Prostate Cancer and Prostatic Diseases (2010) 13, 300–306

& 2010 Macmillan Publishers Limited All rights reserved 1365-7852/10

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REVIEW

Prostate cancer prevention: concepts and clinical recommendations

JL Silberstein and JK Parsons

Division of Urologic Oncology, UC San Diego Medical Center, Moores UCSD Comprehensive Cancer Center, VA San Diego Medical
Center, La Jolla, San Diego, CA, USA

Prevention is an important strategy for limiting prostate cancer morbidity and mortality. Two major
types of prevention are primary (reduction of incident cases) and tertiary (inhibition of disease
progression and recurrence). Pharmacological and dietary interventions have potential functions in
both the primary and tertiary prevention of prostate cancer. Five-a reductase inhibitors (5-ARIs)
reduce the incidence of prostate cancer in both general and higher-risk populations and are
currently under study for tertiary prevention in active surveillance and biochemical recurrence
patients. Selenium, vitamin E, and vitamin C do not prevent incident prostate cancer in the general
population; however, other promising diet-based interventions are currently under study for
tertiary prevention. We recommend consideration of 5-ARIs for prostate cancer prevention in
(1) asymptomatic men with a PSA p3.0 ng ml–1 who are undergoing or anticipate undergoing
PSA screening for early detection of prostate cancer and (2) asymptomatic men with PSA X2.5 and
p10 ng ml–1 and an earlier prostate biopsy negative for cancer. Men should be informed of the
potential risks of 5-ARI therapy. Currently, there is neither clinical evidence to support the use of
5-ARIs for tertiary prevention in active surveillance or biochemical recurrence populations, nor
micronutrients for prostate cancer prevention of any type.
Prostate Cancer and Prostatic Diseases (2010) 13, 300–306; doi:10.1038/pcan.2010.18; published online 22 June 2010

Keywords: prevention; chemoprevention; 5-ARI; PCPT; REDUCE

Introduction chemoprevention and suggests a set of practical

guidelines for the clinician to follow.
Prostate cancer chemoprevention
Prostate cancer, the most commonly diagnosed non-
cutaneous cancer among US men, represents an im-
General principles of disease prevention
portant target for disease prevention for several rea-
There are three basic types of prevention: primary,
sons.1,2 First, the majority of patients now present with
secondary, and tertiary (Figure 1). Primary focuses on
localized, low-risk cancers that are potentially amenable
prevention of incident disease in at-risk populations,
to prevention. Second, despite technological and techni-
secondary on attenuating the severity of prevalent
cal refinements, the most common therapies—surgery
disease through early detection and intervention, and
and radiation—are associated with substantial detri-
tertiary on halting disease progression and recurrence in
ments to quality of life that persist for years after
patients. All three types of prevention have prominent
treatment.3,4 Finally, recent data suggest that many low-
functions in the management of prostate cancer. How-
risk prostate cancers are over-treated: the European
ever, because secondary prevention involves population
randomized study of screening for prostate cancer study
screening with PSA rather than chemoprevention, this
observed that prevention of one prostate cancer death
review discusses only primary and tertiary prevention.
necessitated screening of 1068 men with PSA and
There are three broad categories of chemoprevention
definitive treatment of an additional 48 cases of prostate
for prostate cancer: hormonal, dietary, and anti-inflam-
cancer.5
matory. Most studies have focused on hormonal inter-
Cancer chemoprevention is the use of natural,
ventions, which manipulate sex steroid hormone
synthetic, or biologic substances to prevent or suppress
pathways, and dietary interventions, which alter the
the development of cancer. This review summarizes
balance of nutritional intake.
Level 1 evidence and ongoing trials of prostate cancer
Inflammation is believed to be an important compo-
nent in the genesis of prostate cancer.6 Aspirin,7 non-
steroidal anti-inflammatory medications8, and statins9
Correspondence: JK Parsons, c/o UCSD Division of Urology, 200 West
Arbor Drive #8897, San Diego, CA 92103-8897, USA.
have been hypothesized to reduce the incidence of
E-mail: leparker@ucsd.edu prostate cancer. However, although there are several
Received 22 February 2010; revised 6 April 2010; accepted 18 May preclinical and epidemiologic studies supporting a
2010; published online 22 June 2010 protective effective of anti-inflammatory therapies for

Figure 1 Concepts and randomized clinical trials of prostate
cancer prevention.
prostate cancer, as yet there have been no clinical
trials. Thus, anti-inflammatory medications will remain
beyond the scope of this review.
Risk stratification and defining the target population
In discussing prostate cancer prevention, it is important
to consider differential risks for incident, recurrent, and
progressive prostate cancer and to stratify men appro-
priately. These differences help define target populations
and are crucial to designing practical, realistic, and cost-
effective prevention strategies. For example, lower-risk
populations—in which the prevalence and incidence of
prostate cancer are relatively low, and thus the numbers
needed to treat to prevent a single case of prostate cancer
are relatively high—present particular challenges that
may not be present in higher-risk populations. On the
other hand, higher-risk populations may harbor a higher
prevalence of more aggressive phenotypes that are less
susceptible to prevention strategies.
Primary prevention
General population: the Prostate Cancer Prevention Trial,
Selenium and Vitamin E Cancer Prevention Trial, and
Physicians Health Study II studies
Several large randomized-clinical trials (RCTs) have
focused on primary prevention of prostate cancer in the
general population: men without prostate cancer who,
based on study selection criteria, were at relatively low
risk for prostate cancer diagnosis. The prostate cancer
prevention trial (PCPT) tested the hypothesis that
finasteride would prevent prostate cancer through
hormonal manipulation. Finasteride is a selective type
two five-a reductase inhibitor (5-ARI) that decreases
levels of circulating and intraprostatic dihydrotestosterone
Prostate cancer prevention
JL Silberstein and JK Parsons
(DHT) and is FDA approved for the treatment of 301
symptomatic BPH. Compared with testosterone, DHT
has a greater binding affinity for the androgen receptor
and results in 2- to 10-fold greater translational activity.10
Finasteride-induced reductions in DHT concentrations
result in decreased activation of the androgen receptor,
decreased prostate volume, and increased prostatic cell
apoptosis.11
In the PCPT, 18 882 men were randomized to receive
either finasteride or placebo over a 9-year period. Eligi-
bility criteria included age X55 years, PSA p3.0 ng ml–1,
and a normal digital rectal exam (DRE). Men underwent
annual screening with PSA and DRE: a PSA 44 ng ml–1
or abnormal DRE prompted biopsy. At study comple-
tion, all patients not earlier diagnosed with prostate
cancer underwent an end-of-study prostate biopsy.
The study ended 15 months before its intended comple-
tion date because of a significantly decreased incidence
of prostate cancer in patients taking finasteride.12 The
prevalence of prostate cancer was 18.4% for finasteride
versus 24.4% for placebo: a 25% decreased risk for
finasteride. Initially, it was reported that those in the
finasteride group with cancer had an increased prevalence
of higher-grade tumors (Gleason 46). Further analyzes of
the PCPT data, however, suggested that the increased
detection of high-grade tumors in the finasteride arm
resulted from diagnostic biases introduced by finasteride-
induced prostate volume reductions rather than alterations
in tumor characteristics.13 Men on finasteride experienced
significantly more loss of libido, gynocomastia, erectile
dysfunction, and reduced volume of ejaculate compared
with those on placebo,12 though the clinical significance of
these findings remains a matter of debate.14
The PCPT is an important study in that it showed a
significantly reduced risk in biopsy-diagnosed prostate
cancer in the treatment arm. Still, the clinical significance
of these findings has been questioned. It is estimated that
71 healthy men would need to be treated with finasteride
for 7 years to prevent one case of prostate cancer.15
Of note, the American Urologic Association and
the American Society of Clinical Oncology have
jointly released clinical practice guidelines on the use
of 5-ARIs for prostate cancer prevention. The guidelines
were based on a systematic, quantitative meta-analysis
of 15 randomized-controlled trials. They concluded
that asymptomatic men with PSA p3.0 ng ml–1 who
are undergoing screening for prostate cancer may benefit
from a discussion about the benefits and risks of
finasteride for prostate cancer prevention.15
The selenium and vitamin E cancer prevention trial
(SELECT) was a randomized, phase 3, placebo-controlled
study that was the largest cancer prevention trial ever
undertaken.16 Selenium is an essential trace nutrient that
human beings ingest through plant consumption. La-
boratory studies have indicated that it alters androgen
receptor signaling modulation, induces apoptosis, and
inhibits growth in prostate cancer cells.17,18 Numerous
epidemiological studies have observed reductions in
prostate cancer risk ranging from 26 to 52%, depending
on the population under study and the amount of
selenium ingested.19 Vitamin E is a collective term for
4 tocopherols and 4 tocotrienols. The main dietary
sources of vitamin E are vegetable oils and a-tocopherol,
which is found in dietary supplements and is thought to
be the most biologically active form20 Preclinical data
Prostate Cancer and Prostatic Diseases
 Prostate cancer prevention
JL Silberstein and JK Parsons
302 have suggested that vitamin E potentially inhibits
carcinogenic pathways in prostate cancer.21 In addition,
epidemiological data have shown significantly decreased
risk of incident or advanced prostate cancer with vitamin
E intake in the a-tocopherol, b-carotene trial,22 the Health
Professionals Follow-up study,23 the prostate, lung,
colorectal and ovarian cancer screening trial,24 and the
NIH-AARP diet and health study.25
The primary end point of SELECT was incident
prostate cancer. Secondary end points included overall
survival, cardiovascular events, and diabetes. Eligibility
criteria included age 450 years (African Americans)
or 455 years (all others), a serum PSA p4 ng ml–1, and
normal DRE findings. SELECT opened in 2001 and
finished accrual of 35 533 participants in 2004. Partici-
pants were randomized to selenium alone (200 mg per
day from L-selenomethionine), vitamin E alone (400 IU
per day of all-rac-a-tocopherol acetate), both, or placebo
for a minimum of 7 years.
Although the original study design planned for an
11-year duration, at the recommendation of an independent
data safety and monitoring committee, SELECT ended
4 years early because no evidence of benefit from vitamin E,
selenium, or the combination of the two was convincingly
demonstrated (Po0.0001), and there was no possibility of a
benefit with additional follow-up. Moreover, there were
non-significant increased risks of prostate cancer and
diabetes for vitamin E alone and selenium alone, respec-
tively. Compared with placebo, the hazard ratios for
prostate cancer were 1.13 (99% confidence interval [CI],
0.95–1.35; 95% CI, 0.99–1.29; P ¼ 0.06) in the vitamin E-only
group, 1.05 (99% CI, 0.88–1.25; 95% CI, 0.91–1.20; P ¼ 0.52)
in the selenium þ vitamin E group, and 1.04 (99% CI, 0.87–
1.24; 95% CI, 0.90–1.18; P ¼ 0.62) in the selenium-only group.
Similarly, the physicians health study II was a
randomized, phase 3, placebo-controlled trial of vitamins
C and E.26 Vitamin C (ascorbic acid) is a water-soluble
anti-oxidant and acts as a free-radical scavenger. Vitamin
C may potentially inhibit malignant transformation
through prevention of DNA adduct formation and
reduction of in vivo formation of carcinogenic N-nitroso
compounds.27,28 The primary outcome of physicians
health study II was incident prostate cancer. More than
14 000 male physicians X50 years were randomized to
vitamin E (400 IU synthetic a-tocopherol) every other
day, vitamin C (500 mg synthetic ascorbic acid) every
day, or placebo. Neither vitamin C nor vitamin E
supplementation reduced the risk of prostate or total
cancer over an 8-year study period.
The outcomes of physicians health study II and
SELECT have dampened enthusiasm for prostate cancer
prevention using micronutrient or vitamin supplements.
Potential explanations for the lack of efficacy of these
supplements include incorrect dosages, imperfect study
designs, flawed interpretations of earlier observational
evidence and—perhaps most importantly—absence of a
clinically significant physiological effect.
Men at higher risk for prostate cancer diagnosis: the
Reduction by Dutasteride of Prostate Cancer Event study
and toremifene
Despite the promising findings of the PCPT, null results
for primary prevention studies of micronutrients in men
Prostate Cancer and Prostatic Diseases
at relatively low risk of incident prostate cancer highlight
the potential pitfalls of prevention studies in populations
with a low prevalence of the disease of interest.
Other studies have targeted higher-risk populations.
The reduction by dutasteride of prostate cancer events
(REDUCE) trial was designed to determine whether
the 5-ARI dutasteride would reduce prostate cancer
incidence in higher-risk patients. There are two well-
characterized isoforms of 5-ARI.29,30 Type 1 is expressed
predominantly in extra-prostatic tissue, and its function
in human physiology remains to be defined. Type 2 is
expressed in high quantities in the prostate.31 A third
isoform has been described; its significance remains
unknown.32 Finasteride is a selective 5-ARI and blocks
only the 5-ARI isoform 2; dutasteride is non-selective
and blocks isoforms 1 and 2. Although type 2 is the
predominant form in the prostate, type 1 potentially
has a more substantial function in the development of
prostate cancer than was earlier thought.10,33–35 As dutas-
teride inhibits both isoforms, it results in greater
reductions in serum and intraprostatic DHT levels than
finasteride.36–39
REDUCE was a 4-year, multi-institutional, RCT of
0.5 mg daily oral dutasteride versus placebo in 8000 men.
Inclusion criteria included PSA 2.5–10 ng ml–1 for men
50–60 years or 3.0–10 ng ml–1 for men 60–75 years;
prostate volume o80 ml; American Urologic Association
symptom score o25; and a prostate biopsy negative
for cancer, high-grade prostatic intraepithelial neoplasia
(HGPIN), and atypical small acinar proliferation
within the earlier 6 months. Patients received PSA
screening every 6 months with 10 core prostate
biopsies for cause (at any time based on the clinical
judgment of the treating physician) and at years 2
and 4. Preliminary results indicated that dutasteride
resulted in a 23% reduced risk of biopsy-detectable
prostate cancer compared with placebo: 29% of patients
taking placebo were found to have prostate cancer
compared with 22.5% on dutasteride. Importantly,
the risk of developing high-grade tumors was similar
between groups.29,30
REDUCE has several important implications with
respect to the use of 5-ARIs to prevent prostate cancer.
First, it confirmed the findings of the PCPT: 5-ARIs can
reduce the risk of biopsy-detectable disease. Second,
it validated the post hoc PCPT analyzes showing that
5-ARI prophylaxis was not associated with increased
risk of high-grade disease. Third, it showed the validity
of using 5-ARI prophylaxis in a patient population at
higher risk of prostate cancer diagnosis.
Finally, one additional study of hormonal manipu-
lation in higher-risk populations deserves mention: an
RCT of the selective estrogen receptor modulator
toremifene in men with biopsy-proven HGPIN. Estradiol
is thought to contribute to the origination of HGPIN by
inducing hyperplasia and dysplasia, though the mechan-
ism has not been fully elucidated.40 Toremifene has
mixed estrogen agonist and antagonist activities and is
primarily used for the treatment and prevention of
estrogen receptor-positive breast cancer. HGPIN is
generally believed to be a precursor lesion to prostate
cancer, and it was originally thought that isolated
HGPIN on biopsy indicated an increased risk of prostate
cancer diagnosis on subsequent biopsy.41 More recent
studies have since refuted this principle.42,43

Five hundred and fourteen patients with biopsy-
proven HGPIN were randomized to 20, 40, or 60 mg
toremifene, or placebo. Prostate biopsies were repeated
at 6 months and 1 year. Although toremifene cohorts
showed potential efficacy at all three dosages, only those
in the 20 mg arm had a statistically significant decreased
risk of cancer on repeat biopsy compared with placebo
(24.4% versus 31.2%, Po0.05). There was no increased
risk of serious adverse events or thromboembolic events
in the toremifene cohorts. The authors estimated that
toremifene would prevent 6.8 cancers annually per 100
men treated with toremifene. Although it is unclear why
only the 20 mg arm showed a significant reduction in the
risk of prostate cancer, the authors hypothesize that it
was the greater selectivity and inhibition of the a subtype
of the estrogen receptor, which stimulates prostate
growth. Still, given current clinical recommendations
for HGPIN, toremifene should not be considered for
prostate cancer prevention at this time.42,44
Tertiary prevention
Tertiary prevention focuses on halting disease progres-
sion and recurrence in patients with prostate cancer.
The widespread use of PSA screening has led to a stage
migration in prostate cancer, with men being diagnosed
with low-pathologic and low-clinical stage disease
compared with historical cohorts.45 As a result, many
tumors that were not earlier detected are now being
diagnosed at early stages and are potentially amenable to
tertiary prevention. In addition, treatment with intent to
cure at younger ages allows for a longer window of time
for potential disease recurrence or progression during
a patient’s lifetime.
For these reasons, hormonal and dietary prevention
strategies are currently under study in prostate cancer
patients. Importantly, studies of tertiary prevention are
all ongoing: to date, there are no results from large RCTs on
which to base clinical recommendations.
Reduction by Dutasteride of Clinical Progression Events
in Expectant Management, Therapeutic Assessment of
Rising PSAs, Avodart after Radical Therapy for Prostate
Cancer and Men’s Eating And Living studies
Reduction by dutasteride of clinical progression events
in expectant management is an ongoing trial testing the
hypothesis that the 5-ARI dutasteride will prevent
disease progression in patients with low-risk prostate
cancer on active surveillance. Three hundred men aged
50–80 years with biopsy-proven clinical T1c or T2a
prostate cancer diagnosed within the earlier 6 months
were randomized to receive dutasteride 0.5 mg per day
or placebo for 3 years. At baseline, participants had
Gleason sum p6 disease and a serum PSA p10 ng ml–1.
Repeat biopsies will be performed at 1.5 and 3 years, and
PSA results will be provided to physicians and partici-
pants. The primary study end point is time to disease
progression (defined as time to treatment or pathologic
progression). Of note, these investigators hypothesize
that dutasteride may reduce anxiety of patients on active
surveillance by decreasing PSA and potentially dampen-
ing PSA spikes. Reduction by dutasteride of clinical
Prostate cancer prevention
JL Silberstein and JK Parsons
progression events in expectant management finished 303
accrual in 2007 and is expected to complete follow-up in
2010.46
Similarly, the avodart after radical therapy for prostate
cancer study is a 2-year RCT to test the hypothesis that
dutasteride will reduce disease progression in patients
with biochemical recurrence after primary treatment for
prostate cancer. Biochemical (PSA-only) recurrence after
radical prostatectomy or radiotherapy for localized
prostate cancer occurs in 27–53% of patients within
10 years.47 Biochemical recurrence predates clinically
detectable metastatic disease by an average of 8 years.48
In 1995, Andriole et al.49 reported that men with
detectable PSA after radical prostatectomy treated with
finasteride experienced delay in the rise of serum PSA
and reduction in local and distant recurrences compared
with a placebo cohort. It is hypothesized that dutasteride
may be used for tertiary prevention of progression from
PSA-detectable disease only after primary treatment to
clinically detectable metastatic disease and thus prevent
or delay the need for second-line treatment.50
Avodart after radical therapy for prostate cancer study
is an ongoing European trial in which patients were
initially treated for prostate cancer with intent to cure
and subsequently experienced biochemical recurrence.
Participants are stratified by earlier therapy and rando-
mized to dutasteride daily or placebo. Patients who
underwent earlier radical prostatectomy must experience
three PSA rises from nadir, with each being X4 weeks
apart, and a PSA between 0.4 and 10 ng ml–1 at
enrollment. Patients who underwent earlier radiation
therapy must wait at least 1 year from end of radio-
therapy and then must have three increases in PSA from
nadir, with each rise X4 weeks apart and an enrollment
PSA of 2–20 ng ml–1. Exclusion criteria include men with
rapid (o3 months) or prolonged (424 months) PSA
doubling time. It is estimated that 276 patients will
enroll. Study end points include time to PSA doubling,
time to disease progression, treatment response (PSA
decrease or increase of 15% from baseline), changes in
PSA and PSA doubling time, and changes in anxiety.
PSA will be measured every 3 months and patients with
evidence or signs of disease progression will be offered
alternative treatment strategies. The results from this
study are likely to be unavailable for several years.
The therapeutic assessment of rising PSAs study is an
ongoing RCT designed to determine the impact of
dutasteride on patients with castrate-resistant prostate
cancer on bicalutamide.51 The rationale behind this
study is that low levels of circulating testosterone may
still be converted to DHT by 5-a reductase, and this DHT
has a greater affinity for the androgen receptor than
bicalutamide. Thus, more complete blockage of the
androgen receptor will theoretically be achieved if it is
blocked directly with bicalutamide and concurrently
intraprostatic DHT levels are suppressed with dutaste-
ride. Approximately 150 subjects with PSA progression
despite androgen deprivation therapy, with PSA bet-
ween 2 and 20 ng ml–1 and serum testosterone o50 ng
per 100 ml, and who have a negative bone scan within
8 weeks of enrollment and anticipated 42-year survival,
are randomized to bicalutamide 50 mg once daily and
either dutasteride 3.5 mg daily or placebo.
Finally, the men’s eating and living study is a multi-
center, 5-year, National Cancer Institute-funded RCT
Prostate Cancer and Prostatic Diseases
 Prostate cancer prevention
JL Silberstein and JK Parsons
304 expected to open for accrual in 2010 through Cancer and
Leukemia Group B. The first national trial of diet change
for prostate cancer, men’s eating and living will test the
hypothesis that a dietary intervention consisting of high
vegetable intake (primarily tomatoes, carotenoids, and
crucifers) will decrease disease progression in patients
with low-risk prostate cancer on active surveillance.
Robust preclinical and epidemiological evidence suggest
that diet may alter prostate cancer initiation and
progression. Macronutrients and micronutrients asso-
ciated with decreased prostate cancer risk include
carotenoids (particularly lycopene), cruciferous vegeta-
bles, dietary fat, soy products, and omega fatty acids.52
A range of phytochemicals in fruits and vegetables
could have effects on a metabolically active organ such as
the prostate, and a number of plausible mechanisms
have been proposed.53
Men’s eating and living will recruit 440 participants
with biopsy-proven prostate cancer, clinical stage pT2a
diagnosed within the earlier 24 months with p2 tissue
cores positive for cancer, p50% of any one core positive
for cancer, Gleason sum p6 (men p70 years) or biopsy
Gleason score p(3 þ 4) ¼ 7 (men 470 years), and PSA
p10 ng ml–1. The intervention will consist of centralized,
telephone-based diet counseling that was earlier
shown in a pilot study to be highly effective at changing
dietary habits of prostate cancer patients.54,55 The
primary outcome variable will be disease progression
as determined by PSA and pathology on repeat
biopsy; secondary outcome variables will include
incidence of active treatment, quality of life, and anxiety
related to prostate cancer. The results are not expected
before 2015.
Prostate cancer prevention: challenges and opportunities
As these agents diffuse into clinical practice, several
issues remain unresolved. First, the economic costs of
adopting a widespread prevention strategy remain
undefined. Analyzes of PCPT and surveillance, epide-
miology, and end results data show that, in terms of
dollars per life year saved, finasteride is not a cost-
effective strategy for prostate cancer prevention in a
population of lower-risk men.56,57 Further study, includ-
ing the potential for 5-ARIs to prevent incident BPH,
is required.
Second, although a preponderance of clinical evidence
currently supports the interpretation that 5-ARIs do not
increase the risk of high-grade disease or produce other
serious side effects, the potential repercussions of chronic
administration, spanning decades, remain unknown. It is
also not known how discontinuation of 5-ARIs after
many years may influence cancer biology or prostate
physiology.
Third, since the target population comprises many
millions of men, it is unclear who should lead the
development and application of prevention strategies.
Any successful implementation of a prostate cancer
prevention program will likely necessitate a coordinated
partnership of multiple disciplines including urology,
primary care, epidemiology, and health policy. Still,
although many questions remain unanswered, the
potential for these agents to attenuate the population
effects of prostate cancer represents a tremendous
opportunity to serve the public health.
Prostate Cancer and Prostatic Diseases
Prostate cancer prevention: clinical recommendations
In summary, based on available evidence and published
clinical guidelines, we recommend the following:
1. 5-ARIs should be considered for prostate cancer preven-
tion in: (1) asymptomatic men with a PSA p3.0 ng ml–1
who are undergoing or anticipate undergoing PSA
screening for early detection of prostate cancer and
(2) asymptomatic men with PSA X2.5 and p10 ng ml–1
and an earlier prostate biopsy negative for cancer.
2. There is no definitive clinical evidence to support the
use of 5-ARIs to inhibit cancer progression in active
surveillance or biochemical recurrence patients, or to
increase the sensitivity of DRE, PSA, and prostate
biopsy for detecting progression in active surveillance
patients. 5-ARIs may be considered in active surveil-
lance patients for the treatment of BPH/lower urinary
tract symptoms.
3. Men should be informed of the potential risks of
5-ARIs, although studies to date indicate that the risk
of high-grade cancer is unverified.
4. Owing to the lack of efficacy and the potential for
harmful side effects, micronutrients—including sele-
nium, vitamin E, and vitamin C—should not be used
for prostate cancer prevention at this time.
Conflict of interest
The authors declare no conflict of interest.
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