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Chemoprevention strategies in prostate cancer

Author: A Oliver Sartor, MD
Section Editors: Nicholas Vogelzang, MD, W Robert Lee, MD, MS, MEd, Jerome P Richie, MD, FACS
Deputy Editor: Diane MF Savarese, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2019. | This topic last updated: Jan 14, 2019.

INTRODUCTION

Prostate cancer is the second most common cancer in men worldwide, with over 1.2 million new
cases and 358,000 deaths annually, according to data from the GLOBOCAN database. In the United
States, there will be an estimated 175,000 cases and 31,620 deaths from prostate cancer in 2019 [1].

In the United States, the incidence of prostate cancer detection dramatically rose in the early 1990s in
conjunction with the increasing utilization of prostate-specific antigen (PSA) screening. After an initial
peak, incidence rates fell, but they have persisted at a rate nearly twice that recorded in the pre-PSA
era, suggesting that many cases are clinically indolent and would never have become clinically
apparent. Despite the increase in diagnosis of early stage prostate cancer, the impact of earlier
treatment on survival remains to be proven.

The implementation of the United States Preventative Services Task Force (USPSTF) guidelines
assigning a recommendation level of D has reduced the number of men seeking early detection, as
well as reduced the number of transrectal ultrasound (TRUS) biopsies. Some centers have reported
an increase in men with more aggressive and advanced disease.

The high incidence of prostate cancer, its associated morbidity and mortality, the complications
associated with its treatment, and a partial understanding of its biologic basis have led to a focus on
chemoprevention strategies. The most extensive data come from the use of 5-alpha reductase (5-AR)
inhibitors; other classes of agents are also being explored.

The rationale for chemoprevention, the results with 5-AR inhibitors, and the more limited data with
other approaches are presented here. Screening for prostate cancer, an alternative approach that
focuses on early detection to decrease morbidity and mortality, is discussed elsewhere. (See
"Screening for prostate cancer".)

RATIONALE

Three factors have contributed to the rationale for prostate cancer chemoprevention in men: the long
latency period between the initial evidence of prostate cancer and the development of overt or fatal
disease, the androgen dependency of these tumors, and the availability of intermediate endpoints for
use in clinical trials.

Long latency period — The marked discrepancy between the autopsy prevalence of occult prostate
cancer and the incidence of clinically manifest disease indicates that there is a long latency phase
and significant heterogeneity in the rate of progression of early neoplastic lesions. Progression to
invasive cancer in men with high-grade prostatic intraepithelial neoplasia (PIN) may take 10 years or
more. (See "Precancerous lesions of the prostate: Pathology and clinical implications", section on
'Prostatic intraepithelial neoplasia'.)

As a result, chemoprevention strategies that do not reverse the premalignant condition but merely
delay its progression to invasive cancer may be sufficient to improve survival or avoid the
complications of the disease or its treatment [2,3].

Androgen dependency — Direct or indirect androgenic influences are important in the malignant
transformation of prostatic tissue. Men with 5-alpha reductase (5-AR) deficiency (the enzyme that
converts testosterone to dihydrotestosterone [DHT], the most active androgen in the prostate) do not
develop prostate cancer [4]. The precursor lesion, high-grade PIN, is also hormonally dependent. The
atrophy and apoptotic changes that occur with androgen deprivation in normal and hyperplastic
prostatic epithelium and in invasive cancers are also observed in PIN [5].

These data suggest that interference with normal androgen balance may affect prostate cancer
incidence. Medical therapies directed at hormonal manipulation include estrogens, antiandrogens,
gonadotropin-releasing hormone (GnRH) agonists, and 5-AR inhibitors. Most of these therapies are
not candidates for use as chemopreventive agents because of potential side effects. The use of 5-AR
inhibitors or antiandrogens that block the androgen receptor may be associated with fewer side
effects because serum testosterone levels remain unaltered. (See "Side effects of androgen
deprivation therapy".)

Clinical trials biomarkers — Development of chemopreventive agent(s) may be facilitated by the

availability of biomarkers that may predict the subsequent development of prostate cancer or that can
be used to define its progression and, thus, serve as intermediate endpoints for clinical trials.
 ● PIN – PIN represents a spectrum of dysplastic changes that are limited to prostatic acini and do
not invade the basement membrane. High-grade PIN is thought to be associated with an
increased prostate cancer risk. The pathologic features of PIN and its relationship to cancer are
discussed separately. (See "Precancerous lesions of the prostate: Pathology and clinical
implications", section on 'Prostatic intraepithelial neoplasia'.)

● Prostate-specific antigen (PSA) – Changes in serum PSA concentration and its association with
prostate cancer suggest that serum PSA may be a useful biomarker and that defined changes
could act as intermediate endpoints in the setting of chemoprevention trials. However, serum
PSA is also secreted by normal prostate tissue, and as an androgen-regulated gene, levels are
incompletely correlated with tumor burden. (See "Measurement of prostate-specific antigen".)

5-ALPHA REDUCTASE INHIBITORS

The 5-alpha reductase (5-AR) inhibitors finasteride and dutasteride are used primarily for treatment of
benign prostatic hyperplasia. They improve lower urinary tract symptoms by blocking the conversion
of testosterone into the more potent androgen dihydrotestosterone (DHT). (See "Medical treatment of
benign prostatic hyperplasia", section on '5-alpha-reductase inhibitors'.)

Androgens are a key driver of prostate carcinogenesis. There are data from at least two randomized
trials that support a reduced risk of prostate cancer in men receiving 5-AR inhibitors; however, no
survival benefit has been shown in either trial, and both raised concerns about a possible increased
risk of high-grade prostate cancer. The US Food and Drug Administration (FDA) has not approved the
use of these agents for prostate cancer prevention, and in 2011, it issued a safety warning about the
elevated risk of high-grade cancers, stating that one additional high-grade cancer would occur for
every three to four lower grade cancers that would be prevented [6]. Although a subsequent analysis
of data from the Prostate Cancer Prevention Trial (PCPT) found that finasteride increased the
detection rate of high-grade prostate cancer by shrinking the prostate, thereby introducing a potential
detection bias [7], and the clinical significance of this finding remains unclear, concerns remain, and
these drugs are not widely used for prostate cancer chemoprevention.

For most men, we suggest not using chemopreventive therapy with a 5-AR inhibitor. However,
chemopreventive therapy with a 5-AR inhibitor in conjunction with monitoring serum prostate-specific
antigen (PSA) may be appropriate for those who place a higher value on preventing cancer than on
the side effects associated with such therapy and the uncertainties as to benefits and risks.

Guidelines from an expert panel of the American Society of Clinical Oncology (ASCO) and the
American Urological Association (AUA) identified key issues that clinicians and men should discuss
when deciding whether or not to use a 5-AR inhibitor for prostate cancer chemoprevention [8,9].
These include the following:

● 5-AR inhibitors decrease, but do not eliminate, the risk of prostate cancer.

● An elevated rate of high-grade prostate cancers has been observed in patients taking finasteride
[10] and dutasteride [11], although the significance of this observation remains unclear.

● There is no information about whether these agents decrease the risk of death from prostate
cancer or affect overall survival. There is also no information about the effects of their use
beyond seven years.

● Side effects of these agents include gynecomastia, decreased libido, erectile dysfunction, and
decreased ejaculate volume. At the same time, these agents may decrease urinary tract
symptoms due to benign prostatic hyperplasia.

● 5-AR inhibitors reduce serum PSA levels by an average of 50 percent, which can affect the use
of serum PSA for prostate cancer detection in men treated with these agents [12-14].

Finasteride: PCPT — In the Prostate Cancer Prevention Trial (PCPT), 18,882 men were randomly
assigned to finasteride (5 mg/day) or placebo between 1994 and 1997 [10,15].

Men were considered at elevated risk of prostate cancer based upon age ≥55 years, African-
American ethnicity, or having a first-degree relative with prostate cancer. All had a normal digital
rectal examination (DRE) and a serum PSA ≤3 ng/mL.

Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride
(which decreases the serum PSA by approximately 50 percent), was ≥4 ng/dL or if the DRE became
abnormal. In addition, all men were offered a prostate biopsy at the end of study (seven years).

The PCPT was closed early because the primary study endpoint (ie, a decrease in the prevalence of
biopsy-proven prostate cancer in the finasteride population compared with placebo) was met. The
initial analysis found a 25 percent decrease in the incidence of prostate cancer with seven years of
finasteride, but there was also an observed increase in the absolute number and proportion of high-
grade prostate cancers (ie, Gleason score ≥7) [10].

A long-term follow-up of this study (up to 18 years of follow-up), which included the identification of
187 additional cases of prostate cancer, analyzed overall survival data through October 2011 [15]:

● There was a statistically significant decrease in the incidence of prostate cancer in men assigned
to finasteride compared with placebo (10.5 versus 14.9 percent, relative risk [RR] 0.70, 95% CI
0.65-0.76).
 ● There remained a small but statistically significant increase in the risk of high-grade prostate
cancer (Gleason score ≥7) with finasteride (3.5 versus 3.0 percent, RR 1.17, 95% CI 1.00-1.37, p
= 0.05).

● The 15-year overall survival rates for the finasteride and placebo groups were 78.0 and 78.2
percent, respectively (unadjusted hazard ratio [HR] 1.02, 95% CI 0.97-1.08).

● Among men who subsequently developed prostate cancer, there were no significant differences
in the 10-year overall survival rates in men assigned to finasteride or placebo. For men with low-
grade prostate cancer (Gleason score ≤6), the 10-year overall survival rates were 83.0 and 80.9
percent, respectively, and for those with high-grade prostate cancer (Gleason score ≥7), the 10-
year overall survival rates were 73.0 and 73.6 percent, respectively.

Long-term benefit after discontinuation of finasteride was also explored in a subsequent analysis
linking PCPT clinical records to the participants' Medicare claims data [16]. Throughout the entire
course of follow-up (median 16 years), finasteride participants maintained a 21 percent reduction in
the risk of prostate cancer (HR 0.79, 95% CI 0.74-0.84). However, the protective effect was significant
only through year 7.5 (HR 0.71, 95% CI 0.66-0.77) and not afterwards (HR 1.10, 95% CI 0.96-1.26).

The observed increase in the number of patients with high-grade cancers dampened enthusiasm for
the use of finasteride as a chemopreventive agent [17], even though several subsequent analyses
suggested that the observed increase in high-grade lesions did not represent a true alteration in the
biology of the disease and, instead, likely indicated detection bias attributed to the fact that finasteride
shrinks the prostate, thereby increasing the detection of high-grade disease [18-22].

The absence of a difference in overall survival with longer follow-up provides evidence that an
increase in high-grade prostate cancer is not a major factor affecting overall survival and that
chemoprevention may safely decrease the incidence of low-grade prostate cancers [15]. However,
this secondary analysis was not able to provide any data on prostate cancer-specific mortality or
morbidity associated with high-grade lesions. Furthermore, treatment with finasteride in this protocol
was conducted with regular monitoring of serum PSA, which might not be a component of patient
management outside a protocol setting.

Dutasteride: REDUCE trial — The effects of dutasteride on the incidence of prostate cancer were
evaluated in the double-blind Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, in
which 8336 men were randomly assigned to dutasteride (0.5 mg/day for four years) or placebo [11].
All men were considered at increased risk for prostate cancer based upon age and serum PSA level,
and all had a single negative prostate biopsy within six months prior to protocol entry. Men 50 to less
than 60 years of age had a baseline serum PSA of 2.5 to 10 ng/mL, while those 60 to 75 years of age
had a PSA 3 to 10 ng/mL. The protocol called for repeat 10-core biopsies at two and four years after
treatment initiation.

Key findings included:

● The incidence of prostate cancer was significantly reduced in men assigned to dutasteride
compared with placebo (25.1 versus 19.9 percent, RR reduction 23 percent).

● The decrease in incidence was limited to cancers with a Gleason score of 5 or 6, which
constituted 70 percent of all cases diagnosed. There was no statistically significant reduction in
risk of prostate cancer with Gleason scores of 7 to 10. Overall, in years 1 through 4, there were
220 Gleason score 7 to 10 tumors diagnosed in the dutasteride group and 233 in the placebo
group, a difference that was not significant (6.7 versus 6.8 percent, p = 0.81). Mortality rates
were similar in both groups, and no deaths were attributed to prostate cancer in either group.

Other data — Additional data on the impact of 5-AR inhibitors on the risk of prostate cancer are
available from a Swedish population-based cohort study of all men over the age of 40 who had at
least one PSA test in Stockholm County between 2007 and 2015 [23]. Of the 333,820 men in the
cohort, 23,442 had been prescribed a 5-AR inhibitor at some time during the study period. Treatment
with a 5-AR inhibitor decreased the risk of prostate cancer, and the effect was larger with longer
duration of exposure (0.1 to 2 years, HR 0.81, 95% CI 0.71-0.93; two to four years, HR 0.39, 95% CI
0.32-0.47; four to six years, HR 0.40, 95% CI 0.31-0.52; and six to eight years, HR 0.31, 95% CI
0.16-0.60). The use of a 5-AR inhibitor reduced the risk of prostate cancer with a Gleason score of 6
to 7, but it had no impact on the risk of higher grade (Gleason score 8 to 10) disease. However,
among the men with the shortest exposure to a 5-AR inhibitor, there was a 56 percent increase in the
risk of high-grade disease, a similar observation as in the PCPT. This observation is consistent with
detection bias, as described above, as it was not seen in men who had longer exposures to the 5-AR
inhibitor. (See 'Finasteride: PCPT' above.)

These data provide some reassurance that treatment with a 5-AR inhibitor for lower urinary tract
symptoms in men is safe with regard to prostate cancer risk, but long-term follow-up of phase III
clinical trials demonstrating improved survival is needed to confirm the true impact of 5-AR inhibitors
as chemopreventive agents. (See "Medical treatment of benign prostatic hyperplasia", section on '5-
alpha-reductase inhibitors'.)

OTHER AGENTS

A number of other agents are being studied to prevent prostate cancer. All of them remain
experimental.
Statins — Multiple studies have looked at the relationship between statin use and prostate cancer.
Although the data regarding an impact on the incidence are equivocal, epidemiologic findings suggest
that statin use may have a beneficial effect on the risk of prostate cancer progression and death.
Prospective trials are needed to validate the importance of these agents. (See "Investigational
approaches for the treatment of advanced prostate cancer", section on 'Statins'.)

Metformin — Epidemiologic studies have suggested that diabetic patients using metformin have a
decreased incidence of a variety of malignancies other than prostate cancer compared with those not
being treated with metformin. No prospective trials support these observations, and caution is
advised. (See "Cancer prevention", section on 'Metformin'.)

Metformin does not appear to have a substantial impact on the overall incidence of prostate cancer.
As an example, in a study of over 119,000 men ≥66 years old with incident diabetes, prostate cancer
was subsequently diagnosed in 5306 [24]. There was no difference in the risk of prostate cancer
(adjusted odds ratio [OR] 1.03, 95% CI 0.96-1.1).

Metformin may have an effect on the progression of disease in diabetic patients with prostate cancer.
In a study that included 3837 patients older than 66 years with a new diagnosis of diabetes who were
subsequently diagnosed with prostate cancer, prostate cancer-specific mortality was significantly
decreased in those treated with metformin [25]. The decrease in mortality with metformin use was
proportional to the cumulative duration of metformin use (hazard ratio [HR] for prostate cancer-
specific mortality 0.76 for each additional six months of use of metformin). This effect was not
observed with other diabetic medications. These observations require confirmation.

Vitamins and micronutrients — The available data on vitamins and dietary supplements for
chemoprevention are extensive and difficult to interpret. Currently, available data have not established
a role for any of these agents in the prevention of prostate cancer.

The most extensively studied agents are vitamin E (alpha-tocopherol) and selenium.

Vitamin E — Men should avoid vitamin E supplementation at doses that exceed dietary intakes.
Current evidence does not support a role for vitamin E supplementation in the prevention or treatment
of cancers, cardiovascular disease, dementia, or infection. (See "Vitamin supplementation in disease
prevention", section on 'Vitamin E' and "Overview of vitamin E".)

Two randomized trials, the alpha-tocopherol beta-carotene (ATBC) intervention trial [26-28] and the
Heart Outcomes Prevention Evaluation – The Ongoing Outcomes (HOPE-TOO) trial [29], provided
conflicting evidence regarding the incidence of prostate cancer as a secondary outcome.

Two randomized trials specifically designed to study the impact of vitamin E on prostate cancer
incidence failed to provide any evidence supporting a chemopreventive role:
 ● The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was designed to study the role
of selenium and vitamin E as agents to decrease the incidence of prostate cancer. In this trial,
35,533 men were randomly assigned to selenium (200 mcg/day), vitamin E (400 international
units/day), both, or neither with appropriate placebos [30]. This trial was stopped in October 2008
after an independent data safety monitoring committee found no evidence of a decrease in the
incidence of prostate cancer. Dietary supplementation with vitamin E significantly increased the
incidence of prostate cancer, and there were nonsignificant increases with selenium and the
combination of vitamin E plus selenium compared with placebo (HR for developing prostate
cancer 1.17, 1.09, and 1.05, respectively) [31,32].

● The Physicians' Health Study II (PHS II) was a double-blind, placebo-controlled trial in which
14,641 male clinicians ages 55 years and older were randomly assigned to beta-carotene,
vitamin E, ascorbic acid, and/or a multivitamin [33]. One of the primary endpoints of this study
was the prevention of prostate cancer. The incidence of prostate cancer was not significantly
reduced with any of the agents, including vitamin E (HR 0.97, 95% CI 0.85-1.09) [34].

Selenium — The relationship between prostate cancer and selenium intake and level is complex.
However, there is no evidence supporting a chemopreventive effect from selenium supplementation
[32]. (See "Risk factors for prostate cancer", section on 'Selenium and vitamin E'.)

The effect of selenium supplementation was directly evaluated in SELECT, which included 35,533
men at risk for prostate cancer. The incidence of prostate cancer was nonsignificantly increased with
selenium alone or in combination with vitamin E (HR 1.09 and 1.05, respectively). Further subsequent
analyses found that selenium supplementation did not benefit men with low selenium status but
increased the risk of high-grade prostate cancer among men with high selenium status [35].

Vitamin D analogs — A link between vitamin D levels and prostate cancer risk has been
suggested, mainly based upon the association of vitamin D deficiency with epidemiologic risk factors
such as age, African-American race, and geographic area of residence [36-43]. Preclinical studies
support an antiproliferative, antimetastatic, and differentiating effect of vitamin D and its analogues in
prostate cancer, providing a rationale for the consideration of these compounds as potential
chemopreventive agents. No prospective trials have confirmed this effect.

Retinoids — Retinoids are metabolites and analogs of vitamin A that are required for the proper
differentiation of various epithelial tissues, and they play a regulatory role in the activation of
cytokines and the extracellular matrix. Chemoprevention trials are ongoing with retinoids in lung
cancer, breast cancer, and head and neck cancer. (See "Chemoprevention and screening in oral
dysplasia and squamous cell head and neck cancer".)
Fenretinide, a synthetic retinoid, has been evaluated in men with prostate cancer in preliminary
studies [44-46]. However, these trials have not yielded evidence of activity, and this class of agents is
not under active investigation for chemoprevention against prostate cancer.

Dietary factors — A number of dietary factors have been analyzed for their association with the risk
of prostate cancer. Although information from these studies may be useful in defining new
approaches to chemoprevention, none of these has an established role in prostate cancer
chemoprevention. (See "Risk factors for prostate cancer", section on 'Diet'.)

Phytoestrogens (flavones, isoflavones, lignans) are naturally occurring plant compounds that have
estrogen-like activity. Genistein and daidzein, the predominant isoflavones in human nutrition, are
derived mainly from soybeans and other legumes.

Phytoestrogens may reduce prostate cancer risk either via their inherent estrogenic properties (which
favorably alter the hormonal milieu) or by inhibition of 5-alpha reductase (5-AR), which decreases
concentrations of the more prostate-active androgen dihydrotestosterone (DHT). The higher intake of
soy products among Asian men has been hypothesized to be one reason for the lower incidence of
prostate cancer among these men.

The most provocative data linking soy or phytoestrogen exposure to a reduced prostate cancer risk
come from animal studies [47-49]. In humans, most of the case-control studies have shown a modest
protective benefit of soy on prostate cancer risk. (See "Risk factors for prostate cancer", section on
'Soy intake'.)

In one randomized trial, 310 men with high-grade prostatic intraepithelial neoplasia were randomly
assigned to a combination of vitamin E, soy, and selenium or to placebo. There was no evidence that
the combination prevented progression to prostate cancer [50]. Several other randomized, placebo-
controlled clinical trials evaluating soy protein in men with treated prostate cancer who are at high risk
for recurrence are ongoing.

LIFESTYLE FACTORS

Potentially modifiable lifestyle factors, particularly smoking and obesity, have been shown to increase
the risk of prostate cancer, particularly for aggressive or advanced disease [51]. Factors such as diet
that are associated with good cardiovascular health may also contribute to preventing the initiation
and progression of prostate cancer. (See "Risk factors for prostate cancer", section on 'Cigarette
smoking' and "Risk factors for prostate cancer", section on 'Obesity' and "Healthy diet in adults".)
SUMMARY AND RECOMMENDATIONS

● The high incidence of prostate cancer, its associated morbidity and mortality, and its hormone
dependency all have made prostate cancer an important target for chemopreventive strategies.
(See 'Rationale' above.)

● In randomized trials, 5-alpha-reductase (5-AR) inhibitors have been shown to significantly

decrease the incidence of prostate cancer. However, no trials have demonstrated an impact on
prostate cancer mortality, and the possibility that these agents increase the incidence of high-
grade lesions cannot be excluded. (See '5-Alpha reductase inhibitors' above.)

The potential side effects (gynecomastia, decreased libido, erectile dysfunction), benefits
(decreased symptoms from benign prostatic hyperplasia), and areas of uncertainty (possible
increase in high-grade prostate cancer, long-term side effects) should be explained to men
considering chemopreventive therapy. For most men, we suggest not using chemopreventive
therapy with a 5-AR inhibitor (Grade 2B). However, chemopreventive therapy with a 5-AR
inhibitor in conjunction with monitoring serum prostate-specific antigen (PSA) may be appropriate
for those who consider preventing cancer more important than the side effects and uncertainties
associated with such therapy. (See '5-Alpha reductase inhibitors' above.)

There are no data that support the use of vitamin E, selenium, or other agents for routine use, and
such agents remain experimental. (See 'Other agents' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge E David Crawford, MD, who contributed to
an earlier version of this topic review.

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Topic 6949 Version 32.0

Contributor Disclosures
 A Oliver Sartor, MD Grant/Research/Clinical Trial Support: AstraZeneca [Prostate cancer (Olaparib and
durvealunab)]; Bayer [Prostate cancer (Radium-223)]; Constellation [Prostate cancer (CPI-1205)]; Dendreon
[Prostate cancer (Sipuleucel-T)]; Endocyte [Prostate cancer (PSMA Lu-177)]; Innocrin [Prostate cancer (VT464)];
Invitae [Prostate cancer (Germline genetic testing)]; Johnson & Johnson [Prostate cancer (Abiraterone,
apalutamide, niraparib)]; Merck [Prostate cancer (Pembro lizumab)]; Progenics [Prostate cancer (PSMA-LU-
177)]; Roche [Prostate cancer (Atezolizumab)]; Sanofi [Prostate cancer (Cabazitaxel)]; SOTIO [Prostate cancer
(DCVAC)]. Consultant/Advisory Boards: Advanced Accelerator Applications (AAA) [Prostate cancer (PSMA LU-
177)]; Astellas [Prostate cancer (Enzalutamide)]; AstraZeneca [Prostate cancer (Olaparib and durvealunab)];
Bayer [Prostate cancer (Radium-223)]; Blue Earth Diagnostics, Inc [Prostate cancer (Axumin)]; Constellation
[Prostate cancer (CPI-1205)]; Dendreon [Prostate cancer (Sipuleucel-T)]; EMD Serono [Prostate cancer
(Avelumab)]; Endocyte [Prostate cancer (PSMA LU-177)]; Hinova [Prostate cancer (HC-1119)]; Johnson &
Johnson [Prostate cancer (Abiraterone, apalutamide, niraparib)]; Myovant [Prostate cancer (Relugolix)]; Pfizer
[Prostate cancer (Enzalutamide)]; Progenics [Prostate cancer (PSMA-LU-177)]; Sanofi [Prostate cancer
(Cabazitaxel)]; NRG Oncology [Genitourinary cancer (Co-chairman of genitourinary cancer committee)]. Other
Financial Interest: Sanofi [Prostate cancer (Cabazitaxel, expert testimony)]. Nicholas Vogelzang, MD Speaker's
Bureau: Bayer [Prostate cancer (Radium 223)]; Sanofi [Prostate cancer (Cabazitaxel)]; Genentech/Roche
[Bladder cancer (Atezolizumab)]; Caris [Genetic profiling company]; AstraZeneca [Prostate cancer, lung and
bladder cancer (Zoladex, Durvalumab)]; Astellas [Prostate cancer (Enzalutamide)]. Consultant/Advisory Boards:
Bayer [Prostate cancer (Radium 223)]; Pfizer [Kidney cancer (Sunitinib, axitinib, avelumab), prostate cancer
(Enzalutamide), lung cancer (Crizotinib), Merkel cell cancer (Avelumab)]; Novartis [Kidney cancer, PNET
(Pazopanib, everolimus)]; Sanofi [Prostate cancer (Cabazitaxel)]; BMS [Kidney cancer (BMS-nivolumab)];
Genentech/Roche (Bladder cancer (Atezolizumab)]; Astra Zeneca [Bladder cancer (Durvalumab)]; Exelexis
[Kidney cancer (Cabozantinib)]; Clinical Care Options,; Dava Oncology/PER; Dendreon; Medivation/Astellas
[Prostate cancer (Enzalutamide)]; Janssen [Prostate cancer (Abiraterone, apalutamide)]; Heron [Nausea control
(Liposomal granisetron)]; Eisai [Kidney cancer (Levantinib)]; Boehringer Ingelheim [Mesothelioma (Nintedinib)];
Merck [Transitional cell cancer, lung cancer (Pembrolizumab); Dr Reddy's [Prostate cancer (Abiraterone)]; Tolero
[General oncology (New targeted agents)]; Fujifilm [General oncology (New cancer agents)]; Clovis [PARP
inhibitor-Rucaparib; Ovarian, breast and prostate cancer drug]. Employment: US Oncology [GU research
(None)]. Equity Ownership/Stock Options: Caris [Genetic testing for cancer (None)]. Other Financial Interest:
Novartis [Legal defense of everolimus patent]. W Robert Lee, MD, MS, MEd Equity Ownership/Stock Options:
Augmenix Inc [Prostate cancer (SpaceOAR)]. Jerome P Richie, MD, FACS Nothing to disclose Diane MF
Savarese, MD Nothing to disclose

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