Prevention of Prostate Cancer Bertrand Tombal, President of the European Organisation for Research and Treatment of Cancer (EORTC)

1. Prevention of Prostate Cancer.
An utopia ?
President
European Organisation for Research and Treatment of Cancer (EORTC)
Brussels, BE
Chairman Urology
Cliniques universitaires Saint Luc,
Brussels, BE

2. The goal.
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 Primary prevention aims to prevent disease or
injury before it ever occurs.
 e.g. education about healthy and safe habits
 drugs
 Secondary prevention aims to reduce the impact
of a disease or injury that has already occurred.
 e.g. personal strategies to prevent recurrence, or
implementation of programs to return people to
their original health and function to prevent long-
term problems.
 Tertiary prevention aims to soften the impact of
an ongoing illness or injury that has lasting
effects.
 rehabilitation programs, chronic disease
management programs
 support groups that allow members to share
strategies for living well

3. The Magic Pill doesn’t exist; why have we failed ?
 Unselected population.
 Naïve assumptions on the role of hormones, diet, and
lifestyle.
 Pill approach, versus education and precision
approaches.
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4. The Magic Pill doesn’t exist; why have we failed ?
Hormonal prevention: the dutasteride trial,
 Crude rate absolute risk reduction of Pca: 5.1% at 4 years,
But
 No difference in PCa or overall mortality
 No reduction in the risk of aggressive cancers (i.e., Gleason 7–10)
But
 decreased libido (3.3% vs. 1.6%); loss of libido (1.9% vs. 1.3%);
decreased semen volume (1.4% vs. 0.2%); erectile dysfunction
(9.0% vs. 5.7%); gynecomastia (1.9% vs. 1.0%).
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5. The Magic Pill doesn’t exist; why have we failed ?
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Chemoprevention with selenium and vitamin E
 Large randomized placebo-controlled trial of vitamin
E and selenium.
 Show no reduction in PCa period prevalence, but an
increased risk of PCa with vitamin E alone (17%).

6. Paving the future for better prevention strategies
Actions Plan
1. Identify a population any higher risk, then design
prospective trials with new drugs.
2. Enact basic life adjustment at every stage the PCa
care pathway (PRI, SEC, TER prevention)
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7. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
 Gene
 Lifestyle
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SNP Reference
rs4430796
Zheng, N Engl J Med 2008 ; 358 :910-9
Beebe-Dimmer, Int J Cancer 2008 ; 122(12) : 2876-79
Eeles, Nat Genetics 2008 ; 40(3) : 316-21
rs1859962
rs16901979
rs6983267
rs1447295
rs7501939
rs4242382
rs10090154
rs10993994
Eeles, Nat Genetics 2008 ; 40(3) : 316-21
Camp, Canc. Epid. Biomarkers Prev 2009 ; 18(4)
rs266849 Eeles RA et al Nat Genetics 2008 ; 40(3) : 316-21
rs2171492 Ross, BMC Cancer 2009, 9 :69
rs104548 (D302H) Lubahn, The Prostate 2010 ; 70 :646-653
rs9282858 (A49T )
Makridakis NM et al Lancet 1999 ; 354 :975
Li J et al Am J Epidemiol 2010 ; 171 :1-13
rs623419 Lindström S et al Prostate 2006 ; 66 (22) : 11077-83
rs4045402 Lindström S et al Prostate 2006 ; 66 (16) : 1729-43
rs11569681 Thomae BA et al Pharmacogenom J 2002 ; 2 :48
G289S Margiotti K et al The Prostate 2002 ; 53 :65

8. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
 Gene
 Lifestyle
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 There are men at higher risk of PCa because
they carry germline or somatic gene
abnormalities.
 RNASEL, formerly known as HPCI
 BRCA1 and BRCA2, which have also been linked to
breast and ovarian cancer in women
 MSH2, MLH1, and other DNA mismatch repair
genes
 HOXB13
IMPORTANT TO DEFINE A TARGET
POPULATION !

9. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
 Gene
 Lifestyle
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It is urgent to produce, validate, and implement
similar recommendations for Prostate Cancer.

10. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
 Gene
 Lifestyle
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Evidence Decreases Risk. Increases risk
Suggestive BMI (low grade PCa) BMI (advanced, mortality)
Spirits
Dietary Calcium
Weight
Weak Total vegetable
Fish
Coffee
Serum α-tocopherol
Selenim
Dairy food
Milk
Low-fat milk
Dairy and dietary calcium
Supplement calcium
Waist circumference
Height
Adapted from Markozannes et al. Diet, body size, physical activity and risk of prostate
cancer: An umbrella review of the evidence. Eur J Cancer. 2016 Dec;69:61-69.
Daily Diet

11. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
 Gene
 Lifestyle
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Food supplement (FS) blend of pomegranate, green
tea, broccoli and turmeric,
Adapted from : A double-blind, placebo-controlled randomised trial evaluating the effect of
a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer--
the U.K. NCRN Pomi-T study. Thomas R, Prostate Cancer Prostatic Dis. 2014 Jun;17(2):180-6.

12. What causes prostate cancer ?
About Nature, Nurture, and Prostate Cancer Risk
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 2,705 non-metastatic PCa from Health Professionals Follow-Up Study diagnosed observed
from 1990 to 2008; 548 deaths, 20% of which were a result of PCa.
categories of walking duration and pace after prostate cancer diagnosis. An easy pace is less than 2 mile per hour
(MPH), a normal pace is 2 to 2.9 MPH, and a brisk pace is 3 MPH. Adapted from SA. Kenfield et al., J Clin Oncol 29:726-732. 2011
All Cause Mortality PCa Mortality
-54%
It is urgent to produce, validate, and activate
lifestyle recommendation for patients with PCa
and create a support network.

13. Will adherence to diet and physical activity
really impact outcomes ?
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“Adhering to cancer prevention guidelines for diet
and physical activity is consistently associated with
lower risks of overall cancer incidence and mortality,
including for some site-specific cancers.”
Cancer Epidemiol Biomarkers Prev; 25(7); 1018–28.
2016 AACR.

14. Paving the future for better prevention strategies
Conclusions
1. The “Magic” pill, or food supplement doesn’t exist.
2. We must secure that every man concerned about
PCa or treated for it:
1. Receives adequate counselling about genetic and other
risk factors
2. Receives adequate counselling on lifestyle adjustment
(including diet, food supplement and physical activity)
and have adequate access to the infrastructure or
health professional to activate these changes.
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15. 15
3rd EORTC Cancer Survivorship Summit
1-2 March 2018
Brussels, BE