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 http://www.wjon.org

Original Article

Volume 10, Number 6, December 2019, pages 218-225

Combining Prostate-Specific Antigen Parameters With Prostate Imaging Reporting and Data System Score Version 2.0 to Improve Its Diagnostic Accuracy

Figure 1. ROC curve analysis of PIRADS score criteria to determine CSPCa. ROC: receiver operating characteristic; PIRADS: Prostate Imaging Reporting and Data System; CSPCa: clinically significant prostate cancer.

**Table 1.** Demographic Characteristics of Patients With Suspected PCa, Patients With PCa and Patients With BPH
Characteristics	Patients with suspected PCa (n = 104)	Patients with PCa (n = 64)	Patients with BPH (n = 40)	P value*
Data shown as median (interquartile range), range. Unless otherwise specified. *Comparison between patients with PCa and patients with BPH. BPH: benign prostatic hyperplasia; DRE: digital rectal examination; PCa: prostate cancer; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.
Age (years)	68 (60.25 - 71) 45 - 85	68 (62 - 71)	65.5 (54.25 - 70)	0.009
PSA level (ng/mL)	8.15 (6.4 - 9.7) 4.1 - 10	9.05 (7.73 - 9.9)	6.4 (5.5 - 7.8)	< 0.001
Prostate volume (mL)	60 (44 - 75) 27 - 123	50 (43.25 - 60.75)	75 (56.75 - 94)	< 0.001
PSAD (ng/mL²)	0.13 (0.09 - 0.18) 0.05 - 0.27	0.16 (0.13 - 0.21)	0.09 (0.08 - 0.11)	< 0.001
Free/total PSA ratio (%)	21.5 (14.52 - 29.92) 5.5 - 44	16.75 (12.58-23)	30 (23.75 - 35)	< 0.001
Suspicious DRE, n (%)	17 (16.3)	12 (18.8)	5 (12.5)	0.402
Hypoechoic lesion in TRUS/USG, n (%)	5 (4.8)	5 (7.8)	0 (0)	0.070

Table 1. Demographic Characteristics of Patients With Suspected PCa, Patients With PCa and Patients With BPH

Characteristics

Patients with suspected PCa (n = 104)

Patients with PCa (n = 64)

Patients with BPH (n = 40)

P value*

Data shown as median (interquartile range), range. Unless otherwise specified. *Comparison between patients with PCa and patients with BPH. BPH: benign prostatic hyperplasia; DRE: digital rectal examination; PCa: prostate cancer; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.

Age (years)

68 (60.25 - 71)
45 - 85

68 (62 - 71)

65.5 (54.25 - 70)

0.009

PSA level (ng/mL)

8.15 (6.4 - 9.7)
4.1 - 10

9.05 (7.73 - 9.9)

6.4 (5.5 - 7.8)

< 0.001

Prostate volume (mL)

60 (44 - 75)
27 - 123

50 (43.25 - 60.75)

75 (56.75 - 94)

< 0.001

PSAD (ng/mL²)

0.13 (0.09 - 0.18)
0.05 - 0.27

0.16 (0.13 - 0.21)

0.09 (0.08 - 0.11)

< 0.001

Free/total PSA ratio (%)

21.5 (14.52 - 29.92)
5.5 - 44

16.75 (12.58-23)

30 (23.75 - 35)

< 0.001

Suspicious DRE, n (%)

17 (16.3)

12 (18.8)

5 (12.5)

0.402

Hypoechoic lesion in TRUS/USG, n (%)

5 (4.8)

5 (7.8)

0 (0)

0.070

**Table 2.** Comparison of Demographic Data Between Patients in CSPCa Group and Patients in Non-CSPCa Group (Having Insignificant Cancer or BPH)
Variables	CSPCa group (n = 44)	Non-CSPCa group (n = 60)	P value
Data shown as median (interquartile range), range. Unless otherwise specified. CSPCa: clinically significant PCa; BPH: benign prostatic hyperplasia; DRE: digital rectal examination; PCa: prostatic cancer; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.
Age (years)	70 (63.25 - 73.75)	66 (59 - 70)	0.001
PSA level (ng/mL)	9.6 (8.43 - 10)	6.95 (5.5 - 8.4)	< 0.001
Prostate volume (mL)	44.5 (40.25 - 59.15)	70 (56 - 89.75)	< 0.001
PSAD (ng/mL²)	0.20 (0.16 - 0.22)	0.10 (0.08 - 0.12)	< 0.001
Free/total PSA ratio (%)	14.25 (11.08 - 18.73)	28 (21.25 - 33)	< 0.001
DRE positive, n (%)	7 (15.9)	10 (16.7)	0.918
USG/TRUS positive, n (%)	4 (9.1)	1 (1.7)	0.080

Table 2. Comparison of Demographic Data Between Patients in CSPCa Group and Patients in Non-CSPCa Group (Having Insignificant Cancer or BPH)

Variables

CSPCa group (n = 44)

Non-CSPCa group (n = 60)

P value

Data shown as median (interquartile range), range. Unless otherwise specified. CSPCa: clinically significant PCa; BPH: benign prostatic hyperplasia; DRE: digital rectal examination; PCa: prostatic cancer; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.

Age (years)

70 (63.25 - 73.75)

66 (59 - 70)

0.001

PSA level (ng/mL)

9.6 (8.43 - 10)

6.95 (5.5 - 8.4)

< 0.001

Prostate volume (mL)

44.5 (40.25 - 59.15)

70 (56 - 89.75)

< 0.001

PSAD (ng/mL²)

0.20 (0.16 - 0.22)

0.10 (0.08 - 0.12)

< 0.001

Free/total PSA ratio (%)

14.25 (11.08 - 18.73)

28 (21.25 - 33)

< 0.001

DRE positive, n (%)

7 (15.9)

10 (16.7)

0.918

USG/TRUS positive, n (%)

4 (9.1)

1 (1.7)

0.080

**Table 3.** Comparison of PIRADS Score Between Patients in CSPCa Group and Patients in Non-CSPCa Group (Having Insignificant Cancer or BPH)
Multiparametric MRI results	CSPCa group (n = 44)	Non-CSPCa group (n = 60)	P value
Data shown as n (%). *PIRADS score 3, 4 or 5 is considered as a positive test. CSPCa: clinically significant prostate cancer; BPH: benign prostatic hyperplasia; PIRAD: Prostate Imaging Reporting and Data System; MRI: magnetic resonance imaging.
PIRADS (+)*	38 (86.4)	32 (53.3)	< 0.001
PIRADS score 1	2 (4.5)	7 (11.7)	< 0.001
PIRADS score 2	3 (6.8)	21 (35)
PIRADS score 3	6 (13.6)	22 (36.7)
PIRADS score 4	11 (25)	7 (11.7)
PIRADS score 5	22 (50)	3 (5)

Table 3. Comparison of PIRADS Score Between Patients in CSPCa Group and Patients in Non-CSPCa Group (Having Insignificant Cancer or BPH)

Multiparametric MRI results

CSPCa group (n = 44)

Non-CSPCa group (n = 60)

P value

Data shown as n (%). *PIRADS score 3, 4 or 5 is considered as a positive test. CSPCa: clinically significant prostate cancer; BPH: benign prostatic hyperplasia; PIRAD: Prostate Imaging Reporting and Data System; MRI: magnetic resonance imaging.

PIRADS (+)*

38 (86.4)

32 (53.3)

< 0.001

PIRADS score 1

2 (4.5)

7 (11.7)

< 0.001

PIRADS score 2

3 (6.8)

21 (35)

PIRADS score 3

6 (13.6)

22 (36.7)

PIRADS score 4

11 (25)

7 (11.7)

PIRADS score 5

22 (50)

3 (5)

**Table 4.** ROC Curve Analysis for Predicting Clinically Significant PCa for Each Factor
Parameters	AUC of ROC curve	95% confidence interval	P value
AUC: area under the ROC curve; PCa: prostatic cancer; DRE: digital rectal examination; PIRADS: Prostate Imaging Reporting and Data System; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; ROC: receiver operating characteristic; TRUS: transrectal ultrasound; USG: ultrasound sonography.
Age	0.684	0.582 - 0.785	0.001
DRE	0.496	0.383 - 0.609	0.948
USG/TRUS	0.537	0.423 - 0.651	0.519
Serum PSA	0.827	0.744 - 0.909	< 0.001
Prostate volume	0.830	0.753 - 0.907	< 0.001
PSAD	0.968	0.941 - 0.996	< 0.001
Free/total PSA ratio (%)	0.855	0.776 - 0.935	< 0.001
PIRADS score V2	0.822	0.734 - 0.909	< 0.001

Table 4. ROC Curve Analysis for Predicting Clinically Significant PCa for Each Factor

Parameters

AUC of ROC curve

95% confidence interval

P value

AUC: area under the ROC curve; PCa: prostatic cancer; DRE: digital rectal examination; PIRADS: Prostate Imaging Reporting and Data System; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; ROC: receiver operating characteristic; TRUS: transrectal ultrasound; USG: ultrasound sonography.

Age

0.684

0.582 - 0.785

0.001

DRE

0.496

0.383 - 0.609

0.948

USG/TRUS

0.537

0.423 - 0.651

0.519

Serum PSA

0.827

0.744 - 0.909

< 0.001

Prostate volume

0.830

0.753 - 0.907

< 0.001

PSAD

0.968

0.941 - 0.996

< 0.001

Free/total PSA ratio (%)

0.855

0.776 - 0.935

< 0.001

PIRADS score V2

0.822

0.734 - 0.909

< 0.001

**Table 5.** Univariate and Multivariate Logistic Regression Analysis of Factors Associated With Clinically Significant PCa in Patients With Suspected PCa
Parameters	Odds ratio (95% CI)	P value
PCa: prostatic cancer; DRE: digital rectal examination; PIRADS: Prostate Imaging Reporting and Data System; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.
Age
Univariate	1.101 (1.038 - 1.67)	0.001
Multivariate	1.157 (1.008 - 1.327)	0.038
DRE (+)	0.946 (0.329 - 2.717)	0.918
TRUS/USG (+)	0.169 (0.018 - 1.573)	0.118
Prostate volume	0.916 (0.882 - 0.950)	< 0.001
Serum PSA
Univariate	1.929 (1.442 - 2.580)	< 0.001
Multivariate	0.930 (0.571 - 1.515)	0.772
PSAD
Univariate	2.090 (1.559 - 2.802)	< 0.001
Multivariate	2.033 (1.466 - 2.819)	< 0.001
Free/total PSA ratio (%)
Univariate	0.843 (0.787 - 0.902)	< 0.001
Multivariate	0.939 (0.846 - 1.043)	0.243
PIRADS V2	5.542 (2.04 - 15.053)	0.001

Table 5. Univariate and Multivariate Logistic Regression Analysis of Factors Associated With Clinically Significant PCa in Patients With Suspected PCa

Parameters

Odds ratio (95% CI)

P value

PCa: prostatic cancer; DRE: digital rectal examination; PIRADS: Prostate Imaging Reporting and Data System; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density; TRUS: transrectal ultrasound; USG: ultrasound sonography.

Age

Univariate

1.101 (1.038 - 1.67)

0.001

Multivariate

1.157 (1.008 - 1.327)

0.038

DRE (+)

0.946 (0.329 - 2.717)

0.918

TRUS/USG (+)

0.169 (0.018 - 1.573)

0.118

Prostate volume

0.916 (0.882 - 0.950)

< 0.001

Serum PSA

Univariate

1.929 (1.442 - 2.580)

< 0.001

Multivariate

0.930 (0.571 - 1.515)

0.772

PSAD

Univariate

2.090 (1.559 - 2.802)

< 0.001

Multivariate

2.033 (1.466 - 2.819)

< 0.001

Free/total PSA ratio (%)

Univariate

0.843 (0.787 - 0.902)

< 0.001

Multivariate

0.939 (0.846 - 1.043)

0.243

PIRADS V2

5.542 (2.04 - 15.053)

0.001

**Table 6.** PIRADS Score Criteria Used in the Study
Criteria	Postive test	Negative test	Remarks
PIRADS: Prostate Imaging Reporting and Data System; fPSA: free/total PSA ratio; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density.
1	Score 3,4 or 5	Score 1 or 2	Standard
2	Score 4, 5 or (3+ PSAD > 0.12 ng/mL²)	Score 1, 2 or (3+ PSAD ≤ 0.12 ng/mL² )	Combining present study cut-off of PSAD with score 3
3	Score 4, 5 or (3+ fPSA ≤ 25.5%)	Score 1, 2 or (3+ fPSA > 25.5%)	Combining present study cut-off of fPSA with score 3
4	Score 4 or 5	Score 1, 2 or 3	Score 3 taken as a negative test due to high rate of false positive in this study when score 3 is taken as positive.

Table 6. PIRADS Score Criteria Used in the Study

Criteria

Postive test

Negative test

Remarks

PIRADS: Prostate Imaging Reporting and Data System; fPSA: free/total PSA ratio; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density.

Score 3,4 or 5

Score 1 or 2

Standard

Score 4, 5 or (3+ PSAD > 0.12 ng/mL²)

Score 1, 2 or (3+ PSAD ≤ 0.12 ng/mL² )

Combining present study cut-off of PSAD with score 3

Score 4, 5 or (3+ fPSA ≤ 25.5%)

Score 1, 2 or (3+ fPSA > 25.5%)

Combining present study cut-off of fPSA with score 3

Score 4 or 5

Score 1, 2 or 3

Score 3 taken as a negative test due to high rate of false positive in this study when score 3 is taken as positive.

**Table 7.** Diagnostic Evaluation of PIRADS Score in Predicting CSPCa in Patients With Suspected PCa Using Criterion 1, Criterion 2 and Criterion 3
Clinical group	Clinically significant PCa with PIRADS scoring
Data shown as percentage (95% CI). CI: confidence interval; fPSA: free/total prostate specific antigen ratio; PCa: prostate cancer; PIRADS: Prostate Imaging Reporting and Data System; PSAD: prostate-specific antigen density; CSPCa: clinically significant prostate cancer.
Sensitivity	88.64 (75.44 - 96.21)	85.19 (72.88 - 93.38)	82.81 (71.32 - 91.10)	75.00 (59.66 - 86.81)
Specificity	46.67 (33.67 - 60.00)	86.00 (73.26 - 94.18)	77.50 (61.55 - 89.16)	83.33 (71.48 - 91.71)
Positive likelihood ratio	1.66 (1.28 - 2.15)	6.08 (3.03 - 12.20)	3.68 (2.05 - 6.61)	4.50 (2.49 - 8.13)
Negative likelihood ratio	0.24 (0.10 - 0.58)	0.17 (0.09 - 0.33)	0.22 (0.13 - 0.39)	0.30 (0.18 - 0.51)
Disease prevalence	42.31 (32.68 - 52.39)	42.31 (32.68 - 52.39)	42.31 (32.68 - 52.39)	42.31 (32.68 - 52.39)
Positive predictive value	54.93 (48.46 - 61.23)	86.79 (76.62 - 92.95)	85.48 (76.62 - 91.36)	76.74 (64.63 - 85.63)
Negative predictive value	84.85 (70.15 - 93.03)	84.31 (73.74 - 91.14)	73.81 (61.61 - 83.19)	81.97 (72.91 - 88.48)
Accuracy	64.42 (54.43 - 73.57)	85.58 (77.33 - 91.70)	80.77 (71.87 - 87.84)	79.81 (70.81 - 87.04)

Table 7. Diagnostic Evaluation of PIRADS Score in Predicting CSPCa in Patients With Suspected PCa Using Criterion 1, Criterion 2 and Criterion 3

Clinical group

Clinically significant PCa with PIRADS scoring

Criteria 1

Criteria 2

Criteria 3

Criteria 4

Data shown as percentage (95% CI). CI: confidence interval; fPSA: free/total prostate specific antigen ratio; PCa: prostate cancer; PIRADS: Prostate Imaging Reporting and Data System; PSAD: prostate-specific antigen density; CSPCa: clinically significant prostate cancer.

Sensitivity

88.64 (75.44 - 96.21)

85.19 (72.88 - 93.38)

82.81 (71.32 - 91.10)

75.00 (59.66 - 86.81)

Specificity

46.67 (33.67 - 60.00)

86.00 (73.26 - 94.18)

77.50 (61.55 - 89.16)

83.33 (71.48 - 91.71)

Positive likelihood ratio

1.66 (1.28 - 2.15)

6.08 (3.03 - 12.20)

3.68 (2.05 - 6.61)

4.50 (2.49 - 8.13)

Negative likelihood ratio

0.24 (0.10 - 0.58)

0.17 (0.09 - 0.33)

0.22 (0.13 - 0.39)

0.30 (0.18 - 0.51)

Disease prevalence

42.31 (32.68 - 52.39)

Positive predictive value

54.93 (48.46 - 61.23)

86.79 (76.62 - 92.95)

85.48 (76.62 - 91.36)

76.74 (64.63 - 85.63)

Negative predictive value

84.85 (70.15 - 93.03)

84.31 (73.74 - 91.14)

73.81 (61.61 - 83.19)

81.97 (72.91 - 88.48)

Accuracy

64.42 (54.43 - 73.57)

85.58 (77.33 - 91.70)

80.77 (71.87 - 87.84)

79.81 (70.81 - 87.04)

**Table 8.** Summary of ROC Curve Analysis
PIRADS score criteria	AUC of ROC curve	P value	95% confidence interval
AUC: area under the ROC curve; PIRADS: Prostate Imaging Reporting and Data System; ROC: receiver operating characteristic.
Criteria 1	0.665	0.004	0.561	0.769
Criteria 2	0.827	< 0.001	0.743	0.910
Criteria 3	0.732	< 0.001	0.634	0.829
Criteria 4	0.792	< 0.001	0.699	0.884

Table 8. Summary of ROC Curve Analysis

PIRADS score criteria

AUC of ROC curve

P value

95% confidence interval

Lower bound

Upper bound

AUC: area under the ROC curve; PIRADS: Prostate Imaging Reporting and Data System; ROC: receiver operating characteristic.

Criteria 1

0.665

0.004

0.561

0.769

Criteria 2

0.827

< 0.001

0.743

0.910

Criteria 3

0.732

< 0.001

0.634

0.829

Criteria 4

0.792

< 0.001

0.699

0.884