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R
osa
MI
et
al
.
656
R
ev
A
ssoc
M
ed
B
ras
2017; 63(7):656-661
REVIEW ARTICLE
Urinary EN-2 to predict prostate cancer: Systematic review
and meta-analysis
M
aria
I
nês
da
R
osa
1,2,3
*, E
duardo
R
onconi
D
ondossola
1
, M
aria
C
ecilia
M
anenti
A
lexandre
1
, K
ristian
M
adeira
1
,
F
lorentino
de
A
raújo
C
ardoso
4
, A
ntonio
J
osé
G
rande
1,2
1
Epidemiology Laboratory, Universidade do Extremo Sul Catarinense (Unesc), Criciúma, SC, Brazil
2
Graduate Studies Program in Collective Health, Unesc, Criciúma, SC, Brazil
3
Graduate Studies Program in Health Sciences, Unesc, Criciúma, SC, Brazil
4
President of the Brazilian Medical Association
S
ummary
Study conducted at Laboratory
of Epidemiology, Universidade do
Extremo Sul Catarinense (Unesc),
Criciúma, SC, Brazil
Article received:
12/9/2016
Accepted for publication:
12/19/2016
*Correspondence:
Address: Rua Cruz e Souza, 510
Criciúma, SC – Brazil
Postal code: 88811-550
mir@unesc.net http://dx.doi.org/10.1590/1806-9282.63.07.656Introduction:
Prostate cancer is the second type of cancer diagnosed and the
fifth cause of death in men worldwide. Early diagnosis helps to control disease
progression. Currently, prostate specific antigen is the standard biomarker, as
it has a broad scope of identification and, thus, new and more specific biomarkers
must be studied.
Objective:
To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a
prostate cancer biomarker.
Method:
A comprehensive search was conducted in the period from January
2005 to July 2016 using the following electronic databases: Medline (PubMed),
Embase, Cochrane Library and Lilacs. The keywords used in the databases were:
“engrailed-2,” “EN2,” “prostatic neoplasms.” The search was limited to humans
and there was no language restriction. Critical appraisal of the included studies
was performed according to Quadas-2. Statistical analysis was performed using
Meta-DiSc® and RevMan 5.3 softwares.
Results:
A total of 248 studies were identified. After title and abstract screening,
231 studies were removed. A total of 17 studies were read in full and two studies
were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75)
and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97).
Conclusion:
The EN2 test showed high specificity (89%) and low sensitivity (66%).
Keywords:
prostatic neoplasms, biomarker, EN2, systematic review, meta-analysis.
I
ntroduction
Prostate cancer (PCa) is the fifth most frequent type of
cancer in the world and the second most diagnosed non-
cutaneous cancer in men in the United States according
to the International Agency for Cancer Research.
1
The disease has good prognosis when diagnosed at
an early stage, since it is responsive to various treatments.
Patients diagnosed with PCa at stage I, II, or III have a
high 5-year survival rate; however, patients with stage IV
cancer have a low 5-year survival rate of < 27%, highlight-
ing the importance of early detection.
2
Early stage PCa is often asymptomatic and the gold
standard test is prostate biopsy, which is usually indi-
cated in case of one or more of the following factors: fam-
ily history, abnormal lumps within the prostate by phys-
ical digital rectal examination, or an elevated serum
prostate-specific antigen (PSA).
3
PSA started to be used 30 years ago, and it is the most
common biomarker to diagnose and manage PCa. Despite
being used globally, it is important to mention that the
blood levels of PSA are often high in men with prostatic
benign conditions as well.
4
A recent systematic review of randomized controlled
trials of PSA screening for PCa concluded that screening
did not significantly decrease PCa-specific or overall mor-
tality, and showed that PSA can result in a high number
of false-positives, leading to overdiagnosis and overtreat-
ment.
5
Low specificity of PSA and unnecessary biopsies
are the most common problems of balancing benefits
and risks in tests.
6