New advancements in the treatment of prostate cancer

New Advancements in the Treatment of Prostate Cancer

Simon Treissman MD FRCSCRoyal Inland Hospital

Department of Surgery

Kamloops RotaryHilton Doubletree Kamloops

November 27, 2013

New Advancements in the Treatment of prostate Cancer

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Discussion:– Structure and Function of the normal prostate gland– What can go wrong with the prostate?– The problem of prostate cancer– Historical Perspectives– Traditional therapies– New advancements– The future

What is the prostate gland?

• What does a normal prostate gland look like?

Bladder

Prostate

Urethra

The prostate is located at the base of the bladder. Urine must pass through it on its way to the toilet.

Schematic


• Where in the body is the prostate gland located?

Anatomical image


• What does the normal prostate gland do?– Largest, most active male sex gland– Located at the base of the male pelvis– Lies “astride” the male urethra– Produces most of the ejaculate by volume– Ranges in size from 10 – 25 grams– Healthy function is necessary for successful fertilization.

The Abnormal Prostate Gland (pathology)

• What can go wrong with the prostate gland?– Postatitis– Benign Prostate Hyperplasia (BPH)– Prostate Cancer (ACP)

Anatomical Schematic

The Abnormal Prostate Gland: Prostate Cancer

• What can go wrong with the prostate gland?– Age dependant– Immortal “Clone” of malignant cells– Originates within the “peripheral zone”– Can “invade” and “metastasize”

Prostate cancer

Schematic


• What can go wrong with the prostate gland?– ACP anatomical images


• Local “invasion”• Prostatism (LUTS)• Bladder outlet obstruction• Hydronephrosis• Renal Insufficiency• Obstructive Renal Failure


• Metastatic Disease• Lymph nodes• Skeletal “mets”

– Skull– Spine– Ribs


• What can go wrong with the prostate?– ACP metastatic disease

The abnormal Prostate Gland: Prostate Cancer

• Incidence of prostate cancer by age:

0102030405060708090

10 20 30 40 50 60 70 80 90

Averagenumber ofcases per year(100's)

Average Number of new cases per yr UK – 2008 – 20102.

ACP is age dependent

Consider the Human Male: Historical PerspectiveEvolutionary considerations

• Primitive / Modern

Survive

Procreate

Evade predators / seat beltHunt wooly mammoth / jobFind suitable shelter / mortgage

Harem / Marriage

Consider the primitive Human Male:

• Primitive Man (3 million years)

– Life is tough• No running water / sanitation, unsatisfactory housing, inadequate

food, no textiles• Predators, microbial illnesses, viral illnesses, no vaccination

– Life is short• Life Expectancy at Birth (LEB) = early forties

Consider the modern Human Male:

• Modern Man ( 200,000 - 50,000 years)

– Life is good!• Lots of carbohydrates, protein, foods out of season• Better living conditions• Relative freedom from predators / pathogens

This happy Canadian fellow can expect to live to 80!


• “Rectangularization” of the survival curve

Survivors out of 100,000 born alive by age, Canada1

100

50

25

10 20 30 40 50 60 70 80 90

1981 -

1951 -

1921 -


• Primitive man VS Modern man

LEB = 40 years LEB = 80 years

Life has changed but procreation hasn’t


• Combination of age related incidence and growing life expectancy -


• “Traditional” Treatments for prostate cancer– Surgery– Irradiation (XRT / EBRT)– Hormonal manipulation (ADT)

New Advancements in the Treatment of prostate CancerTraditional Therapy

• Surgery– Radical Retropubic Prostatectomy (RRP)

Terence Millin (1940’s)– “Anatomical” RRP Patrick Walsh (1980’s)

“Bzzzzzzzz zzzzzzzz”


Irradiation (XRT)

Radium (1920’s)X-ray therapy (1930’s)Cobalt 60 (1940’s - p)Linear accelerator (1950’s – p)“Brachy” therapy (1960’s - p)


• Hormonal manipulation– Charles Huggins– Born Halifax, Nova Scotia, 1901– BA Acadia 1920– MD Harvard 1924– Surgery (Urology) Chicago 1930 – University of Chicago 1930 – 1969– Nobel prize medicine– Chancellor Acadia 1972 - 1979



• Advanced prostate cancer– “Huggins operation” Bilateral orchiectomy (castration)– Delivers remission of 18 months – 5 yrs!– Estrogens (stilbestrol)– Progestins (AndrocurR)– LHRH agonist antagonists– “non” steroidal androgen antagonists


• Surgery– Suitable for younger healthier ACP patient– Minimally invasive (laparoscopic) procedures– Robotic Surgery ( da Vinici surgical robot)


• Irradiation– Brachytherapy

• 1960’s Au 98 (98Au)• 1990’s Iridium 192 (192Ir)• 2000’s Iodine 125 (125I)• High Intensity Focused Ultrasound (HIFU)

– Proton Therapy• Particle accelerator• Increased Dose intensity• Improved precision


• Hormonal Manipulation – Huggins operation– Estrogens– Progestins– LHrH’s– Non-steroidal agents

– Intracellular ADT therapy• Abiraterone (ZytingaR)• Enzalutamide (XtandiR)

abiraterone

“Abiraterone targets testosterone receptor inside the cell”


• Intra-cellular anti-androgens– Enzalutamide

• Reduces PSA by on average 89%• Extended survival by on average 5 months• Relatively non-toxic• FDA stopped trials in November 2011 – rushed to market


• RIH department of surgery– Established 1905– All major specialties represented– Major cases undertaken everyday – 24 / 7 / 365 coverage– Current OR completed 1962

Health & Medicine

New advancements in the treatment of prostate cancer