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records of prescriptions; neither prescription compliance
nor over-the-counter aspirin were assessed.
A meta-analysis revealed that aspirin was associated
with lower overall PC incidence, with a stronger associa-
tion for advanced PCs (typically >T2, N1, or metastases)
. Hence, the effects of aspirin on locally advanced
pathogenesis versus metastases was not elucidated
The lower risk of lethal disease we found, but not
of overall, high-grade, or locally advanced PC, suggests
that previously observed protection against advanced
cancers might be limited to a reduction in metastatic
progression.
Mechanisms by which aspirin may protect against
lethality are largely unknown. Animal studies demonstrat-
ed that metastatic cancer cells need platelets to survive ,
and that platelet depletion can reduce metastases without
affecting primary tumor growth . While untested in
humans, this could account for weak associations between
aspirin and lethal PC in the lagged analyses and the lack
of duration-response associations.
Strengths of this study include repeated assessments and
long, nearly complete follow-up. The accuracy of reported
clinical information among physicians is probably high.
Limitations include the inability to explore dose-response
effects and inadequate statistical power in some secondary
analyses.
5. Conclusions
In this prospective study of 22 071 physicians, regular
prediagnostic aspirin use was associated with a lower risk of
lethal PC among all participants. Postdiagnostic use was
associated with improved survival after diagnosis. Aspirin
may inhibit PC progression, prolonging PC-specific and
overall survival. However, associations did not hold
throughout all sensitivity analyses; a randomized trial of
aspirin at PC diagnosis should be considered.
Author contributions: Mary K. Downer 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: Allard, Stampfer, Batista.
Acquisition of data: Allard, Downer, Stampfer, Batista.
Analysis and interpretation of data: Allard, Downer, Preston, Stampfer,
Mucci, Gaziano, Batista.
Drafting of the manuscript: Allard, Downer, Stampfer.
Critical revision of the manuscript for important intellectual content: Allard,
Downer, Preston, Stampfer, Mucci, Gaziano, Batista.
Statistical analysis: Allard, Downer.
Obtaining funding: Stampfer.
Administrative, technical, or material support: Stampfer.
Supervision: Stampfer, Batista.
Other: None.
Financial disclosures: Mary K. Downer 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,
consultancies, 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: This study received funding
from the Prostate Cancer Foundation and the National Cancer Institute
(CA34944, CA40360, CA141298, CA167552, HL26490, HL34595). The
sponsors played a role in the design and conduct of the study and in data
collection and management.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
.
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