Queen’s UniversityQueen’s University

QQueen’s University

Prostate

D. Robert Siemens, M.D.

GU OncologyGU Oncology

● Prostate CancerProstate Cancer– 20,700 cases, 4200 deaths (2006, CCS)20,700 cases, 4200 deaths (2006, CCS)

● Bladder CancerBladder Cancer– 6400 cases, 1700 deaths6400 cases, 1700 deaths

● Kidney CancerKidney Cancer– 4600 cases, 1550 deaths4600 cases, 1550 deaths

● TestesTestes– 840 cases, 30 deaths840 cases, 30 deaths

Web ResourcesWeb Resources

● http://cancernet.nci.nih.gov/cancertypehttp://cancernet.nci.nih.gov/cancertypes.htmls.html

● www.cancer.cawww.cancer.ca● www.cua.orgwww.cua.org● www.cancercare.on.cawww.cancercare.on.ca

ObjectivesObjectives

● To be able to state the two components that To be able to state the two components that can cause bladder obstruction in benign can cause bladder obstruction in benign prostatic hyperplasiaprostatic hyperplasia

● To be able to state 3 management options To be able to state 3 management options for early prostate cancerfor early prostate cancer

● To understand the importance of the To understand the importance of the grading of prostate cancergrading of prostate cancer

Prostate DiseasesProstate Diseases

● Benign Prostatic Hyperplasia (BPH)Benign Prostatic Hyperplasia (BPH)

● Prostate CancerProstate Cancer

● ProstatitisProstatitis

BPHBPH

● Prostate size increases with ageProstate size increases with age

● Total prostate volume increases from Total prostate volume increases from approximately 25 mL for a man in his 30s to 35–approximately 25 mL for a man in his 30s to 35–45 mL for a man in his 70s45 mL for a man in his 70s

● Increased cell numbersIncreased cell numbers– Balance between cell proliferation and impaired Balance between cell proliferation and impaired

apoptosisapoptosis

BPHBPH

● Hyperplasia of epithelial (glandular) or Hyperplasia of epithelial (glandular) or stromal (smooth muscle) componentsstromal (smooth muscle) components

● Commonly cause lower urinary tract Commonly cause lower urinary tract symptoms in men (over 50)symptoms in men (over 50)– Relative obstruction of bladderRelative obstruction of bladder

BPH Risk FactorsBPH Risk Factors● MaleMale● AgingAging● Androgens (testosterone, DHT)Androgens (testosterone, DHT)● Androgen receptorAndrogen receptor● Intraprostatic 5 alpha reductaseIntraprostatic 5 alpha reductase● EstrogensEstrogens● Apoptosis regulationApoptosis regulation● Stromal-epithelial interactionsStromal-epithelial interactions● Growth FactorsGrowth Factors

– bFGF, KGF, EGF, TGF-beta, IGFbFGF, KGF, EGF, TGF-beta, IGF

Static Dynamic

Increased muscle tone

BPH ComponentsBPH Components

Lower Urinary Tract Symptoms Lower Urinary Tract Symptoms (LUTS)(LUTS)

Obstructive (voiding)

Irritative(filling)

• Weak stream

• Hesitancy

• Sensation of incomplete emptying

• Intermittent stream

• Prolonged urination

• Frequency

• Nocturia

• Urgency

• Urge incontinence

Differential DiagnosisDifferential Diagnosis

Phimosis

Vesicosphincter dyssynergia

Bladder cancer

Stenosis of urinary meatus

Urethritis

Urethral carcinoma

Hypertrophy or stenosis of bladder neck

Cystolithiasis

Neurogenic

MyogenicCystitis

Bladder dysfunction (diabetes)

Polyuria

Extrinsic pelvic mass

BPH

Prostate Cancer

Urethral stricture

(Ouslander JG. Am J Med Sci 1997;314(4):214-8; Kasraeian A. www.dcmsonline.org; other references upon request)

αα-Blockers: Mode of Action-Blockers: Mode of Action

● Relaxes prostate and bladder neck Relaxes prostate and bladder neck smooth-muscle tonesmooth-muscle tone

55αα-Reductase Inhibitors-Reductase Inhibitors

Block conversion of testosterone to dihydrotestosterone (DHT) within

the prostate

Transurethral Resection of Transurethral Resection of Prostate (Prostate (TURP)TURP)

Resectoscope Resectoscope

Bladder Bladder

Prostate Prostate

Removal of Removal of Hypertrophied Hypertrophied

TissueTissue

Prostate Cancer is Common!Prostate Cancer is Common!

● 13% lifetime risk of prostate cancer13% lifetime risk of prostate cancer

● 3% lifetime risk of dying of prostate cancer3% lifetime risk of dying of prostate cancer

Prostate Cancer is Common!Prostate Cancer is Common!

● Most common cancer in men (27%)Most common cancer in men (27%)

● 18,200 new cases in 200218,200 new cases in 2002

● 4316 deaths in 20024316 deaths in 2002

● 1 death every 13 minutes1 death every 13 minutes

Roberts ‘99

Prostate Cancer IncidenceProstate Cancer Incidence

Risk factors?Risk factors?

● MaleMale● TestosteroneTestosterone● AgeAge● Others…..Others…..

– family history, race, diet etcfamily history, race, diet etc

Family History in Prostate Family History in Prostate CancerCancer

● First degree relative affected ?First degree relative affected ?– NoNo RR= 1 xRR= 1 x– YesYes RR= 2-3 xRR= 2-3 x– Diagnosed <65Diagnosed <65 RR= 6 xRR= 6 x�≥≥ 3 relatives3 relatives RR= 11 xRR= 11 x

GENETICSGENETICS

● HPC1HPC1

● CAG repeatsCAG repeats

● SDR5A2SDR5A2

VITAMIN EVITAMIN E● AntioxidantAntioxidant

● Plant derived oilsPlant derived oils

● Induces cell cycle arrest in PC-3 , LNCaPInduces cell cycle arrest in PC-3 , LNCaP

● ATBC trialATBC trial

– 1/31/3rdrd reduced incidence @ 4 yrs reduced incidence @ 4 yrs– 41% reduced mortality @ 6 years41% reduced mortality @ 6 years

SELENIUMSELENIUM

● Inconsistent dietary intakeInconsistent dietary intake

● AntioxidantAntioxidant

● Induces cell cycle arrest in LNCaPInduces cell cycle arrest in LNCaP

● Clarke 1312 men with NMSCClarke 1312 men with NMSC

– 200 micrograms selenium as Brewer’s yeast200 micrograms selenium as Brewer’s yeast– 69 % reduced incidence of CaP69 % reduced incidence of CaP

SOYSOY

● Japanese paradoxJapanese paradox

● Isoflavones : Genistein / DaidzeinIsoflavones : Genistein / Daidzein– PhytoestrogensPhytoestrogens– Tyrosine kinase inhibitionTyrosine kinase inhibition– Induce apoptosis in PC-3Induce apoptosis in PC-3 // LNCaPLNCaP

DiagnosisDiagnosis

● Digital rectal examinationDigital rectal examination● PSAPSA

– Serine protease secreted into lumen of prostate glandsSerine protease secreted into lumen of prostate glands– Liquefies semenLiquefies semen– Elevated in BPH, prostate cancer, prostatitisElevated in BPH, prostate cancer, prostatitis

● PSA test characteristicsPSA test characteristics– PSA 4-10 … cancer risk ~25%PSA 4-10 … cancer risk ~25%– PSA >10 … cancer risk ~50-60%PSA >10 … cancer risk ~50-60%

Prostate Cancer Stage Prostate Cancer Stage

T1

incidental

T1a, T1b, T1c

T2

confined

T2a, T2b, T2c

T3

locally invasive

T3a, T3b, T3c

T4

fixation

T4a, T4b

Organ Confined Disease Treatment Organ Confined Disease Treatment OptionsOptions

● Radical Surgery Radical Surgery

● Radiation (ext beam and brachytherapy) Radiation (ext beam and brachytherapy)

● Watchful Waiting Watchful Waiting

Advanced Prostate CancerAdvanced Prostate Cancer

Management of Advanced Prostate Management of Advanced Prostate CancerCancer

● Use hormonal therapy to control Use hormonal therapy to control progressive or metastatic diseaseprogressive or metastatic disease

Charles HugginsCharles Huggins1901-19981901-1998

● Awarded Nobel Prize in 1966Awarded Nobel Prize in 1966

● Only Canadian-born doctor to win the Only Canadian-born doctor to win the Nobel Prize in Physiology or MedicineNobel Prize in Physiology or Medicine

CastrationCastration

● Decrease prostate volumeDecrease prostate volume

● Primary tumor shrinks (30-40%)Primary tumor shrinks (30-40%)

● Metastatic deposits decrease (40-80%) and Metastatic deposits decrease (40-80%) and disappear (5-10%)disappear (5-10%)

Surgical CastrationSurgical Castration

● Immediate and complete castrate levels Immediate and complete castrate levels (0.2 ng/ml) (0.2 ng/ml)

● Adrenal androgens (5-10%)Adrenal androgens (5-10%) 1940$1940$

Medical CastrationMedical Castration

● LH-RH agonistsLH-RH agonists– suppression after initial flare of LH and Tsuppression after initial flare of LH and T

– castrate levels of T (0.2-0.5 ng/ml) in 9 days to castrate levels of T (0.2-0.5 ng/ml) in 9 days to 4 weeks4 weeks

– need to treat “flare” with antiandrogenneed to treat “flare” with antiandrogen

Medical CastrationMedical Castration

● LH-RH agonistsLH-RH agonists– goserelin (Zoladexgoserelin (Zoladex®®), leuprolide (Lupron), leuprolide (Lupron®®), ),

buserelin (Suprefactbuserelin (Suprefact®®))

– depot injections 1 to 3-4 monthsdepot injections 1 to 3-4 months

4500-8000/$ year4500-8000/$ year

Adverse EffectsAdverse Effects

● CastrationCastration– loss of libido and potency (>75%)loss of libido and potency (>75%)– hot flashes (50-60%)hot flashes (50-60%)– sweating (10%)sweating (10%)– painful gynecomastia (~1-2%)painful gynecomastia (~1-2%)– osteoporosis (5% fracture)osteoporosis (5% fracture)– cardiovascular effectscardiovascular effects– weight gain, loss of muscle massweight gain, loss of muscle mass