PROSTATE CANCER: THE BASICS IN 2015

Neil Fleshner MD MPH FRCSCMartin Barkin Professor & Chairman of Urology

(Surgery)University of Toronto

Head, Division of UrologyUniversity Health Network (Princess Margaret

Hospital)John & Nancy Love Chair in Prostate Cancer

Prevention

BASIC ANATOMY

PROSTATE CANCER 2015

•Most common malignancy in man (17.7% lifetime risk)

•2ndmost common cause of cancer deaths in men (3-4%)

•Potential for overdetection/overtreatment•Treatments for early disease has associated

morbidity

RISK FACTORS

•Family History•Age•Race

–African Canadians•Diet & Lifestyle

Copyright ©2005 American Cancer SocietyFrom Parkin, D. M. et al. CA Cancer J Clin 2005;55:74-108.

Age-standardized Incidence and Mortality Rates for Prostate Cancer

PROSTATE CANCER:EARLY ONSET (Sakr et al)

DECADEISOLATED PINCANCER

20-29

30-39

40-49

9%

16%

26%

---

31%

34%

HGPIN

BIRTH

MICROSCOPIC

STAGE T1/2

METASTASES

DEATH

TIME

Unfavorable Environment (USA/Canada)

? Modified Environment (Complementary)

Favorable Environment (China/Japan)

TOPICS

•How to prevent prostate cancer?•How to find it early?•What’s new in treatment?

HAZARD CURVE

(Lippman SM, et al. JAMA, 2009)

RANDOMIZED TRIAL OF COMBINATION VITAMIN E,

SELENIUM AND SOY PROTEIN AMONG MEN WITH HIGH GRADE PROSTATIC INTRAEPITHELIAL

NEOPLASIA (HGPIN)

Fleshner N, Kapusta L, Hersey K, Farley A, Lawrentschuk N, Donnelly B, Chin J, Gleave M , Klotz L, Trypkov C, Tu D, Parulekar W, for the

National Cancer Institute of Canada Clinical Trials Group

CANCERS

•26.4% developed invasive PC•HR for nutritional supplement

–1.03 (95% CI 0.67-1.60)•Gleason score distribution same among 2

groups•Baseline age, weight, PSA and T not predictive

of PC development•Supplement well tolerated with only flatulence

more prevalent in the soy/E/selenium arm (27 vs 17%)

SWOG PIN STUDYMarshall et al

Cancer Prev Res 2011:11:1761

•428 patients @ 3 year follow up biopsy•No benefit in HGPIN

–Cancer rates•Placebo 36.6%•Selenium35.6%

Volume 349:215-224July 17, 2003Number 3

The Influence of Finasteride on the Development of Prostate Cancer

Ian M. Thompson, M.D., Phyllis J. Goodman, M.S., Catherine M. Tangen, Dr.P.H., M. Scott Lucia, M.D., Gary J. Miller, M.D., Ph.D., Leslie G. Ford,

M.D., Michael M. Lieber, M.D., R. Duane Cespedes, M.D., James N. Atkins, M.D., Scott M. Lippman, M.D., Susie M. Carlin, B.A., Anne Ryan, R.N.,

Connie M. Szczepanek, R.N., B.S.N., John J. Crowley, Ph.D., and Charles A. Coltman, Jr., M.D.

Gleason Score Total Number of Cancers

Gleason Score Total Number of Cancers

Not graded: Finasteride n=46, Placebo n=79

N = 4368N = 4692

REDUCE: Study Design

Matching placebo

2-year 10-core biopsy

4-year 10-core biopsy Randomization

-7 02448

Entrybiopsy

Studymonth:

Dutasteride 0.5 mg daily

-1

Study entry

Protocol-independent biopsies could occur as indicated

Andrioleet al. J Urol 2004; 172: 1314–7

NCIC –PRP1

•RCT of Soy, Vitamin E, Selenium among Pts with HGPIN (2 biopsies)

•Endpoint: Invasive cancer @ 3 years•40gm Soy Protein•Vitamin E 800 IU•Selenium 200 micrograms

REDUCE: Primary endpoint

Dutasteride reduced the risk of prostate

cancer over 4 years by 23%

p<0.0001

REANALYSISUSING

MODIFIEDSYSTEM NOW

STATISTICALLYSIGNIFICANT

p=0.03

DRILLING DOWN THE NUMBERS FROM PCPT AND REDUCE

•NNT’s to prevent 1 cancer–PCPT /REDUCE16.6-19.2

•NNT’s to “cause” 1 high grade cancer–PCPT/REDUCE150-200

•Therefore if you treat 200 men–Prevent: 10-12 cancers and diagnose 1 high

grade tumor–Benefit/harm Ratio : 10-12 to 1

HOW TO DETECT PROSTATE CANCER:

Mandatory: PSA/Physical Exam

Where do we stand withProstate Cancer screening in 2015?

Neil Fleshner MD MPH FRCSC

Prostate Cancer Incidence and Mortality

National Cancer Institute 2011

PSA screening: PLCO

•13 yr follow up•Prostate Cancer Mortality RR 1.09 (95% CI = 0.87 to 1.36)

•1993-2001, 76,693 men randomized

–Screening vs usual care

–52% contamination

Andriole et al., NEJM 2009Andriole et al., JNCI 2012

PSA screening: ERSPC162,000 men randomized, 7 countries-contamination 23-40%

•13 year follow up•Prostate Cancer Mortality: RR 0.79 (0.69-0.91),

p=0.0007•NNS = 781, NND = 27

Schroder et al., NEJM 2009Schroder et al., Lancet 2014

PSA screening: Goteborg Screening Trial

•20,000 men, aged 50-64•14 years median follow up•Prostate Cancer Mortality RR: 0·56 (95% CI 0·39–0·82;

p=0·002)•NNS = 293 NND = 12

Hugosson et al., Lancet Oncol 2010

USPSTF: Updated Recommendation

www.canadiantaskforce.ca

•6 Task Force members and Public Health Agency of Canada, national and international external reviewers

•Endorsed CFPC•For men with LUTS (nocturia, urgency, frequency

and poor stream) or BPH•Irrespective of DRE results (DRE not

recommended)•No distinction for race (african-canadians) or family

historyCTFPHC, CMAJ 2014www.canadiantaskforce.ca

Conclusions

•Despite 6 screening trials (2 of high quality),controversystill exists over PSA screening

•Most specialty groups recommend adaptedscreening for prostate cancer andshared-decision making

•The Canadian and US Task Forces recommend against PSA screening

TREATMENT OF PROSTATE CANCER IN 2015

•Active Surveillance•Surgery

–Open–Robotic

•Radiation Therapy–External Beam–Brachytherapy

•HIFU•Hormone Therapy/ Chemotherapy•Watchful waiting

ACTIVE SURVEILLANCE

•Different concept to watchful waiting–Men fit for radical therapy–Low risk (?low-intermediate risk)–Serial observation including PSA and repeat

biopsy–Intervene if necessary

•PSA kinetics•Biopsy change

–Goal–cure if necessary

OPEN RADICAL

ROBOTIC

RADICAL PROSTATECTOMY

•Common operation•Side Effects

–Blood Loss–Incontinence 8%–Erectile Dysfunction50%–Scar Tissue2%

RADIATION THERAPY

•External•Brachytherapy

–Low dose–High Dose

•Adverse Effects–Incontinence 2-5%–Erectile Dysfunction50%–Rectal toxicity5%

WHAT IS HIFU?

•Simply put: HIFU is an external high energy ultrasound beam precisely focused on a tumor target

1W/cm2

2000 W/cm2

TransducerFocal Point

SONABLATE®500SYSTEM3MM X 3MM X 12MM LESION

SYSTEMIC THERAPIES

•Castration Sensitive–ADT

•Castration Resistant–Chemotherapy–Radium 223–Enzalutamide/Abiraterone–Denosumab/Zolendronic Acid

CONCLUSION

•Common disease and a major killer•Research dollars are the key•Advances are being made+++++•Please get your (or your loved one)PSA

checked

MORBIDITY OF PROSTATE CANCER TREATMENT

•SURGERY–Urinary incontinence–Erectile dysfunction

•RADIATION THERAPY–Urinary incontinence–Erectile dysfunction –Bowel Dysfunction

•HORMONE THERAPY–Psychological change–Muscle weakness–Bone loss–Accelerated cardiovascular effects