EURURO Vol. 72 No. 4

493 656

In prostate cancer, intraductal carcinoma of the prostate
(IDC-P) is defined as growth of tumour cells within native
prostatic ducts and acini IDC-P is usually juxtaposed
with invasive adenocarcinoma, and a recent genomic study
showed that both histopathologies arise from a common
tumour clone . Tumours with IDC-P are also enriched for
copy number aberrations associated with poor prognosis
. This is consistent with the reporting of IDC-P in patients
with adverse pathological and clinical features . This
includes men with germline BRCA2 mutations, for which the
presence of IDC-P is associated with worse survival
outcomes . Despite this, reporting of IDC-P is not
widespread, and is predominantly confined to small patient
cohorts. Thus, IDC-P is often considered a rare feature of
prostate cancer and its potential therapeutic impacts have
not been fully elucidated. To define the overall prevalence of
IDC-P and its association with traditional features confer-
ring cancer risk, we performed a systematic review
investigating the prevalence of IDC-P across diverse
prostate cancer cohorts.
The systematic review was undertaken in accordance
with the Preferred Reporting Items for Systematic Review
and Meta-analysis (PRISMA) guidelines . The keywords
‘‘prostate cancer AND intraductal carcinoma’’ were used to
search the OVID Medline, PubMed and Scopus literature
databases in August 2016. This yielded 664 articles, which
were screened by study title and abstract, excluding articles
not in English, reviews, editorials, and letters. Two authors
independently reviewed the resulting 59 articles against
predetermined inclusion criteria. Studies were considered
eligible if they reported the prevalence of IDC-P within
patient cohort(s); and listed or cited histopathological
criteria used to identify IDC-P. On the basis of these criteria,
24 articles were included A). Eleven articles contained
more than one distinct patient cohort that were recorded
separately. Two patient cohorts were duplicated across
articles and were recorded only once in the systematic
review. Therefore, 38 data sets were included from the
24 articles ; Supplementary Table 1).
To compare the prevalence of IDC-P between different
patient populations, data sets were divided into four risk
categories on the basis of histopathological and clinical
features: low-risk, moderate-risk, high-risk, and metastatic
or recurrent disease (defined in . Thirty-four data
sets were assigned a category according to predicted risk
features. The remaining four data sets comprised patients
with known poor outcomes and were included in the
recurrent/metastatic category. Study details and patient
characteristics are listed in Supplementary Table 1.
In total, the 38 data sets involved 7279 patient speci-
mens, of which 1523 (20.9%) were positive for IDC-P
B). IDC-P was present in 13.7% of biopsies and 31.1% of
radical prostatectomies (Supplementary Fig. 1A,B). The
average prevalence of IDC-P was 2.1% in the low-risk
category, 23.1% in the moderate-risk category, 36.7% in the
high-risk category, and 56.0% in the recurrent/metastatic
disease risk category B). Compared to the low-risk
category, the prevalence of IDC-P was significantly greater
in both the high-risk (36.7 5.2%; p < 0.01) and the
recurrent/metastatic disease categories (56.0 9.9%;
p < 0.0001). Findings were consistent across prostate biopsies
and prostatectomy specimens ; Supplementary Fig.
1A,B). This demonstrates that IDC-P is highly prevalent in
patients at risk of poor outcomes, further supporting the
association between IDC-P and high-grade prostate cancer.
The appropriate clinical management of patients diag-
nosed with IDC-P has not been established. However, six
data sets evaluated the presence of IDC-P after patients
received androgen deprivation therapy and/or chemother-
apy (Supplementary Table 1). The average prevalence of
IDC-P in these cohorts was 59.7% (Supplementary Fig. 2).
The persistence of IDC-P following therapy has led to
speculation that it may be inherently resistant to treatment
; however, this requires further investigation.
This study demonstrates that IDC-P is variably present in
cohorts with diverse clinicopathological features. This may
have contributed to the commonly held misconception that
IDC-P is a rare pathology. Although it is true that IDC-P is
infrequent in low-risk cohorts, IDC-P is significantly more
frequent in patients with high-risk disease, rising to over
50% in patients who developed metastatic or recurrent
disease. Thus, IDC-P should not be disregarded.
Despite the prevalence of IDC-P in high-risk disease and
its association with poor clinical outcomes , it is currently
unknown whether IDC-P is simply a marker of aggres-
siveness or a mediator of disease progression. Recent
Table 1 – Data sets reporting the incidence of intraductal carcinoma of the prostate (IDC-P) according to risk category
Patient characteristics (one or more of the criteria listed)
Low risk Moderate risk High risk Metastatic or recurrent PC
No prior PC
diagnosis
GS 6
GS 7
Intermediate DARC
Cohort with varying GS
GS 8
High DARC
Germline BRCA2 mutation
or family history of cancer
Locally advanced disease (SVI, LNI)
Distant metastases at diagnosis
Biochemical recurrence
(median time to progression <4 yr)
Data sets (n) 5 14 12
Patients (n) 2255 3176 1214 634
Positive for IDC-P (%) 2.1 23.1 36.7 56.
DARC = D’Amico risk classification; GS = Gleason score; LNI = lymph node invasion; PC = prostate cancer; SVI = seminal vesicle invasion.
a For 4/7 data sets the outcome was known.
b The percentage of cases positive for IDC-P in the primary tumour.
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 9 2 – 4 9 5 493