

Platinum Priority – Editorial
Referring to the article published on pp. 942–949 of this issue
New Prostate Cancer Biomarkers: The Search Continues
Devin N. Patel, Stephen J. Freedland
*Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Although prostate-specific antigen (PSA) was originally
introduced as a tumor marker for detection of prostate
cancer recurrence or progression, its wider adoption in the
late 1980s and early 1990s changed prostate cancer
screening forever. PSA has been very useful for prostate
cancer screening; however, owing to limitations of poor
specificity and predictive values of total PSA assays, the
search for better biomarkers is an area of active research.
Towards this end, this issue of
European Urology
highlights
the work by Klein et al
[1]in developing the IsoPSA assay.
The authors, recognizing the benefits afforded by the
specificity of PSA to prostate tissue, explored the diagnostic
potential of its structural variants for detection of prostate
cancer.
PSA exists in the blood in multiple forms known as
isoforms. Some of these forms are more cancer-specific,
while others are less related to cancer. IsoPSA takes
advantage of these differences to detect isoform structures
that are more cancer-specific. While in concept this is similar
to free PSA and -2[Pro]PSA, the IsoPSA test analyzes all PSA
isoforms, both known and unknown, to categorize the
PSA isoform mixture into cancer and benign phenotypes.
Using this novel technology, Klein et al examined the
diagnostic accuracy of IsoPSA among 261men scheduled for
prostate biopsy in a multicenter setting. For detection of any
cancer on biopsy, the IsoPSA assay had significantly better
receiver operating characteristics (area under the curve
[AUC] 0.79) compared to total PSA (AUC 0.61;
p
<
0.001).
Similarly, for detecting high-grade prostate cancer (Gleason
7), the IsoPSA assay (AUC 0.81) outperformed total PSA
(AUC 0.69;
p
<
0.005). Moreover, relative to the Prostate
Cancer Prevention Trial Risk Calculator (PCPTRC) 2.0 risk
calculator, the IsoPSA assay had significant improvements
in decision curve analysis, showing that it offers net clinical
benefits relative to currently available calculators that use
only clinical features. Finally, use of an optimized cutoff
point for decision-making for biopsy would decrease
unnecessary biopsies by 45% while missing only 1.9% of
high-grade cancers.
While this study included men with prebiopsy PSA as
low as 2 ng/ml, the authors found less robust benefits of
IsoPSA in detecting high-risk cancer in these men with
lower risk. Specifically, unless the prebiopsy threshold
probability was
>
10% for high-grade disease, there was no
net benefit of using IsoPSA versus biopsying all men. In the
PCPT trial, the incidence of high-grade cancer among men
with PSA
<
4 ng/ml was approximately 6%, suggesting that
the IsoPSA assay may be most useful for patients with
higher PSA levels rather than those at the lower end of the
diagnostic ‘‘grey zone’’
[2] .Although the authors clearly showed that IsoPSA out-
performs currently used parameters, such as PSA, age, race,
and physical examination findings, their study also clearly
reveals the limitations of current risk calculators that rely
on these same clinical parameters. Indeed, in this study the
PCPTRC 2.0 calculator was worse than simply biopsying all
men. IsoPSA, along with other biomarkers, provides the
potential to improve these risk calculators in the future.
While IsoPSA provided important information, it should
be noted that there are numerous commercially available
biomarkers, all of which have been shown to offer improved
detection over PSA. These include PSA-based biomarkers
such as the Prostate Health Index (PHI) and the 4KScore
[3],
RNA-based biomarkers such as PCA3, SelectMDX and the
Mi-Prostate Score
[4–6], tissue-based biomarkers including
ConfirmMDx and the Prostate Core Mitomic test
[7,8], and
immune-based assays such as the APIFINY blood test
designed to detect prostate tumor–related autoantibodies
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 9 5 0 – 9 5 1available at
www.scienced irect.comjournal homepage:
www.europeanurology.comDOI of original article:
http://dx.doi.org/10.1016/j.eururo.2017.03.025.
* Corresponding author. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Los Angeles, CA 90048, USA.
Tel. +1 310 4234700; Fax: +1 310 4234711.
E-mail address:
stephen.freedland@cshs.org(S.J. Freedland).
http://dx.doi.org/10.1016/j.eururo.2017.04.0130302-2838/Published by Elsevier B.V. on behalf of European Association of Urology.