Associations Between Serum Vitamin D and Adverse Pathology in Men Undergoing Radical Prostatectomy

Abstract

Purpose:
Lower serum vitamin D levels have been associated with an increased risk of aggressive prostate cancer. Among men with localized prostate cancer, especially with low- or intermediate-risk disease, vitamin D may serve as an important biomarker of disease aggression. The aim of this study was to assess the relationship between adverse pathology at the time of radical prostatectomy and serum 25-hydroxyvitamin D (25-OH D) levels.

Methods:
This cross-sectional study was carried out from 2009 to 2014, nested within a large epidemiologic study of 1,760 healthy controls and men undergoing prostate cancer screening. In total, 190 men underwent radical prostatectomy in the cohort. Adverse pathology was defined as the presence of primary Gleason 4 or any Gleason 5 disease, or extraprostatic extension. Descriptive and multivariate analyses were performed to assess the relationship between 25-OH D and adverse pathology at the time of prostatectomy.

Results:
Eighty-seven men (45.8%) in this cohort demonstrated adverse pathology at radical prostatectomy. The median age in the cohort was 64.0 years (interquartile range, 59.0 to 67.0). On univariate analysis, men with adverse pathology at radical prostatectomy demonstrated lower median serum 25-OH D (22.7 v 27.0 ng/mL, P = .007) compared with their counterparts. On multivariate analysis, controlling for age, serum prostate specific antigen, and abnormal digital rectal examination, serum 25-OH D less than 30 ng/mL was associated with increased odds of adverse pathology (odds ratio, 2.64; 95% CI, 1.25 to 5.59; P = .01).

Conclusion:
Insufficiency/deficiency of serum 25-OH D is associated with increased odds of adverse pathology in men with localized disease undergoing radical prostatectomy. Serum 25-OH D may serve as a useful biomarker in prostate cancer aggressiveness, which deserves continued study.

Full text

JOURNAL OF CLINICAL ONCOLOGY
ORIGINAL REPORT
Yaw A. Nyame, Cleveland Clinic,
Cleveland, Ohio; Adam B. Murphy, Diana
K. Bowen, Gregory Jordan, Michael
Dixon, Stephanie Kielb, Joshua J. Meeks,
and William J. Catalona, Northwestern
University, Chicago; Courtney M.P.
Hollowell, Cook County Health and
Hospitals System; Peter H. Gann, Virgilia
Macias, and Andre Kajdacsy-Balla,
University of Illinois at Chicago, Chicago,
IL; and Ken Batai and Rick Kittles,
University of Arizona, Tucson, AZ.
Published online ahead of print at
www.jco.org on February 22, 2016.
Supported by a grant from the US
Department of Defense W81XWH-10-1-
0532 pd22E (A.B.M.), and the following
National Institutes of Health grants:
1R01MD007105-01 (R.K.); IK2CX000926-01
(A.B.M.), and P50 CA 090386 -10S1 ( W.J.C.).
Y.A.N., A.B.M., and D.K.B. contributed
equally to the drafting of this manuscript.
Authors’ disclosures of potential conflicts
of interest are found in the article online at
www.jco.org. Author contributions are
found at the end of this article.
Corresponding author: Adam B. Murphy,
MD, Northwestern University, Tarry
Building Room 16–703, 300 E Superior,
Chicago, IL 60611; e-mail: a-murphy2@
northwestern.edu.
© 2016 by American Society of Clinical
Oncology
0732-183X/16/3412w-1345w/$20.00
DOI: 10.1200/JCO.2015.65.1463
Associations Between Serum Vitamin D and Adverse
Pathology in Men Undergoing Radical Prostatectomy
Yaw A. Nyame, Adam B. Murphy, Diana K. Bowen, Gregory Jordan, Ken Batai, Michael Dixon,
Courtney M.P. Hollowell, Stephanie Kielb, Joshua J. Meeks, Peter H. Gann, Virgilia Macias, Andre Kajdacsy-Balla,
William J. Catalona, and Rick Kittles
ABSTRACT
Purpose
Lower serum vitamin D levels have been associated with an increased risk of aggressive prostate
cancer. Among men with localized prostate cancer, especially with low- or intermediate-risk disease,
vitamin D may serve as an important biomarker of disease aggression. The aim of this study was to
assess the relationship between adverse pathology at the time of radical prostatectomy and serum
25-hydroxyvitamin D (25-OH D) levels.
Methods
This cross-sectional study was carried out from 2009 to 2014, nested within a large epidemiologic
study of 1,760 healthy controls and men undergoing prostate cancer screening. In total, 190 men
underwent radical prostatectomy in the cohort. Adverse pathology was defined as the presence of
primary Gleason 4 or any Gleason 5 disease, or extraprostatic extension. Descriptive and multi-
variate analyses were performed to assess the relationship between 25-OH D and adverse
pathology at the time of prostatectomy.
Results
Eighty-seven men (45.8%) in this cohort demonstrated adverse pathology at radical prostatectomy.
The median age in the cohort was 64.0 years (interquartile range, 59.0 to 67.0). On univariate analysis, men
with adve rse pathology at radical prostate ctomy demonstrated lower median serum 25-OH D (22.7 v
27.0 ng/mL, P = .007) compared with their counterparts. On multivariate analysis, controlling for age, serum
prostate specific antigen, and abnormal digital rectal examination, serum 25-OH D less than 30 ng/mL was
associated with increased odds of adverse pathology (odds ratio, 2.64; 95% CI, 1.25 to 5.59; P = .01).
Conclusion
Insufficiency/deficiency of serum 25-OH D is associated with increased odds of adverse pathology
in men with localized disease undergoing radical prostatectomy. Serum 25-OH D may serve as a
useful biomarker in prostate cancer aggressiveness, which deserves continued study.
J Clin Oncol 34:1345-1349. © 2016 by Ameri can Society of Clinical Oncology
INTRODUCTION
Recent population-based studies suggest that
there is a relationship between vitamin D defi-
ciency and increased prostate cancer (PCa) risk.
1
In addition, there is literature that demon-
strates that vitamin D deficiency is also associated
with aggressive PCa.
2,3
Interestingly, the preva-
lence o f vitamin D deficiency in a cohort of
meninChicago,Illinois—alowUVexposure
location—was 41. 2%, and the prevalence of
deficiency was significantly higher among
black men.
4
The relationship between v itamin
D and PCa may explain some disparities seen in
PCa, especially among black men.
The majority of men diagnosed with PCa in
the United States present with PCa localized to the
prostate gland. The current treatment paradigm is
shifting to managing these men w ith a surveil-
lance protocol. Active surveillance as a manage-
ment strategy of low-risk PCa—defined by the
criteria of Epstein et al
5
and D’Amico et al
6
—is an
evolving strategy that relies on risk stratification
and diagnostic testing. It is unclear whether there
are high-risk populations, such as black men, who
would benefit from additional screening tests
before management with a surveillance protocol.
However, useful clinical risk factors have been
extrapolated from pathologic findings from radical
prostatectomy specimens.
7,8
For example, a review
© 2016 by American Society of Clinical Oncology 1345
VOLUME 34
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APRIL 20, 2016
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Copyright © 2016 American Society of Clinical Oncology. All rights reserved.

of the radical prostatecto my database at Johns Hopkins Hospital
demonstrated that black men with very low-risk PCa were more likely
to have adverse pathology at prostatectomy compared with men of
Eur opean descent.
9
There is limited literature on the relationship between vitamin D
and pathologic findings at the time of radical pr ostatectomy.
10
The
aim of this study was to determine whether serum 25-hy dro xyvitamin
D (25-OH D) correlates with adverse pathology at radical prosta-
tectomy among a diverse population of men from a large, urban
population.
METHODS
This cross-sectional, observational study evaluating the associations of serum
25-OH D status with adverse pathology in men undergoing radical prosta-
tectomy was carried out from 2009 to 2014. It was nested within a large
epidemiologic study of 1,760 healthy controls and men undergoing PCa
screening that evaluated environmental and biologic mediators of vitamin D
and PCa risk. A total of 812 men between the ages of 40 and 79 years
underwent prostate core biopsy for increasing prostate specificantigen(PSA)
levels and/or an abnormal finding on digital rectal examination. All partic-
ipants wer e prospectively enr olled through outpatient urology clinics from
three academic (North western University, University of Chicago, Univ ersity of
Illinois at Chicago) and two public (Jesse Brown VA Medical Center and Cook
County Hospital) institutions in Chicago, Illinois.
One hundred ninety men were included in our study after under-
going radical prostatectomy for diagnosis of clinically localized PCa
within 1 year of their positive prostate biopsy. Genitourinary pathologists
reviewed all patholog ic specimens. Men with a diagnosis of PCa were
excluded from analysis if they received adjuvant therapy prior to radical
prostatectomy or if they underwent treatment at a nonstudy institution. All
study participants provided written consent, and the institutional review
board at each participating institution approved the protocol.
Clinical and Environmental Data
Trained research coordinators collected all patient data via patient
questionnaires and independent chart review. 25-OH D was collected by
a peripheral serum sample at the time of enrollment by a trained research
coor dinato r or clinic phlebotomis ts. Serum 25-OH D levels were measured
using the DiaSorin Liaison 25-OH Vitamin D TOTAL Assay platform
(DiaSorin, Stillwater, MN) by a direct, competitive chemiluminescent
immunoas say. Relev ant clin ical co va riates inclu ded age, first-degree family
history of PCa, and tobacc o use. Indicators of so cioeconomic sta tus were
collected through a combination of a questionnair e and medical record review .
Informatio n on ethnicity and race was collected by self-identification and was
characterizedasblack,white,orother.Inaddition,bodymassindex(BMI)was
calculated from the measurement of standing height (in meters) and weight (in
kilograms) of all participants at enrollment.
Cancer-specific clinical data, including biopsy result (ie, Gleason
score, number of positive cores, and percentage of core involvement),
clinical stage (tumor, node, metastasis classification), and PSA were
recorded, and men in the cohort were classified according to the National
Comprehensive Cancer Network (NCCN) risk classification groups.
11
Patients were then evaluated on the basis of the presence or absence of
adverse pathologic features at the time of radical prostatectomy. Adverse
pathology was defined by the presence of dominant Gleason pattern 4, the
presence of any pattern 5, and pathologic stage $ pT3aN0M0.
12
All
analyses were stratified by ethnicity/race and NCCN risk classification.
Statistical Analysis
Descriptive statistics were used to characterize important covariates,
including age, serum 25-OH D level, serum PSA level, race, BMI, tobacco
use, income, first-degree PCa family history, marital status, education, and
5 alpha-reductase inhibitor (5-ARI) use among men with and without
adverse pathology at radical prostatectomy. 5-ARI–adjusted PSA values
were calculated by doubling the prebiopsy PSA value.
13
A sample size of
190 patients—assuming a 1:1 case-control ratio—in a population with a
prevalence of adverse pathology of 35% had a power of 87.7% to detect an
OR of 2.5 or greater.
Continuous covariates were compared using a Wilcoxon rank sum
test, and categorical variables were compared using a x
2
test. Multivariate
analysis was conducted using binary logistic regression to further evaluate
the association of 25-OH D with adverse pathology. All multivariate
analyses were adjusted for season of blood draw (ie, high v low ultraviolet
exposure), race, and NCCN risk category. Covariates were added to the
model in an additive fashion, and covariates were kept in the model if P ,
.10. All statistical tests were two-sided, with significance defined at .05.
Additional regressions were conducted, stratified by NCCN category to
assess trends within risk groups. Statistical analyses were conducted with
Stata 12.1 (StataCorp, College Station, TX)
RESULTS
Overall, 45.8% (87) of the men in this cohort demonstrated
adverse p athology at radical prostatectomy. The median a ge of
men with adverse patholog y was 65.0 years (interquartile range
[IQR], 60.0 to 69.0 years), and the med ian age was 62.0 ye ars
(IQR, 60.0 to 69.0 years) for the men w ithout adverse patholog y
(P = .005). S imilarly, men w ith adverse pathology demonstrated
a statistically s ignificant higher median BMI (28.9 kg/m
2
v
27.7 kg/m
2
; P =.04)andserumPSA(6.8ng/mLv 4.4 ng/mL;
P , .001). In addition, men with adverse pathology at radical pros-
tatectomy demonstrated lower median serum 25-OH D (22.7 ng/mL;
IQR, 15.9 to 29.0) compared with their counterparts (27.0 ng/mL;
IQR, 20.0 to 34.0; P = .007). Men with adverse pathology were also
more likely to have a serum 25-OH D level less than 30 ng/ mL
(80.5% v. 57.3%; P = .001) and were more likely to self-identify as
black (P = .03). All other covariates did not demonstrate any
significant differences on analysis (Table 1).
Pretreatment patient characteristics are listed in Table 2.
Overall, 34.7% (66) of the men in this cohort met NCCN very low-
or low-risk criteria; 68.4% (130) of the men presented with cT1c
disease, 41.1% (78) had a Gleason score of 3 + 3 PCa, and 83.2%
(158) had a PSA level of less than 10 ng/mL. At the time of
prostatectomy, 31.6% of the men demonstrated extraprostatic
disease (pT3), with 10.0% having seminal vesicle invasion on final
pathology (Table 3).
On multiple logistic regression, a serum 25-OH D level of less than
30 ng/mL (odds ratio [OR], 2.51; 95% CI, 1.18 to 5.33; P =.02)was
associated with adverse pathology in a model controlling for age, serum
PSA, and abnormal findings on digital rectal examination (Table 4 ).
25-OH D as a continuous variable did not have a significant association
with adverse pathology for all men in the model. On stratified analysis,
serum 25-OH D level (OR, 0.92; 95% CI, 0.86-0.98; P = .01) and serum
25-OH D less than 30 ng/mL (OR, 3.62; 95% CI, 1.15 to 11.46; P = .03)
were significantly associated with adverse pa thology in men with
NCCN intermediate PCa at diagnosis. There were no significant
contributions to the models with race or season of blood draw
added. Additionally, no significant associations were observed on
multivariate analyses stratified by race/ethnicity with vitamin D.
1346 © 2016 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY
Nyame et al
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Copyright © 2016 American Society of Clinical Oncology. All rights reserved.

DISCUSSION
Serum 25-OH D was consistently associated with adverse patho-
logy on univariate and multivariate analysis in our cohort. Men
with adverse pathology had a 15.9% lower serum 25-OH D level
than did their counterparts. A 25-OH D level less than 30 ng/mL
was associated with increased odds of adverse pathology, even after
controlling for well-known preoperative risk factors of adverse
pathology, such as PSA level and disease palpable on digital rectal
examination.
6
This relationship seemed to be most pronounced
among men with intermediate risk disease on stratified analysis;
however, there was a nonsignificant association observed in men
with low and low NCCN risk disease preoperatively.
There is sparse literature on the association of circulating
serum 25-OH D and adverse pathology at the time of radical
prostatectomy. To our knowledge, there is only one other study
evaluating this relationship. Berg et al
10
reviewed 100 consecutive
men undergoing radical prostatectomy and did not find any
correlation between Gleason score, pathologic staging, or positive
margin status and vitamin D on multiple logistic regressions. The
study, however, is limited by a small sample size. Given our sample
size, we had 87% power to detect an OR greater than 2.5 for 25-OH D
levels less than 30 ng/mL and the presence of adverse pathology at
radical prostatectomy , assuming a 35% rate of adverse pathology .
12
The Berg et al
10
study would have been underpowered to assess for
this association, especially in adjusted analyses.
The correlation between vitamin D and PCa is being evaluated
among men in a variety of basic science and translation research
endeavors. Studies have demonstrated that PCa cells express the
vitamin D receptor, which acts as a substrate in the activation and
deactivation of many important cellular pathways.
14-16
Specifically,
vitamin D has been found to have an inhibitory effect on cellular
proliferation,
17,18
differentiation,
17-20
and apoptosis.
21-23
We have previously demonstrated an association of an increased
overall risk of PCa in blacks and aggressive/high-risk disease both
whites and blacks at the time of prostate biopsy among men with
low vitamin D levels.
3
Kristal et al
1
demonstrated a U-shaped
Table 1. Demogr aphic and Clinical Characteristics of Patients After Radical Prostatectomy
Characteristic Adverse Pathology (n = 87) Nonadverse Pathology (n = 103) P
Continuous, median (IQR)
Age, years 65.0 (60.0-69.0) 62.0 (58.0-66.0) .005*
Body mass index, kg/m
2
† 28.9 (26.2-32.0) 27.7 (25.0-29.8) .04*
Serum PSA 6.8 (5.0-11.8) 4.5 (3.8-6.0) , .001*
25-OH D serum level, ng/mL 22.7 (15.9-29.0) 27.0 (20.0-34.0) .007*
Categorical, %
First-degree family history of PCa (n = 184) 24.1 14.9 .57
Abnormal findings on DRE (n = 189) 44.2 18.5 , .001*
Race/ethnicity
Black (n = 45) 32.2 16.5
White (n = 128) 56.3 76.7
Other (n = 17) 11.5 6.7 .03*
High school diploma or equivalent 96.6 99.0 .24
25-OH D level, ng/mL
, 30 80.5 57.3 .001*
, 20 33.3 23.3 .12
, 12 16.1 7.8 .07
Vitamin D supplement use 16.1 22.3 .28
Married 75.9 76.7 .89
Obesity (n = 188)‡ 36.8 24.8 .07
Tobacco use, current 35.6 43.7 .26
5-ARI use (n = 187) 2.4 3.9 .54
NOTE. P values for continuous variables were derived from Wilcoxon rank-sum testing. P values for categorical variables were derived from x
2
analysis.
Abbreviations: 5-ARI, 5 alpha reductase inhibitor; 25-OH D, serum 25 hydroxyvitamin D; DRE, digital rectal examination; PCa, prostate cancer; PSA, prostate specific
antigen.
*Denotes statistic significance.
†BMI information was missing for one patient in this cohort.
‡Obesity was defined as a BMI $ 30 ng/mL.
Table 2. Pretreatment Characteristics of Patients in the Cohort (N = 190)
Characteristic No. (%)
Clinical TNM stage, N0/x, M0/x
cT1c 130 (68.4)
cT2a 32 (16.8)
cT2b 5 (2.6)
cT2c 23 (12.1)
Gleason score at initial biopsy
G3 + 3 78 (41.1)
G3 + 4 52 (27.3)
G4 + 3 28 (14.7)
$ G4 + 4 32 (16.8)
Serum PSA level (ng/mL)
# 10.0 158 (83.2)
10.1-20.0 24 (12.6)
. 20.0 8 (4.2)
NCCN risk criteria
Very low 21 (11.1)
Low 45 (23.7)
Intermediate 85 (44.7)
High 39 (20.5)
Abbreviations: NCCN, National Comprehensive Cancer Network; PSA, prostate
specific antigen; TNM, tumor, node, metastasis staging system.
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Vitamin D and Adverse Pathology at Radical Prostatectomy
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relationship between vitamin D and PCa risk on the basis of pro-
spective, multi-institutional data collected in the Selenium and
Vitamin E Cancer Prevention Trial. Similarly , Schenck et al
2
showed
an increased risk of aggressive PCa among men with low vitamin D.
Additionally, Steck et al
24
showed that low 25-OH D levels were
associated with aggressive PCa among black men in the North
Carolina-Louisiana Pr ostate Cancer Project, and this relationship was
modified negatively by low calcium intake. How ever, there are a
couple of methodological differences—such as timing of blood draw ,
which was several months after PCa diagnosis in their cohort, and
different risk strata definitions—that may explain disparities in some
of the results from our respective cohorts. Nonetheless, our findings
at the time of radical prostatectomy are consistent with the
observations from these studies because vitamin D deficiency was
associated with more aggressive disease findings at the time of
radical prostatectomy in men with localized PCa. Unfortunately,
Chicago, Illinois, is an ultraviolet-poor location, and elevated levels
of vitamin D did not occur in this cohort.
The initial assessment of our Chicago cohor t demonstrated
asignificant dispar ity regarding low vitamin D levels and black
race compared with white men in both univariate and multivariate
analyses. In fact, greater than 90% of black men in that study had
vitamin D levels less than 30 ng/mL.
4
Interestingly, black men show
a higher likelihood of progression and mor tality on active sur-
veillance for PCa.
25
Data from the Johns Hopkins Hospital group
suggest that failure on surveillance for black men may result from
adverse pathologic features, as demonstrated in low-risk black men
at the time of radical prostatectomy.
9
Unfortunately, we could not
verify any relationship between low serum vitamin D levels and
adverse pathology on race-stratified univariate or multivariate
analysis. Wes feel these analyses were significantly limited by a
lack of power due to t he relatively small size of each subgroup
analyzed.
In addition, studies show a decrease in PSA velocity in men
with advanced PCa receiving supplementation with calcitriol
and closely related v itamin D analogs.
27,28
The relationship
between serum 25-OH D and PSA l evels may be due to the effect
of vitamin D on PCa cell proliferation and differentiation. Our
findings showed that the largest association of low serum
vitamin D was a mong men with intermediate NCCN risk
disease at diag nosis. On the basis of the aforementioned data,
this g roup may benefit m ost from normalization of t heir
vitamin D levels w ith regard to their disease. Future studies
should evaluate the effect of vitamin D levels and supple-
mentation on PCa pathologic aggressiveness with regard to
NCCN r isk stratification, especially for men being considered
for active sur veillance, because vitamin D levels may be a useful
biomarker in this population.
In a clinical setting, men with insufficient or deficient levels of
25-OH D at the time of PCa diagnosis may benefit from sup-
plementation, with a goal of increasing serum 25-OH D levels to a
range of 30 to 55 ng/mL. This could be achieved by assessing the
serum vitamin D level at PCa diagnosis in all men with clinically
localized disease prior to supplementation. An open-label trial
of 4,000 IU of oral vitamin D3 in men undergoing active sur-
veillance for favorable risk PCa demonstrated a 55% decrease in the
number of positive biopsies or Gleason g rade at 1 year, w ith no
adverse events among men in the study.
26
However, we note that
our recommendation needs to be substantiated with a large,
randomized trial that would evaluate the impact of long-term
vitamin D supplementation in men diagnosed with localized PCa.
The limitations of this study include its cross-sectional study
design, which can lead to selection, observer, and analytical biases.
The authors recognized these limitations as part of nested, ret-
rospective analyses and adjusted for them by including all relevant
Table 4. Regressions for the Association of Adverse Pathology and Serum 25-OH D Less Than 30 ng/mL
Adverse Pathology: All
Men * (n = 189)
OR (95% CI)
Adverse Pathology:
NCCN Very Low/Low
Risk (n = 65) OR (95% CI)
Adverse Pathology:
NCCN Intermediate
Risk (n = 85) OR (95% CI)
Adverse Pathology:
NCCN High Risk (n = 39)
OR (95% CI)
Serum 25-OH D , 30 ng/mL 2.64 (1.25 to 5 .59)* 2.83 (0.54 to 14.89) 3.63 (1.15 to 11.46)* 5.73 (0.82 to 40.03)
Age 1.08 (1.02 to 1 .15)† 1.03 (0.92 to 1.15) 1.08 (0.99 to 1.20) 1.02 (0.81 to 1.29)
Serum PSA level 1.23 (1.11 to 1 .37)† 0.93 (0.67 to 1.30) 1.26 (1.08 to 1.46)† 1.16 (0.86 to 1.55)
Suspicious DRE 4.09 (1.91 to 8 .75)† 1.88 (0.28 to 12.51) 3.14 (1.06 to 9.26)§ —‡
Abbreviations: DRE, digital rectal examination; NCCN, National Comprehensive Cancer Network; 25-OH D, 25-hydroxyvitamin D; OR, odds ratio; PSA prostate specific antigen.
*One patient was removed from analysis for incomplete data for multivariate analysis.
†P , .01.
‡Abnormal DRE perfectly predicted adverse pathology in men with NCCN high-risk disease.
§P , .05.
Table 3. Surgical Pathologic Characteristics
Characteristic No. (%)
Pathologic TNM stage (N = 190)
pT2a 22 (11.6)
pT2b 4 (2.1)
pT2c 104 (54.7)
pT3a 41 (21.6)
pT3b 19 (10.0)
pNx 3 (1.6)
pN0 88 (46.6)
pN1 0 (0.0)
Pathologic Gleason score (N = 190)
G3 + 3 48 (25.4)
G3 + 4 75 (39.7)
G4 + 3 43 (22.8)
$ G4 + 4 41 (21.7)
Unknown 1 (0.01)
Adverse pathology by NCCN criteria (n = 87)
Very low/low risk 11 (12.7)
Intermediate risk 43 (49.4)
High risk 33 (37.9)
Abbreviations: NCCN, National Comprehensive Cancer Network; TNM, tumor,
node, metastasis staging system.
1348 © 2016 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY
Nyame et al
2016 from 165.124.224.157
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Copyright © 2016 American Society of Clinical Oncology. All rights reserved.

confounders. In addition, the sample size of the cohort diminished
the power of many of the stratified analyses. A one-time mea-
surement of serum 25-OH D has some limits as a proxy for overall
vitamin D status in patients. In addition, adjustment for season of
blood draw, which could confound associations with vitamin D
levels, did not change our results. Lastly, men treated with radical
prostatectomy at large, tertiary medical institutions may have
limited generalizability to men treated in other settings. None-
theless, our findings present new data that corroborate recent
associations between PCa aggressiveness and low vitamin D levels
demonstrated in a diverse population of men from a cohort in a
large urban city.
In conclusion, insufficiency/deficiency of 25-OH D is asso-
ciated with increased odds of adverse pathology in men with
localized disease undergoing radical prostatectomy. Men with
intermediate risk disease demonstrated the largest association
between serum vitamin D levels and adverse pathologic findings at
prostatectomy. Vitamin D could serve as an important biomarker
of adverse pathology in men with PCa, and the associations
between PCa aggressiveness and vitamin D deserve continued
exploration.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Disclosures provided by the authors are available with this article at
www.jco.org.
AUTHOR CONTRIBUTIONS
Conception and design: Yaw A. Nyame, Adam B. Murphy, Courtney M.P.
Hollowell, Stephanie Kielb, Joshua J. Meeks, Peter H. Gann, Andre
Kajdacsy-Balla, William J. Catalona, Rick Kittles
Provision of study materials or patients: Andre Kajdacsy-Balla, William
J. Catalona, Rick Kittles
Collection and assembly of data: Adam B. Murphy, Michael Dixon,
Virgilia Macias, Andre Kajdacsy-Balla, Rick Kittles
Financial support: Rick Kittles
Administrative support: Rick Kittles
Data analysis and interpretation: Yaw A. Nyame, Adam B. Murphy, Diana
K. Bowen, Gregory Jordan, Ken Batai, Virgilia Macias, Rick Kittles
Manuscript writing: All authors
Final approval of manuscript: All authors
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www.jco.org © 2016 by American Society of Clinical Oncology 1349
Vitamin D and Adverse Pathology at Radical Prostatectomy
2016 from 165.124.224.157
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Copyright © 2016 American Society of Clinical Oncology. All rights reserved.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Associations Between Serum Vitamin D and Adverse Pathology in Men Undergoing Radical Prostatectomy
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are
self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more
information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.
Yaw A. Nyame
No relationship to disclose
Adam B. Murphy
No relationship to disclose
Diana K. Bowen
No relationship to disclose
Gregory Jordan
No relationship to disclose
Ken Batai
No relationship to disclose
Michael Dixon
No relationship to disclose
Courtney M.P. Hollowell
No relationship to disclose
Stephanie Kielb
No relationship to disclose
Joshua J. Meeks
No relationship to disclose
Peter H. Gann
Research Funding: GlaxoSmithKline
Virgilia Macias
No relationship to disclose
Andre Kajdacsy-Balla
No relationship to disclose
William J. Catalona
Patents, Royalties, Other Intellectual Property: Co-inventor of urine
assay for prostate specific antigen enzymatic activity
Rick Kittles
No relationship to disclose
© 2016 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY
Nyame et al
2016 from 165.124.224.157
Information downloaded from jco.ascopubs.org and provided by at Northwestern Galter Health Sciences Library on May 12,
Copyright © 2016 American Society of Clinical Oncology. All rights reserved.