Table 1. Demographic and clinical characteristics of all study subjects who underwent the first prostate biopsy
|
Total
|
No cancer
|
Cancer
|
P value
|
|
N, 140
|
N, 77 (55%)
|
N, 63 (45%)
|
-
|
Median (interquartile range)
|
|
|
|
|
Age, yr
|
69.0 (10.0)
|
67.0 (9.0)
|
72.0 (10.0)
|
0.001
|
tPSA, ng/mL
|
6.93 (6.05)
|
6.45 (3.8)
|
8.18 (15.3)
|
0.010
|
fPSA
|
1.03 (0.92)
|
0.92 (0.8)
|
1.07 (1.4)
|
0.160
|
%fPSA
|
14.55 (9.29)
|
17.13 (8.0)
|
11.16 (9.0)
|
0.003
|
p2PSA, pg/mL
|
19.18 (30.97)
|
15.54 (16.7)
|
31.06 (58.6)
|
<0.001
|
%p2PSA
|
2.02 (2.21)
|
1.57 (1.5)
|
2.83 (2.6)
|
<0.001
|
PHI
|
45.90 (82.72)
|
39.54 (38.0)
|
91.18 (147.9)
|
<0.001
|
Positive core number
|
-
|
-
|
5.0 (7.0)
|
-
|
Number (percentage)
|
|
|
|
|
GS 6
|
-
|
-
|
15 (23.8%)
|
-
|
GS 7
|
|
|
18 (28.6%)
|
-
|
GS ≥8
|
|
|
30 (47.6%)
|
-
|
PSA = prostate-specific antigen, tPSA = total PSA, fPSA = free PSA, p2PSA = [2]proPSA, PHI = prostate health index, GS = Gleason score
Table 2. Descriptive characteristics of subjects with tPSA 4–10 ng/mL
|
Total
|
No cancer
|
Cancer
|
P value
|
|
N, 77
|
N, 48 (62.3%)
|
N, 29 (37.7%)
|
-
|
Median (interquartile range)
|
|
|
|
|
Age, yr
|
68.0 (12.0)
|
66.5 (11.0)
|
71.0 (12.0)
|
0.010
|
tPSA, ng/mL
|
6.41 (2.5)
|
6.42 (2.3)
|
6.13 (2.8)
|
0.877
|
fPSA
|
0.92 (0.5)
|
0.97 (0.6)
|
0.92 (2.4)
|
0.185
|
%fPSA
|
15.49 (8.6)
|
16.83 (7.5)
|
13.04 (7.1)
|
0.284
|
p2PSA, pg/mL
|
16.86 (17.5)
|
15.34 (16.1)
|
17.09 (23.7)
|
0.189
|
%p2PSA
|
1.61 ( 1.6)
|
1.50 (1.0)
|
2.35 (2.6)
|
0.015
|
PHI
|
41.35 (37.9)
|
39.65 (28.9)
|
53.72 (56.8)
|
0.018
|
Positive core number
|
-
|
-
|
4.0 (7.0)
|
-
|
Number (percentage)
|
|
|
|
|
GS 6
|
-
|
-
|
9 (31%)
|
-
|
GS 7
|
|
|
10 (34.5%)
|
-
|
GS ≥8
|
|
|
10 (34.5%)
|
-
|
PSA = prostate-specific antigen, tPSA = total PSA, fPSA = free PSA, p2PSA = [2]proPSA, PHI = prostate health index, GS = Gleason score
Table 3. Comparison between GS 6 disease and more aggressive disease in PCa patients
|
GS 6
|
GS ≥ 7
|
P value
|
|
N, 15 (23.8%)
|
N, 48 (76.2%)
|
-
|
Median (interquartile range)
|
|
|
|
Age, yr
|
73.0 (9.0)
|
72.0 (12.0)
|
0.520
|
tPSA, ng/mL
|
7.47 (4.6)
|
9.75 (23.6)
|
0.156
|
fPSA
|
0.97 (0.6)
|
1.13 (1.7)
|
0.358
|
%fPSA
|
13.08 (8.0)
|
10.98 (9.2)
|
0.302
|
p2PSA, pg/mL
|
13.9 (13.4)
|
45.3 (72.6)
|
0.001
|
%p2PSA
|
1.26 (1.0)
|
3.17 (2.2)
|
<0.001
|
PHI
|
35.4 (28.0)
|
120.8 (148.6)
|
<0.001
|
Positive core number
|
3.0 (4.0)
|
6.0 (6.0)
|
0.032
|
PSA = prostate-specific antigen, tPSA = total PSA, fPSA = free PSA, p2PSA = [2]proPSA, PHI = prostate health index, GS = Gleason score
Table 4. Logistic regression analyses predicting the probability of prostate cancer.
Predictors
|
AUC of individual predictor variable (95% CI);
P value*
|
Bivariate analysis
OR(95%CI);
P value
|
Multivariate analysis
|
Base model**
OR(95% CI); P value
|
Base model + %p2PSA
OR (95% CI); P value
|
Base model + PHI
OR(95%CI); P value
|
tPSA, ng/mL
|
0.63
(0.54 –0.71) -
|
1.100
(1.04–1.16); 0.001
|
1.084
(0.98–1.20); 0.137
|
1.067
(0.97 –1.18); 0.197
|
1.030
(0.94–1.13); 0.514
|
fPSA
|
0.57
(0.48 - 0.65) 0.117
|
1.543
(1.06–2.25); 0.024
|
1.017
(0.50–2.09); 0.962
|
1.015
(0.51–2.04); 0.966
|
0.898
(0.47–1.72); 0.745
|
%fPSA
|
0.69
(0.61 - 0.77) 0.203
|
0.927
(0.88–0.98); 0.004
|
0.961
(0.89–1.04); 0.330
|
0.965
(0.89–1.04); 0.357
|
0.975
(0.91–1.05); 0.507
|
p2PSA, pg/mL
|
0.69
(0.60 - 0.76) 0.157
|
1.021
(1.01–1.04);
0.001
|
-
|
-
|
-
|
%p2PSA
|
0.71
(0.63 - 0.78) 0.155
|
1.612
(1.26–2.07); < 0.001
|
-
|
1.432
(1.11–1.84); 0.005
|
-
|
PHI
|
0.75
(0.67 - 0.82) 0.005
|
1.015
(1.01–1.02); < 0.001
|
-
|
-
|
1.013
(1.00–1.02); 0.004
|
AUC of multivariate models (95% CI);
|
-
|
-
|
0.691
(0.60–0.78)
|
0.757
(0.68–0.84)
|
0.765
(0.69–0.84)
|
Gain in predictive accuracy (95% CI);
P value
|
-
|
-
|
-
|
0.066
(0.02–0.11);
<0.001
|
0.074
(0.02–0.12);
<0.001
|
*P value : Comparison of AUC using tPSA as standard
**Base model includes age, tPSA, and %fPSA.
AUC, area under the receiver operating characteristic curve; PSA, prostate-specific antigen; fPSA, free PSA; p2PSA, [-2]proPSA; PHI, prostate health index; tPSA, total PSA
OR = odds ratio, CI = confidence interval.
Table 5. Logistic regression analyses predicting the probability of prostate cancer in subjects with tPSA 4–10 ng/mL
Predictors
|
AUC of individual predictor variable (95% CI);
P value*
|
Bivariate analysis
OR(95%CI);
P value
|
Multivariate analysis
|
Base model
OR (95%CI); P value
|
Base model + %p2PSA
OR (95% CI); P value
|
Base model + PHI
OR(95%CI); P value
|
tPSA, ng/mL
|
0.50
(0.38 - 0.61) -
|
1.024
(0.76–1.38); 0.875
|
1.486
(0.67–3.30); 0.330
|
1.147
(0.48 –2.75); 0.758
|
1.065
(0.44–2.58); 0.888
|
fPSA
|
0.59
(0.47 -0.70) 0.418
|
0.529
(0.18–1.53); 0.240
|
0.057
(0.00–9.73); 0.275
|
0.200
(0.00–47.1); 0.564
|
0.216
(0.00–51.3); 0.583
|
%fPSA
|
0.63
(0.52 - 0.74) 0.090
|
0.961
(0.89–1.03); 0.284
|
1.161
(0.82–1.64); 0.394
|
1.076
(0.75–1.54); 0.689
|
1.071
(0.75–1.53); 0.706
|
p2PSA, pg/mL
|
0.59
(0.47 - 0.70) 0.286
|
1.023
(1.00–1.05); 0.089
|
-
|
-
|
-
|
%p2PSA
|
0.67
(0.55 - 0.77) 0.075
|
1.539
(1.09-2.16); 0.031
|
-
|
1.529
(1.08–2.17); 0.035
|
-
|
PHI
|
0.69
(0.55 - 0.78) 0.054
|
1.015
(1.00–1.03); 0.027
|
-
|
-
|
1.015
(1.00–1.03); 0.027
|
AUC of multivariate models (95% CI);
|
-
|
-
|
0.594
(0.47–0.72)
|
0.683
(0.56–0.80)
|
0.695
(0.55–0.80)
|
Gain in predictive accuracy (95% CI);
P value
|
-
|
-
|
-
|
0.089
(0.02–0.14);
0.015
|
0.101
(0.07–0.17);
0,010
|
*P value : Comparison of AUC using tPSA as standard
**Base model includes age, tPSA, and %fPSA.
AUC, area under the receiver operating characteristic curve; PSA, prostate-specific antigen; fPSA, free PSA; p2PSA, [-2]proPSA; PHI, prostate health index; tPSA, total PSA
OR = odds ratio, CI = confidence interval.
Table 6. Logistic regression analyses predicting the probability of Gleason score ≥ 7 disease
Predictors
|
AUC of individual predictor variable (95% CI);)
P value*
|
Bivariate analysis
OR(95%CI); P value
|
Multivariate analysis
|
Base model
OR(95% CI); P value
|
Base model + %p2PSA
OR (95% CI); P value
|
Base model + PHI
OR(95%CI); P value
|
tPSA, ng/mL
|
0.62
(0.48 - 0.77) 0.156
|
1.064
(0.99–1.14); 0.086
|
1.031
(0.92–1.16); 0.601
|
1.022
(0.95–1.11); 0.583
|
0.978
(0.91–1.06); 0.572
|
fPSA
|
0.58
(0.44 - 0.72) 0.358
|
1.818
(0.84–3.94); 0.129
|
1.413
(0.39–5.11); 0.598
|
0.962
(0.34–2.74); 0.942
|
0.745
(0.28–2.00); 0.559
|
%fPSA
|
0.41
(0.26 - 0.57) 0.302
|
0.973
(0.91–1.04); 0.440
|
0.977
(0.88–1.09); 0.678
|
0.989
(0.87–1.12); 0.861
|
1.014
(0.90–1.14); 0.814
|
p2PSA, pg/mL
|
0.79
(0.68 - 0.91) 0.001
|
1.047
(1.01–1.09); 0.017
|
-
|
-
|
-
|
%p2PSA
|
0.87
(0.75 - 0.99) <0.001
|
3.887
(1.73-8.74); 0.009
|
-
|
3.530
(1.50–8.34); 0.021
|
-
|
PHI
|
0.88
(0.76 - 0.99) <0.001
|
1.020
(1.01–1.04); 0.007
|
-
|
-
|
1.028
(1.01–1.05); 0.015
|
AUC of multivariate models (95% CI)
|
-
|
-
|
0.640
(0.49–0.79)
|
0.879
(0.76–1.00)
|
0.881
(0.73–0.99)
|
Gain in predictive accuracy (95% CI);
P value
|
-
|
-
|
-
|
0.239
(0.10–0.26);
<0.001
|
0.241
(0.10–0.27);
<0.001
|
*P value : Comparison of AUC using tPSA as standard
**Base model includes age, tPSA, and %fPSA.
AUC, area under the receiver operating characteristic curve; PSA, prostate-specific antigen; fPSA, free PSA; p2PSA, [-2]proPSA; PHI, prostate health index; tPSA, total PSA
OR = odds ratio, CI = confidence interval.
Table 7. The number of biopsies that could be avoided and characteristics of missed cancers at cut-off of 90% sensitivity of the markers in subjects with tPSA 4–10 ng/mL
Marker
|
Cut-off at 90%
sensitivity
|
% Specificity
|
Unnecessary
biopsy avoided
|
Missed cancer
|
Total
|
Missed GS 6
|
Missed GS 7
|
Missed GS ≥8
|
|
Total PSA 4–10 ng/mL
|
%fPSA
|
≤7.86
|
9%
|
4
(5.2%)
|
3 (10.3%)
|
0
(0%)
|
1 (3.5%)
|
2 (6.8%)
|
p2PSA
(pg/mL)
|
≥8.08
|
17%
|
7
(9.1%)
|
3 (10.3%)
|
2
(6.8%)
|
0
(0%)
|
1 (3.5%)
|
%
p2PSA
|
≥1.20
|
27%
|
12
(15.5%)
|
3 (10.3%)
|
3 (10.3%)
|
0
(0%)
|
0
(0%)
|
PHI
|
≥26.33
|
25%
|
9
(11.7%)
|
2
(6.8%)
|
2
(6.8%)
|
0
(0%)
|
0
(0%)
|
|
All study subjects
|
%fPSA
|
≤6.42
|
7%
|
6
(4.3%)
|
7 (11.1%)
|
0
(0%)
|
2 (3.2%)
|
5 (7.9%)
|
p2PSA
(pg/mL)
|
≥8.07
|
20%
|
16
(11.4%)
|
7 (11.1%)
|
4
(6.3%)
|
2 (3.2%)
|
1 (1.6%)
|
%
p2PSA
|
≥1.22
|
31%
|
24
(17.1%)
|
7 (11.1%)
|
7 (11.1%)
|
0
(0%)
|
0
(0%)
|
PHI
|
≥33.40
|
40%
|
32
(22.9%)
|
5
(7.9%)
|
5
(7.9%)
|
0
(0%)
|
0
(0%)
|
PSA, prostate-specific antigen; fPSA, free PSA; p2PSA, [-2]proPSA; PHI, prostate health index