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Clinical performance of serum isoform [-2]proPSA (p2PSA) and its derivatives,
namely %p2PSA and PHI (Prostate Health Index) in men younger than 60 years of
age. Results from a multicentric European study (PROMEtheuS project).
VILLA ROMANAZZI CARDUCCI
Via Capruzzi, 326 - 70124 Bari (IT)
MASSIMO LAZZERI - NICOLA FOSSATI - ALESSANDRO LARCHER - ALBERTO ABRATE GIOVANNI LUGHEZZANI - GIORGIO GUAZZONI
Dipartimento di Urologia, San Raffaele Turro, Università Vita-Salute San Raffaele, Milano
%p2PSA
Index tests
PHI
tPSA
Reference
standard tests
fPSA
f/tPSA
SCOPO DELLO STUDIO
Confrontare il [-2]proPSA (p2PSA) e i suoi derivati, %p2PSA e PHI (prostate health index)
con I test di riferimento (tPSA, fPSA e %fPSA) nel rilevare un Carcinoma Prostatico (Pca) in
pazienti giovani (<60 anni).
[-2]PROPSA AND DERIVATES
PHI
%p2PSA
p2PSA
free PSA
× √tPSA]
(p2PSA pg/ml)
(free PSA ng/ml × 1000)] × 100)
MATERIALI E METODI
STIUDY DESIGN: a nested case sontrol from the PRO-psa
Multicentric European Study (Prometetheus)
PRIMARY OUTCOMES: to test the sensibility, specificity and
accuracy of serum p2PSA, percentage of p2PSA to fPSA (%p2PSA)
and Beckman Coulter PHI (Prostate Health Index) in men younger
than 60 years of age who had undergone prostatic biopsy for
suspected Pca.
STATISTICAL ANALYSIS: multivariable logistic regression models
were complemented by predictive accuracy analysis and decision
curve analysis.
RISULTATI
Overall
Absence of PCa
Presence of PCa
238
171 (71.9%)
67 (28.1%)
PREDICTORS
!
AUC of
individual
predictor
variables
(95% CI)
Multivariate analysis
Bivariate analysis
Base model
Base model plus
p2PSA
Base model plus
%p2PSA
OR (95% CI);
p-value
OR (95% CI);
p-value
OR (95% CI);
p-value
OR (95% CI);
p-value
Base model plus
PHI
OR (95% CI);
p-value
1.054 (1.003-1.108);
p=0.042
0.981 (0.952-1.011);
p=0.146
1.067 (0.943-1.207);
p=0.221
0.971 (0.954-0.988);
p=0.009
1.047 (0.907-1.209);
p=0.425
0.970 (0.944-0.997);
p=0.039
1.052 (0.911-1.214);
p=0.386
0.981 (0.919-1.359);
p=0.012
1.039 (0.894-1.207);
p=0.521
0.979 (0.958-1.000);
p=0.051
-
-
-
-
1.152 (0.896-1.480);
p=0.193
0.745 (0.345-1.611);
p=0.349
1.000 (0.996-1.004);
p=0.973
1.125 (0.905-1.399);
p=0.207
0.303 (0.048-1.899);
p=0.145
0.999 (0.996-1.002);
p=0.406
1.090 (1.005-1.182);
p=0.042
1.117 (0.919-1.359);
p=0.190
1.019 (0.510-2.035);
p=0.945
0.999 (0.996-1.002);
p=0.339
1.007 (0.908-1.118);
p=0.853
0.945 (0.442-2.018);
p=0.846
1.001 (0.998-1.005);
p=0.357
-
-
Age
0.58 (0.50-0.66)
Prostate volume
0.66 (0.58-0.73)
Adenoma
volume1
0.66 (0.58-0.73)
0.954 (0.906-1.006);
p=0.068
tPSA
0.55 (0.48-0.61)
fPSA
0.51 (0.45-0.58)
%fPSA2
0.56 (0.49-0.62)
p2PSA
0.61 (0.54-0.67)
%p2PSA
0.70 (0.64-0.76)
PHI
0.70 (0.64-0.76)
1.062 (0.968-1.165);
p=0.147
1.248 (0.876-1.776);
p=0.157
0.997 (0.992-1.001);
p=0.117
1.042 (1.009-1.076);
p=0.024
2.267 (1.373-3.743);
p=0.011
1.035 (1.010-1.061);
p=0.018
-
-
2.254 (1.052-4.830);
p=0.042
-
-
-
-
1.041 (1.007-1.075);
p=0.028
AUC of multivariate models (95% CI)
0.690 (0.627-0.755)
0.755 (0.691-0.811)
0.757 (0.694-0.814)
0.770 (0.707-0.825)
Gain in predictive accuracy (95% CI)
-
0.061 (0.008-0.113)*
0.063 (0.007-0.120)*
0.076 (0.012-0.140)*
RISULTATI
Receiver operating characteristic curves depicting the accuracy of individual
predictors of prostate cancer at initial extended biopsies.
Cut - Off
Criterion
Sensitivity (%)
95%C.I.
Specificity (%)
95%C.I.
PPV
95%C.I.
NPV
95%C.I.
≥2.55
≥5.72
≥11.68
91.0
52.2
20.9
81.5-96.6
39.7-64.6
11.9-32.6
10.5
52.0
90.6
6.4-16.1
44.3-59.7
85.2-94.6
28.5 22.5
29.9 21.6
46.7 28.8
- 34.6
- 38.2
- 64.5
75.0
73.6
74.5
57.7 65.7 68.6 -
92.3
81.4
80.4
≤2.55
≤0.76
≤0.35
92.5
55.2
9.0
83.4-97.5
42.6-67.4
3.4-18.5
2.3
57.9
92.4
0.7-5.9
50.1-65.4
87.3-95.9
27.1 21.3
33.9 25.1
31.6 10.7
- 32.8
- 42.8
- 52.5
44.4
76.7
72.1
12.0 69.5 66.2 -
76.9
84.0
78.1
≤0.233
≤0.140
≤0.098
91.0
52.2
29.2
81.5-96.6
39.7-64.6
25.0-33.7
9.9
54.4
90.1
5.9-15.4
46.6-62.0
87.5-92.4
28.4 22.3
31.0 22.4
54.1 38.0
- 34.4
- 39.5
- 70.1
73.9
74.4
76.6
56.0 66.7 70.8 -
91.9
82.1
82.5
≥7.6
≥14.5
≥25.1
91.0
56.7
28.4
81.5-96.6
44.0-68.8
18.0-40.7
16.4
54.4
90.6
11.2-22.8
46.6-62.0
85.2-94.6
29.9 23.6
32.8 24.2
54.3 37.8
- 36.2
- 41.3
- 70.8
82.4
76.2
76.4
69.5 68.7 70.5 -
95.2
83.8
82.2
≥1.37
≥1.86
≥2.63
90.0
65.7
28.4
81.5-96.6
53.1-76.8
18.0-40.7
33.3
65.5
90.6
26.3-40.9
57.9-72.6
85.2-94.6
34.5 27.4
42.7 33.2
54.3 37.8
- 41.5
- 52.3
- 70.8
89.1
83.0
76.4
81.4 76.6 70.5 -
96.7
89.3
82.2
≥29.2
≥41.2
≥60.9
91.0
64.2
37.3
81.5-96.6
51.5-75.5
25.8-50.0
11.1
63.2
90.0
6.8-16.8
55.5-70.4
84.6-94.1
28.6 22.6
40.6 31.2
59.5 44.7
- 34.7
- 49.9
- 74.4
76.0
81.8
78.6
59.3 75.2 72.8 -
92.7
88.4
84.3
Total PSA (ng/mL)
Free PSA (ng/mL)
%fPSA
[-2]proPSA (pg/mL)
%[-2]proPSA
PHI
!
Avoided Biopsies
Models builded on subjects with prostate volume and age data (211, 155 Not Cancer, 56 Cancer)
Model 1
Cancer
probability
threshold (%)
10
20
30
40
50
Model 2
Model 3
Model 4
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
15
48
108
138
152
9.7
31.0
69.7
89.0
98.1
0
10
22
38
47
0.0
17.9
39.3
67.9
83.9
21
76
120
137
146
13.5
49.0
77.4
88.4
94.2
0
9
22
32
38
0.0
16.1
39.3
57.1
67.9
14
78
122
138
146
9.0
50.3
78.7
89.0
94.2
0
10
25
35
38
0.0
17.9
44.6
62.5
67.9
20
79
123
139
146
12.9
51.0
79.4
89.7
94.2
Missed
cancers
10
23
31
37
%
0.0
17.9
41.1
55.4
66.1
Estimate on overall subjects (238; 171 Not Cancer, 67 Cancer)
Model 1
Cancer
probability
threshold (%)
10
20
30
40
50
Model 2
Model 3
Model 4
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
Missed
cancers
%
Avoided
biopsies
%
Missed
cancers
%
17
53
119
152
168
9.9
31.0
69.6
88.9
98.2
0
12
26
45
56
0.0
17.9
38.8
67.2
83.6
23
84
132
151
161
13.5
49.1
77.2
88.3
94.2
0
11
26
38
45
0.0
16.4
38.8
56.7
67.2
15
86
135
152
161
8.8
50.3
78.9
88.9
94.2
0
12
30
42
45
0.0
17.9
44.8
62.7
67.2
22
87
136
153
161
12.9
50.9
79.5
89.5
94.2
0
12
28
37
44
0.0
17.9
41.8
55.2
65.7
Percentages are calculated on total not cancer subjects for avoided biopsies, and on total cancer subjects for missed cancer
!
CONCLUSIONI
Our findings showed that %p2PSA and PHI are
more accurate than the reference standard tests
(tPSA, fPSA and %fPSA) in predicting PCa in men
younger than 60 years of age and may also be
indicative of cancer aggressiveness.
These results should be taken into account when
considering PCa screening studies in young
patients.
Clinical performance of serum isoform [-2]proPSA (p2PSA) and its derivatives,
namely %p2PSA and PHI (Prostate Health Index) in men younger than 60 years of
age. Results from a multicentric European study (PROMEtheuS project).
MASSIMO LAZZERI (1) - NICOLA FOSSATI (1) - ALESSANDRO LARCHER (1) - ALBERTO
ABRATE (1) - GIOVANNI LUGHEZZANI (2) - GIORGIO GUAZZONI (1)
Dipartimento di Urologia, San Raffaele Turro, Università Vita-Salute San Raffaele, Milano