMI: body mass index; CA125: cancer antigen 125; EOC-CC: epithelial ovarian clear cell cancer; FIGO: International Federation of Gynecology and Obstetrics; PPNI: preoperative prognostic nutritional index; SD: standard deviation; WBC: white blood cell.
Age (years), mean ± SD	53.3 ± 9.4	53.7 ± 9.9	53.0 ± 9.0	0.552
Menopausal status, n (%)				0.811
Pre-menopause	101 (34.8)	41 (35.6)	60 (34.3)
Post-menopause	189 (65.2)	74 (64.4)	115 (65.7)
BMI, n (%)				0.042*
< 25 kg/m²	189 (65.2)	83 (72.2)	106 (60.6)
≥ 25 kg/m²	101 (34.8)	32 (27.8)	69 (39.4)
Presence of underlying disease, n (%)	53 (18.3)	23 (20.0)	30 (17.1)	0.538
Presence of diabetic mellitus, n (%)	18 (6.2)	8 (7.0)	10 (5.7)	0.668
Presence of hypertension, n (%)	39 (13.4)	17 (14.8)	22 (12.6)	0.589
CA125, n (%)				0.003*
< 35 U/mL	72 (24.8)	18 (15.6)	54 (30.9)
≥ 35 U/mL	218 (75.2)	97 (84.4)	121 (69.1)
Albumin (g/dL), mean ± SD	4.1 ± 0.5	3.6 ± 0.6	4.4 ± 2.8	< 0.001*
WBC (cells/mm³), median (min. - max.)	7,635 (3,000 - 16,500)	7,700 (2,300 - 17,400)	7,500 (3,700 - 15,200)	0.452
Lymphocyte (%), median (min. - max.)	26.7 (3.9 - 65.0)	19.0 (3.5 - 72.0)	30.6 (12.7 - 63.7)	< 0.001*
Hemoglobin (g/dL), mean ± SD	11.1 ± 1.4	10.7 ± 1.5	11.4 ± 1.4	< 0.001*
Platelet count (× 10³ cells/mm³), mean ± SD	358.0 ± 138.9	395.2 ± 163.5	333.6 ± 114.2	< 0.001*
FIGO 2014 staging, n (%)				< 0.001*
Early stage (I-II)	222 (76.6)	73 (63.5)	149 (85.1)
Advance stage (III-IV)	68 (23.4)	42 (36.5)	26 (14.9)
Surgery, n (%)				0.013*
Incomplete surgical staging	64 (22.1)	34 (29.6)	30 (17.1)
Complete surgical staging	226 (77.9)	81 (70.4)	145 (82.9)
Optimal surgery, n (%)				< 0.001*
No	28 (9.7)	21 (18.3)	7 (4.0)
Yes	262 (90.3)	94 (81.7)	168 (96.0)
Residual disease, n (%)				< 0.001*
No	262 (90.3)	92 (80.0)	170 (97.1)
Yes	28 (9.7)	23 (20.0)	5 (2.9)
Ascites cytology, n (%)				< 0.001*
Negative	224 (77.2)	73 (63.5)	151 (86.3)
Positive	66 (22.8)	42 (36.5)	24 (13.7)
Adjuvant chemotherapy, n (%)				0.650
No	4 (1.4)	2 (1.7)	2 (1.1)
Paclitaxel + carboplatin	286 (98.6)	113 (98.3)	173 (98.9)
Cycles of chemotherapy, n (%)				0.096
≤ 3	17 (5.9)	10 (8.7)	7 (4.0)
> 3	273 (94.1)	105 (91.3)	168 (96.0)

Table 1. Baseline Clinical Characteristics of Patients With EOC-CC Stratified by PPNI

Variables

Total (n = 290)

Low PPNI group (n = 115)

High PPNI group (n = 175)

P-value

Low PPNI is defined as PPNI level less than 50; high PPNI is defined as PPNI level greater than or equal to 50. *Statistically significance (P < 0.05). BMI: body mass index; CA125: cancer antigen 125; EOC-CC: epithelial ovarian clear cell cancer; FIGO: International Federation of Gynecology and Obstetrics; PPNI: preoperative prognostic nutritional index; SD: standard deviation; WBC: white blood cell.

Age (years), mean ± SD

53.3 ± 9.4

53.7 ± 9.9

53.0 ± 9.0

0.552

Menopausal status, n (%)

0.811

Pre-menopause

101 (34.8)

41 (35.6)

60 (34.3)

Post-menopause

189 (65.2)

74 (64.4)

115 (65.7)

BMI, n (%)

0.042*

< 25 kg/m²

189 (65.2)

83 (72.2)

106 (60.6)

≥ 25 kg/m²

101 (34.8)

32 (27.8)

69 (39.4)

Presence of underlying disease, n (%)

53 (18.3)

23 (20.0)

30 (17.1)

0.538

Presence of diabetic mellitus, n (%)

18 (6.2)

8 (7.0)

10 (5.7)

0.668

Presence of hypertension, n (%)

39 (13.4)

17 (14.8)

22 (12.6)

0.589

CA125, n (%)

0.003*

< 35 U/mL

72 (24.8)

18 (15.6)

54 (30.9)

≥ 35 U/mL

218 (75.2)

97 (84.4)

121 (69.1)

Albumin (g/dL), mean ± SD

4.1 ± 0.5

3.6 ± 0.6

4.4 ± 2.8

< 0.001*

WBC (cells/mm³), median (min. - max.)

7,635 (3,000 - 16,500)

7,700 (2,300 - 17,400)

7,500 (3,700 - 15,200)

0.452

Lymphocyte (%), median (min. - max.)

26.7 (3.9 - 65.0)

19.0 (3.5 - 72.0)

30.6 (12.7 - 63.7)

< 0.001*

Hemoglobin (g/dL), mean ± SD

11.1 ± 1.4

10.7 ± 1.5

11.4 ± 1.4

< 0.001*

Platelet count (× 10³ cells/mm³), mean ± SD

358.0 ± 138.9

395.2 ± 163.5

333.6 ± 114.2

< 0.001*

FIGO 2014 staging, n (%)

< 0.001*

Early stage (I-II)

222 (76.6)

73 (63.5)

149 (85.1)

Advance stage (III-IV)

68 (23.4)

42 (36.5)

26 (14.9)

Surgery, n (%)

0.013*

Incomplete surgical staging

64 (22.1)

34 (29.6)

30 (17.1)

Complete surgical staging

226 (77.9)

81 (70.4)

145 (82.9)

Optimal surgery, n (%)

< 0.001*

28 (9.7)

21 (18.3)

7 (4.0)

Yes

262 (90.3)

94 (81.7)

168 (96.0)

Residual disease, n (%)

< 0.001*

262 (90.3)

92 (80.0)

170 (97.1)

Yes

28 (9.7)

23 (20.0)

5 (2.9)

Ascites cytology, n (%)

< 0.001*

Negative

224 (77.2)

73 (63.5)

151 (86.3)

Positive

66 (22.8)

42 (36.5)

24 (13.7)

Adjuvant chemotherapy, n (%)

0.650

4 (1.4)

2 (1.7)

2 (1.1)

Paclitaxel + carboplatin

286 (98.6)

113 (98.3)

173 (98.9)

Cycles of chemotherapy, n (%)

0.096

≤ 3

17 (5.9)

10 (8.7)

7 (4.0)

> 3

273 (94.1)

105 (91.3)

168 (96.0)

**Table 2.** Patterns of Recurrence and Death Stratified by PPNI in Patients With EOC-CC
Variables	Total (n = 290)	Low PPNI group (n = 115)	High PPNI group (n = 175)	P-value
Low PPNI is defined as PPNI level less than 50; high PPNI is defined as PPNI level greater than or equal to 50. *Statistically significance (P < 0.05). EOC-CC: epithelial ovarian clear cell cancer; PPNI: preoperative prognostic nutritional index.
Recurrence, n (%)				0.041*
No	187 (64.5)	66 (57.4)	121 (69.1)
Yes	103 (35.5)	49 (42.6)	54 (30.9)
Site of recurrence, n (%)				0.089
Locoregional	70 (68.0)	38 (76.0)	32 (60.4)
Distant	33 (32.0)	12 (24.0)	21 (39.6)
Death, n (%)				0.001*
No	181 (62.4)	58 (50.4)	123 (70.3)
Yes	109 (37.6)	57 (49.6)	52 (29.7)
Cause of death, n (%)				0.192
Non-cancer	31 (28.4)	12 (22.6)	19 (33.9)
Cancer	78 (71.6)	41 (77.4)	37 (66.1)

Table 2. Patterns of Recurrence and Death Stratified by PPNI in Patients With EOC-CC

Variables

Total (n = 290)

Low PPNI group (n = 115)

High PPNI group (n = 175)

P-value

Low PPNI is defined as PPNI level less than 50; high PPNI is defined as PPNI level greater than or equal to 50. *Statistically significance (P < 0.05). EOC-CC: epithelial ovarian clear cell cancer; PPNI: preoperative prognostic nutritional index.

Recurrence, n (%)

0.041*

187 (64.5)

66 (57.4)

121 (69.1)

Yes

103 (35.5)

49 (42.6)

54 (30.9)

Site of recurrence, n (%)

0.089

Locoregional

70 (68.0)

38 (76.0)

32 (60.4)

Distant

33 (32.0)

12 (24.0)

21 (39.6)

Death, n (%)

0.001*

181 (62.4)

58 (50.4)

123 (70.3)

Yes

109 (37.6)

57 (49.6)

52 (29.7)

Cause of death, n (%)

0.192

Non-cancer

31 (28.4)

12 (22.6)

19 (33.9)

Cancer

78 (71.6)

41 (77.4)

37 (66.1)

**Table 3.** Five-Year Survival Rates of Patients With EOC-CC Stratified by PPNI
Survival rates	Total patients	Low PPNI group	High PPNI group
*Adjusted for BMI, CA125, albumin, lymphocyte, hemoglobin, platelet, stage of cancer, optimal surgery, and ascites cytology. CI: confidence interval; EOC-CC: epithelial ovarian clear cell cancer; OS: overall survival; PFS: progression-free survival; PPNI: preoperative prognostic nutritional index.
5-year OS	68.6 (62.8 - 73.7)	56.8 (46.9 - 65.5)	76.4 (69.2 - 82.2)
5-year PFS	66.1 (60.3 - 71.3)	58.7 (49.1 - 67.1)	71.0 (63.5 - 77.2)
After adjusted for confounding factors*
5-year OS	90.9	93.3	70.0
5-year PFS	94.9	93.6	94.0

Table 3. Five-Year Survival Rates of Patients With EOC-CC Stratified by PPNI

Survival rates

Total patients

Low PPNI group

High PPNI group

% (95% CI)

*Adjusted for BMI, CA125, albumin, lymphocyte, hemoglobin, platelet, stage of cancer, optimal surgery, and ascites cytology. CI: confidence interval; EOC-CC: epithelial ovarian clear cell cancer; OS: overall survival; PFS: progression-free survival; PPNI: preoperative prognostic nutritional index.

5-year OS

68.6 (62.8 - 73.7)

56.8 (46.9 - 65.5)

76.4 (69.2 - 82.2)

5-year PFS

66.1 (60.3 - 71.3)

58.7 (49.1 - 67.1)

71.0 (63.5 - 77.2)

After adjusted for confounding factors*

5-year OS

90.9

93.3

70.0

5-year PFS

94.9

93.6

94.0

**Table 4.** Univariate and Multivariate Analyses for Survival Outcomes According to Individual Parameters
Parameters	PFS	OS
*Statistically significance (95% CI does not include 1). BMI: body mass index; CA125: cancer antigen 125; CI: confidence interval; FIGO: International Federation of Gynecology and Obstetrics; HR: hazard ratio; OS: overall survival; PFS: progression-free survival; PPNI: preoperative prognostic nutritional index.
Univariate analysis
PPNI (< 50 vs. ≥ 50)	0.63 (0.43 - 0.92)*	0.018	0.51 (0.35 - 0.75)*	0.001
Menopause (pre- vs. post-menopause)	1.14 (0.75 - 1.72)	0.543	1.20 (0.80 - 1.80)	0.384
BMI (≤ 25 kg/m² vs. > 25 kg/m²)	0.60 (0.39 - 0.93)*	0.022	0.73 (0.48 - 1.10)	0.129
Underlying disease (no vs. yes)	1.04 (0.63 - 1.71)*	0.077	1.11 (0.68 - 1.81)	0.673
CA125 level (< 35 vs. ≥ 35 U/mL)	1.99 (1.18 - 3.36)*	0.009	2.46 (1.45 - 4.20)*	0.001
Albumin (< 3.5 g/dL vs. ≥ 3.5 g/dL)	0.51 (0.31 - 0.84)*	<0.001	0.39 (0.25 - 0.62)*	< 0.001
Lymphocyte (< 30% vs. ≥ 30%)	0.60 (0.40 - 0.91)*	0.015	0.54 (0.36 - 0.82)*	0.003
Hemoglobin (< 10 g/dL vs. ≥ 10 g/dL)	0.57 (0.37 - 0.87)*	0.009	0.54 (0.36 - 0.82)*	0.004
Platelet count (< 350 vs. ≥ 350 × 10³ cells/mm³)	1.69 (1.15 - 2.49)*	0.008	1.89 (1.30 - 2.76)*	0.001
FIGO 2014 stage (I-II vs. III-IV)	7.60 (5.11 - 11.30)*	<0.001	6.78 (4.59 - 10.02)*	< 0.001
Optimal surgery (no vs. yes)	0.22 (0.14 - 0.35)*	<0.001	0.17 (0.11 - 0.27)*	< 0.001
Ascites cytology (negative vs. positive)	2.75 (1.84 - 4.10)*	<0.001	3.21 (2.18 - 4.73)*	< 0.001
Cycles of chemotherapy (≤ 3 vs. > 3)	1.45 (0.53 - 3.94)	0.465	0.49 (0.24 - 1.00)	0.052
Multivariate analysis
PPNI (< 50 vs. ≥ 50)	1.14 (0.70 - 1.86)	0.590	0.89 (0.56 - 1.41)	0.608
BMI (≤ 25 kg/m² vs. > 25 kg/m²)	0.68 (0.42 - 1.11)	0.125	-	-
Underlying disease (no vs. yes)	0.92 (0.53 - 1.62)	0.783	-	-
CA125 level (< 35 vs. ≥ 35 U/mL)	1.61 (0.94 - 2.76)	0.082	2.09 (1.21 - 3.62)*	0.009
Albumin (< 3.5 g/dL vs. ≥ 3.5 g/dL)	1.47 (0.78 - 2.78)	0.235	1.02 (0.57 - 1.84)	0.932
Lymphocyte (< 30% vs. ≥ 30%)	0.81 (0.50 - 1.31)	0.395	0.78 (0.49 - 1.26)	0.315
Hemoglobin (< 10 g/dL vs. ≥ 10 g/dL)	0.95 (0.59 - 1.54)	0.836	0.76 (0.49 - 1.20)	0.247
Platelet count (< 350 vs. ≥ 350) × 10³ cells/mm³	1.08 (0.69 - 1.68)	0.731	1.13 (0.72 - 1.76)	0.594
FIGO 2014 stage (I-II vs. III-IV)	7.30 (4.38 - 12.17)*	<0.001	4.69 (2.79 - 7.89)*	< 0.001
Optimal surgery (no vs. yes)	0.71 (0.39 - 1.30)	0.269	0.57 (0.32 - 1.01)	0.054
Ascites cytology (negative vs. positive)	0.91 (0.52 - 1.58)	0.733	1.08 (0.63 - 1.85)	0.770
Cycles of chemotherapy (≤ 3 vs. > 3)	-	-	0.31 (0.15 - 0.65)*	0.002

Table 4. Univariate and Multivariate Analyses for Survival Outcomes According to Individual Parameters

Parameters

PFS

HR (95% CI)

P-value

HR (95% CI)

P-value

*Statistically significance (95% CI does not include 1). BMI: body mass index; CA125: cancer antigen 125; CI: confidence interval; FIGO: International Federation of Gynecology and Obstetrics; HR: hazard ratio; OS: overall survival; PFS: progression-free survival; PPNI: preoperative prognostic nutritional index.

Univariate analysis

PPNI (< 50 vs. ≥ 50)

0.63 (0.43 - 0.92)*

0.018

0.51 (0.35 - 0.75)*

0.001

Menopause (pre- vs. post-menopause)

1.14 (0.75 - 1.72)

0.543

1.20 (0.80 - 1.80)

0.384

BMI (≤ 25 kg/m² vs. > 25 kg/m²)

0.60 (0.39 - 0.93)*

0.022

0.73 (0.48 - 1.10)

0.129

Underlying disease (no vs. yes)

1.04 (0.63 - 1.71)*

0.077

1.11 (0.68 - 1.81)

0.673

CA125 level (< 35 vs. ≥ 35 U/mL)

1.99 (1.18 - 3.36)*

0.009

2.46 (1.45 - 4.20)*

0.001

Albumin (< 3.5 g/dL vs. ≥ 3.5 g/dL)

0.51 (0.31 - 0.84)*

<0.001

0.39 (0.25 - 0.62)*

< 0.001

Lymphocyte (< 30% vs. ≥ 30%)

0.60 (0.40 - 0.91)*

0.015

0.54 (0.36 - 0.82)*

0.003

Hemoglobin (< 10 g/dL vs. ≥ 10 g/dL)

0.57 (0.37 - 0.87)*

0.009

0.54 (0.36 - 0.82)*

0.004

Platelet count (< 350 vs. ≥ 350 × 10³ cells/mm³)

1.69 (1.15 - 2.49)*

0.008

1.89 (1.30 - 2.76)*

0.001

FIGO 2014 stage (I-II vs. III-IV)

7.60 (5.11 - 11.30)*

<0.001

6.78 (4.59 - 10.02)*

< 0.001

Optimal surgery (no vs. yes)

0.22 (0.14 - 0.35)*

<0.001

0.17 (0.11 - 0.27)*

< 0.001

Ascites cytology (negative vs. positive)

2.75 (1.84 - 4.10)*

<0.001

3.21 (2.18 - 4.73)*

< 0.001

Cycles of chemotherapy (≤ 3 vs. > 3)

1.45 (0.53 - 3.94)

0.465

0.49 (0.24 - 1.00)

0.052

Multivariate analysis

PPNI (< 50 vs. ≥ 50)

1.14 (0.70 - 1.86)

0.590

0.89 (0.56 - 1.41)

0.608

BMI (≤ 25 kg/m² vs. > 25 kg/m²)

0.68 (0.42 - 1.11)

0.125

Underlying disease (no vs. yes)

0.92 (0.53 - 1.62)

0.783

CA125 level (< 35 vs. ≥ 35 U/mL)

1.61 (0.94 - 2.76)

0.082

2.09 (1.21 - 3.62)*

0.009

Albumin (< 3.5 g/dL vs. ≥ 3.5 g/dL)

1.47 (0.78 - 2.78)

0.235

1.02 (0.57 - 1.84)

0.932

Lymphocyte (< 30% vs. ≥ 30%)

0.81 (0.50 - 1.31)

0.395

0.78 (0.49 - 1.26)

0.315

Hemoglobin (< 10 g/dL vs. ≥ 10 g/dL)

0.95 (0.59 - 1.54)

0.836

0.76 (0.49 - 1.20)

0.247

Platelet count (< 350 vs. ≥ 350) × 10³ cells/mm³

1.08 (0.69 - 1.68)

0.731

1.13 (0.72 - 1.76)

0.594

FIGO 2014 stage (I-II vs. III-IV)

7.30 (4.38 - 12.17)*

<0.001

4.69 (2.79 - 7.89)*

< 0.001

Optimal surgery (no vs. yes)

0.71 (0.39 - 1.30)

0.269

0.57 (0.32 - 1.01)

0.054

Ascites cytology (negative vs. positive)

0.91 (0.52 - 1.58)

0.733

1.08 (0.63 - 1.85)

0.770

Cycles of chemotherapy (≤ 3 vs. > 3)

0.31 (0.15 - 0.65)*

0.002