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Prostate Cancer
Table 1: Correlation of Prostate Cancer Gene Score and
samples revealed a ROC–AUC of 0.66 for PCA3 score versus 0.57 for PSA.
Tumour Volume
13
The sensitivity of the PCA3 urine test was 65% and the specificity was
66%. In this group, the largest studied thus far using a PCA3 gene-based
Tumour Volume
test, it was demonstrated that if used as a reflex test a PCA3 score can
<0.5cc (A) >0.5 to <2cc (B)>2cc (C)
improve specificity and may prevent many unnecessary prostate biopsies.
Median 21.5 41.8 48.1
Mean 29.3 54.4 69.9
p value A versus B: 0.002 A versus C: 0.001
This may also be the case for repeat biopsies. In a recent study, the PCA3
scores were determined using a highly sensitive quantitative assay with
of 79%. This was superior to the serum PSA assay (cut-off level 2.5ng/ml), transcription-mediated amplification in 226 men who had informative
which had a sensitivity of 81% and a specificity of only 28%. urine specimens with serum PSA levels persistently >2.5ng/ml and at least
one previous negative biopsy.
17
A repeat biopsy revealed prostate cancer
These results were similar to the findings of a previous study. In a cohort in 27% of the subjects. ROC analysis yielded an AUC of 0.68 for the
of 108 pre-biopsy patients, the AUC–ROC of PCA3 ratio was 0.717, with PCA3 score and 0.52 for serum PSA. Using a PCA3 score cut-off of 35,
a sensitivity and specificity of 67 and 83%, respectively.
6
In a more recent the assay sensitivity was 58% with a specificity of 72%. Furthermore, at
update of their data, Hessels et al. reported the sensitivity and specificity PCA3 scores of less than five, only 12% of men had prostate cancer on
of the test as 50 and 77%, respectively, in a group of 299 patients who repeat biopsy; this is in contrast to scores greater than 100, where the
underwent prostate biopsy.
11
These investigators had also demonstrated risk of positive biopsy was 50%.
that the PCA3 test could be performed on both urine and prostatic fluid
with comparable diagnostic results.
12
Similarly, in a prospective multicentre European trial, men with one or
two prior negative biopsies were evaluated with PCA3 score before
repeat biopsy.
18
Preliminary data from 225 men revealed prostate cancer
in 29% of the cases on repeat biopsy. The specificity and negative
Fradet et al. reported a similar
predictive value of the PCA3 test in this population were 74 and 79%,
performance of the PCA3 test,
respectively, when the cut-off level was set at 35. The probability of
finding prostate cancer was doubled in patients with a score of >35
with a sensitivity and specificity
(41%) compared with those if the score was <35 (21%). The PCA3 score
of 66 and 89%, respectively.
was superior to serum PSA determination for predicting the outcome in
this repeat biopsy setting as well. Therefore, PCA3 testing may enhance
the ability of determining those patients with a higher probability of
prostate cancer on repeat biopsy.
Nakanishi et al.
13
assessed the expression of urinary PCA3 to PSA mRNA
ratio. The results of this study indicated a significantly higher median PCA3 Early Prostate Cancer Antigen
score in patients with prostate cancer (median PCA3 score of 31) Early prostate cancer antigen (EPCA) is a nuclear matrix protein
compared with cases with negative biopsies (median PCA3 score of 21.1; identified in prostate cancer. Detection of this protein by enzyme-
p=0.029). This also correlated significantly with total tumour volume in linked immunosorbent assay (ELISA) in men with prostate cancer was
prostatectomy specimens (p=0.008) (see Table 1) as well as Gleason score possible; however, EPCA was absent in age-matched sera from organ
(6 versus >7; p=0.005). A multivariate analysis of the data indicated PCA3 donors or men with other malignancies.
19
Further research identified
as the most significant predictor of low-volume disease (AUC–ROC 0.757). another unrelated antigen (EPCA-2) associated with the nuclear
structure of prostate cancer cells.
19–21
In a prospective study that enrolled 201 patients, urine samples were
collected after attentive digital rectal palpation prior to prostate
biopsy.
14
A single void specimen of 20–30ml used for extraction of
Further research identified another
DD3 (PCA3) RNA and PSA mRNA and amplification was performed
using isothermic-nucleic-acid-based amplification. The two targets
unrelated antigen (early prostate
were detected in realtime, using specific beacons as probes in a cancer antigen-2) associated with
thermostated spectrofluorimeter. Prostate cancer was found in 62
the nuclear structure of prostate
(39%) of the 158 evaluable patients. The sensitivity of the PCA3 score
by this method was found to be 82% at a cut-off value of 50x10
-3
, cancer cells.
with a specificity of 76%. The AUC was 0.87 (confidence interval (CI)
0.81–0.92). In comparison, these values were 98 and 5%, respectively,
for total PSA with a cut-off level of 2.5ng/ml. Thus, the PCA3 score Using an indirect ELISA assay, Paul et al. compared plasma samples from
showed excellent clinical performance and a specificity much better prostate cancer patients with samples from healthy donors, patients with
than PSA. Using a different assay in a group of 443 men, Fradet et al. other malignancies and those with benign urological conditions.
19
The
reported a similar performance of the PCA3 test, with a sensitivity and authors chose a pre-determined cut-off level of 1.7 absorbance based on
specificity of 66 and 89%, respectively.
15
the measurements of plasma EPCA in prostate cancer patients and a
healthy donor training set. An analysis of the data showed a highly
A prospective multicentre study investigated the validity of this test
16
in a significant difference in plasma EPCA levels in prostate cancer patients
larger patient population. Analysis of data from 534 men with informative compared with healthy donors (p<0.0001), bladder cancer patients
14 EUROPEAN GENITO-URINARY DISEASE 2007
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