EURURO Vol. 72 No. 4

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considering bacteria, which may travel via the ascending
urethral route. However, it must be recognized that bacteria
may be able to localize in the most favorable ecological
niche of an organ also irrespectively of the entry route.
Having said that, in order to reduce potential biases
inherent to differences among prostate zones, we consid-
ered only specimens from the peripheral zone of the
prostate where the tumor preferentially occurs.
Our study is not devoid of limitations. First, it is not
possible to control for bacteria possibly introduced as part
of the transrectal biopsy procedure. Although remote, since
the composition of the colon microbiome is completely
different, this would remain a limit also in potential
prospective studies due to the difficulty to obtain consent
for extra biopsies to be devoted to research from diagnostic
sampling.
Within each tumor specimen, the area with the highest-
grade tumor has been sampled. In order to correctly
interpret the present findings, it must be recognized that
this choice does not allow to discern intra-specimen
differences in microbiome between high and low grade
diseases. As for the interspecimen differences, no correla-
tion with the grade, as well as the stage of the disease and
the findings reported were observed. This lack of correlation
may be also due to the limited number of cases; thereof, it
does not rule out the possibility that the tumor grade may
be associated to a different microbiome microenvironment.
As a consequence, studies on a wider number of cases,
stratified according to the stage and grade, will be necessary
to clarify this issue.
Being aware of the limit inherent in performing
statistical analysis only on 16 cases, we consider these
results of clinical relevance since they depict the microbial
microenvironment of the tumoral prostate gland, which is
per se an interesting and novel finding as it offers the
opportunity to consider the disease and its future manage-
ment from a different perspective.
Major strength of this analysis was the novel detailed
description of the microbiome environment specifically
associated to the tumor lesion and its surrounding areas,
thus highlighting the relevance the prostate prokaryotes
may have in the evolution of this disease. This keeps its
potential prospective importance despite having been
almost obliged to use only a relatively small amount of
samples, which could have possibly resulted in an
underestimation of our findings in terms of differences in
microbial diversity and accuracy in relative abundance.
Future studies are necessary to clarify the possible
pathogenic role of these specific bacteria and to assess their
potential to be exploited as new biomarkers.
5. Conclusions
This ultradeep pyrosequencing approach provided novel
findings of a large population of bacteria within the
prostate, never detected before using traditional standard
culture-based methods. Moreover, because of the ability to
analyze tissue environments with very low bacterial load,
we detected less abundant species below the previous
detectability; these observations pointed out subtle differ-
ences between a tumoral lesion and its surrounding tissues.
Overall, we consider these findings of crucial translational
relevance since they pave the way for future investigations
aimed to discover whether the specific prokaryotic inha-
bitants of the PCa microenvironment and/or their metab-
olites can be exploited as novel biomarkers and/or
therapeutic targets.
Author contributions: Filippo Canducci had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Canducci, Cavarretta, Salonia, Briganti.
Acquisition of data: Ferrarese, Saita, Lavorgna, Ceresola.
Analysis and interpretation of data: Cavarretta, Ferrarese, Cazzaniga,
Nebuloni.
Drafting of the manuscript: Cavarretta, Cazzaniga.
Critical revision of the manuscript for important intellectual content:
Salonia, Canducci, Cavarretta.
Statistical analysis: Ferrarese, Canducci.
Obtaining funding: None.
Administrative, technical, or material support: Locatelli, Doglioni, Visconti.
Supervision: Salonia, Montorsi, Clementi.
Other (sample collection and processing): Locatelli, Luciano` .
Financial disclosures: Filippo Canducci certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
Acknowledgments: The authors thank Olivia Morrow for reviewing
the language and Eugenio Ventimiglia for reviewing the statistical
analyses.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
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