Prostate Cancer for Primary
Care Physicians
NIMIRA ALIMOHAMED MD, FRCPC
MEDICAL ONCOLOGIST, TOM BAKER CANCER
CENTRE
CLINICAL ASSOCIATE PROFESSOR, THE UNIVERSITY
OF CALGARY
Objectives
 Review epidemiology of prostate cancer
 Review management options for early stage disease
 Review recent advancements in the management of
advanced prostate cancer
Epidemiology
Incidence = the number of new cases
per specified time period
Prostate cancer
- Cancer with the highest incidence
in males
- Estimated 24% of all new cancer
cases in men in 2015
Canadian Cancer Statistics 2015
Mortality
Prostate cancer
- accounts for 10% of estimated
cancer deaths in men in 2015
Canadian Cancer Statistics 2015
Canadian Cancer Statistics 2015
Prevalence = proportion of cases in the population at a given time
• Indicates how widespread the disease is (vs. incidence which indicates how
likely it is to develop the disease
• Prostate cancer has a high prevalence AND incidence
Canadian Cancer Statistics 2015
Prognosis of Prostate Cancer
 Early-Stage disease
 Organ confined
 “potentially curable”
5 year survival rate ~100%
 Advanced disease
 Rising PSA (2-10 years)
 Metastatic disease
Castration sensitive state
 Castration resistant state


Death
Survival 2-5 years
Early-Stage Prostate Cancer
“POTENTIALLY CURABLE” DISEASE
Detection of Early-Stage Disease
 80% of men are diagnosed based on abnormal serum
PSA levels

PSA screening
PSA can be falsely elevated – lack of specificity for prostate cancer
 Not all detected cancers require treatment – overtreatment of
many men
 HOWEVER: targeted screening in an optimal population AND a
pre-screening discussion can temper these concerns

Detection of Early-Stage Disease
 Digital rectal examination
 Suggestive of prostate cancer: asymmetry, frank induration,
hard nodules
 Suggestive of BPH: symmetric enlargement and firmness of
the gland
 Can detect tumors in the peripheral (posterior and lateral
aspects) zone
An abnormal DRE should prompt a biopsy
Regardless of PSA level!
Symptoms of Early-Stage disease
 Most men will not have symptoms attributable to the
cancer
 Urinary frequency, urgency, nocturia, hesitancy
 Usually attributable to underlying BPH (benign prostatic
hypertrophy)
 Hematuria, hematospermia
 Uncommon
www.uptodate.com
Diagnosis of Early Stage Disease
 Refer to UROLOGY for PROSTATE BIOPSY if:


Abnormal DRE
Elevated PSA*
 Transrectal prostate biopsy typically performed with
transrectal ultrasound guidance (TRUS)



Areas of concern on TRUS are typically hypoechoic
TRUS is used to guide biopsy
12 cores are typically taken
 MRI guided biopsy currently being evaluated in specific
situations

Example: Previous negative biopsies
Risk Stratification for Localized Prostate Cancer
 PSA
 Stage (T stage)

How big is the tumor?
 Grade (Gleason Scoring System)
 How
aggressive does the cancer look?
Tumor Staging
Clinically inapparent
Organ confined
T1
T2
T3
T4
Extension through prostatic capsule
Fixed or invades adjacent structures
Detailed Tumor Staging
T1
Cancer in prostate only. Cannot be felt and is not visible by imaging.
T1a
Discovered on prostate resection (TURP), less than 5% prostate tissue affected
T1b
Discovered on prostate resection, more than 5% prostate tissue affected
T1c
Cancer detected by elevated PSA only
T2
Cancer in prostate only, though more advanced. Detected during DRE.
T2a
One half or less of one side
T2b
More than half of one side
T2c
Both sides
T3
Cancer spread to nearby areas (blood vessels, nerves, seminal vesicles).
T3a
Has spread outside prostate, but not to seminal vesicles
T3b
Has spread to seminal vesicles
T4
Cancer spread into wall of pelvis.
Prostate Cancer Grading
 Grade indicates cancer’s aggressiveness - how
fast it is likely to grow & spread
 Pathologist looks at the 2 largest sections of
cancer in the tissue specimens and assign each a
Gleason Grade ( 2 to 5 / 5 )
 The two grades are added to give an overall
Gleason Score (e.g. 3 + 4 = 7 /10)
Risk Group Stratification
 Using
the T stage, Gleason score and PSA
result, we can classify men with localized
prostate cancer into risk groups:
Very-Low Risk
Low Risk
Intermediate Risk
High Risk
Very-High Risk
Very Low Risk disease
 VERY LOW RISK
 T1 AND
 Gleason < 6 AND
 Serum PSA < 10 AND
 Limited disease within the gland
< 3 positive biopsy cores
 < 50% involvement of any one core
 PSA density < 0.15


Management options:
Active surveillance reasonable (if life expectancy < 20 years
 Any other option if life expectancy > 20 years

Low Risk Disease
 LOW RISK localized prostate cancer
 T1 – T2a
 Gleason < 6
 PSA < 10

Management options:
Active surveillance
 Radiation therapy
 External beam radiation
 Brachytherapy
 Radical prostatectomy
 (Cryotherapy)

Intermediate Risk Disease
 Intermediate Risk localized prostate cancer

T2b-T2c (extensive disease localized within the gland) OR
Gleason 7 OR
PSA between 10 and 20

Management options:


Radiation therapy
 External beam
 Brachytherapy (Gleason 3+4)
 Radical prostatectomy
 (Active surveillance not indicated unless limited life expectancy)
 (Cryosurgery in some)

High Risk Disease
 High-risk localized prostate cancer
 T3a (extracapsular extension) OR
 Gleason 8-10 OR
 PSA > 20


**Need staging investigations (CT abdo/pelvis, Bone Scan) to
evaluate for metastatic disease
Management options
Radiation therapy
 External beam + Androgen Deprivation Therapy (ADT)
 Radical prostatectomy +/- ADT
 (Cryosurgery)

Very High Risk Disease
 Very high-risk localized prostate cancer


T3b or T4 disease
Gleason 8-10
Primary Gleason grade 5
 4+ cores with Gleason 8-10



**Need staging investigations (CT abdo/pelvis, Bone Scan) to
evaluate for metastatic disease
Management options
Radiation therapy
 External beam + Androgen Deprivation Therapy (ADT)
 Radical prostatectomy +/- ADT
 (Cryosurgery)

“Doc, what should I do?”
 Example: 68 year old man with intermediate risk
(Gleason 3+4=7/10) disease

Options: Prostatectomy, External beam radiation therapy,
brachytherapy, cryosurgery
 No randomized controlled trials comparing these
approaches
 Retrospective data reports similar outcomes

The PREFERE trial will hopefully shed more light on this
Large, phase III trial ongoing
 Comparing radical prostatectomy, EBRT, brachytherapy, active
surveillance in patients with low or intermediate-risk prostate
cancer

“Doc, what should I do?”
 Choice of therapy depends on:
 Risk stratification
 Informed patient choice:
Estimated outcomes with different treatment options
 Potential complications with each treatment approach


Patient’s general medical condition, age, comorbidities

Online risk calculator

Decisionhelp.truenth.ca
Management of Localized
Prostate Cancer
ACTIVE SURVEILLANCE
P R O S TAT E C TO M Y
BRACHYTHERAPY
E X T E R N A L B E A M R A D I AT I O N
C R YO S U R G E R Y
The Prostate Gland
Pubic Bone
 Understanding this
Bladder
Rectum
Prostate
anatomy is important
if one is to
understand the side
effects and risks of
prostate cancer
treatment
Active Surveillance
(No treatment for now)
WHY? & WHO?

A D E S I R E T O A V O I D O R D E L AY D E A L I N G W I T H T H E S I D E E F F E C T S A N D
R I S K S O F T R E AT M E N T

O T H E R H E A LT H P R O B L E M S M AY B E M O R E S I G N I F I C A N T F O R A PAT I E N T
SUCH AS: DIABETES, HEART DISEASE, ALCOHOLISM

I N F O R M E D PAT I E N T C H O I C E

A 2 0 1 2 S T U D Y W I T H 1 2 Y E A R F O L L O W U P S H O W S FA V O R A B L E R E S U LT S
(PIVOT- NEW ENGLAND JOURNAL OF MEDICINE)

T H E R E I S A N A C T I V E S U R V E I L L A N C E P R O G R A M AT T H E P R O S TAT E
C A N C E R C E N T R E F O R M O N I T O R E D F O L L O W U P.
Active Surveillance
(No treatment for now)
H OW ?

C H EC K U P S , & D R E W I T H YO U R D O C TO R

R E P EAT P SA

R E P EAT B I O P S I ES

A C H A N G E M AY L EA D TO I N T E RV E N T I O N
PROSTATECTOMY
(Surgical removal of the prostate)
WHO?
D I S E A S E C O N F I N E D T O T H E P R O S TAT E
F I T F O R S U R G E R Y
P S A L E S S T H A N 2 0
I N F O R M E D PAT I E N T C H O I C E
PROSTATECTOMY
(Surgical removal of the prostate)
WHERE?
ROCKYVIEW HOSPITAL
UNIT 82 (POST OPERATIVELY)
PROSTATECTOMY
(Surgical removal of the prostate)
HOW?
OPEN OR ROBOTIC
UNDER ANESTHESIA
NERVE SPARING SURGERY
PROSTATECTOMY
(Surgical removal of the prostate)
 H O S P I TA L STAY U S UA L LY 2 - 3 DAYS
 M I N I M A L D I S C O M FO RT
 FO L E Y C AT H E T E R I N P L AC E : 1 - 2 W E E KS
 3 - 6 W E E KS O F F WO R K
PROSTATECTOMY
(Surgical removal of the prostate)
A DVA N TAG ES
W E L L T O L E R AT E D
LY M P H N O D E S C A N B E E X A M I N E D
A S S E S S M E N T O F M A R G I N S BY PAT H O L O G I S T
P S YC H O L O G I C A L R E L I E F
E XC E L L E N T L O N G - T E R M R E S U LT S
E R E C T I L E F U N C T I O N M AY R E T U R N O V E R S E V E R A L W E E K S T O
YEARS
PROSTATECTOMY
(Surgical removal of the prostate)
S I D E E F F EC TS A N D R I S KS
 E R E C T I L E D Y S F U N C T I O N : 5 0 - 6 0 / 1 0 0 M E N - T R E ATA B L E
 I N C O N T I N E N C E ( S T R E S S ) : 1 5 / 1 0 0 M E N - T R E ATA B L E
LESS COMMON
 SEVERE INCONTINENCE: <1/100 MEN
 BLADDER NECK CONTRACTURE: 1-7/100 MEN
 R E C TA L I N J U R Y: R A R E
Robotic Prostatectomy
Robotic Prostatectomy
 State-of-the-art
robotic technology
 3-D Visualization
Prostatectomy access
Open Surgical Incision
Robotic Prostatectomy Incision
Brachytherapy
W H AT I S I T ?
P E R M A N E N T I N S E R T I O N O F R A D I O A C T I V E
S E E D S I N T O T H E P R O S TAT E G L A N D
 COMPUTER GUIDED
A WAY O F F O C U S I N G A N D D E L I V E R I N G A
H I G H E R D O S E O F R A D I AT I O N
Brachytherapy
WHO?
L O W R I S K G R O U P
S O M E PAT I E N T S I N T E R M E D I AT E R I S K G R O U P

Gleason 3+4, PSA <10 / Gleason 3+3, PSA<15
P R O S TAT E G L A N D L E S S T H A N 5 0 C C
I N F O R M E D PAT I E N T C H O I C E
Brachytherapy
Brachytherapy
What to expect
 Preoperative consult with anesthesiologist
 Prescriptions for:

Flomax: Started 1 week prior to procedure

Antibiotic: 7 days- Start 1 day prior to procedure
 Diet and bowel cleansing 1 day prior to treatment
Brachytherapy
 Half life of seeds: 2 months
 Precautions:
 Carry
Amount of Radiation Left (%)
a wallet card for security
 Holding
children
 Sleeping
 Voiding
with partner
seeds
Time (months)
Brachytherapy
Advantages
 A day surgery procedure 1.5 - 2 hours
 Bladder catheter removed the following
day
 Quick recovery
Brachytherapy
Side Effects and Risks
 Early (1- 6 months)
 Irritation
of the bladder and urethra
Burning, frequency, urgency
 Late
 Erectile
dysfunction: 20 – 50/100 men
 Urethral stricture: 1/100 men
May require dilatation
External Beam Radiation
( High energy x-rays )
WHO?
Any patient with prostate cancer
Patients ineligible for surgery
Informed patient choice
External Beam Radiation
( High energy x-rays )
WHO NOT?
 Ulcerative colitis, Crohn’s disease, Diverticulitis
 Previous radiation to the pelvis
 Previous extensive pelvic surgery
External Beam Radiation
What to expect
 Image-guided Radiation Therapy
 CT Scan for treatment planning with bowel
and bladder prep
External Beam Radiation
What to expect
 Daily x-rays on treatment machine for targeting
 Daily outpatient treatments
 Monday
– Friday, 5 treatments/ week
 30 minutes at the cancer clinic daily
 12 minutes on treatment machine daily
 37- 40 treatments (8 weeks)
External Beam Radiation
Advantages
 Outpatient treatment
 Treatment times can be flexible
 No anesthetic required
 Patients often continue to work during therapy
 Treatment beamed at the prostate and the immediate
surrounding area
External Beam Radiation
Side Effects and Risks
Early
 Fatigue
 Irritation
of the bowel and bladder
(frequency of urination, burning, diarrhea)
Easily
managed
Recovery within
4-6 weeks of finishing
External Beam Radiation
Side Effects and Risks
Late
 Erectile
Dysfunction 40-60 / 100 men
 Bladder
complications (frequency, urgency)
 Rectal
or bladder bleeding (15-20/ 100 men)
 Bleed
requiring treatment 1/100
Cryosurgery
What is it?
 Insertion of hollow needles into the
prostate used to freeze the prostate
 Prostate gland is frozen, allowed to thaw,
and frozen again
Cryosurgery
WHO?
 U S U A L LY O L D E R M E N
 ALL GRADES OF CANCER, PSA < 20
 P R O S TAT E G L A N D V O L U M E < 6 0 C C
 S A F E O P T I O N F O R M E N W I T H O T H E R H E A LT H C O N C E R N S
 I N F O R M E D PAT I E N T C H O I C E
Cryosurgery
W H AT TO E X P EC T





1.5 – 2 HOURS
SPINAL ANESTHETIC
M I N I M A L PA I N
O N E N I G H T I N T H E H O S P I TA L
QUICK RECOVERY 2-3 WEEKS
Cryosurgery
What to Expect After
 Suprapubic catheter for 2-3 weeks
 Must lie flat for 2 hrs each afternoon
 Anti-inflammatory and antibiotic used for
7-10 days
Cryosurgery
Side Effects and Risks
Early
 Swelling of scrotum and penis
 Discomfort with sitting (less than 2 wks)
 Erectile dysfunction-potential for recovery 30% over
time
Cryosurgery
Side Effects and Risks
Late
 Stress incontinence: 5 /100 men
 TURP needed: 2-3 /100 men
Management of Localized Prostate
Cancer
Side effects/risks of treatment
 The side effects and risks of treatment relate to the fact that
the prostate gland sits very close to bowel, bladder and nerves
 All treatments result in infertility
 Treatment of Prostate cancer does not mean the end of a
healthy sex life
 An erection , orgasm and climax are still possible although
dry.
Risk Groups
LOW
INTERMEDIATE
PSA
Gleason
score
<10
T- Stage
T1-T2b
Treatment
Options
- Prostatectomy
- Surveillance
- EBRT (External Beam
- Prostatectomy Radiation Therapy)
- Brachytherapy - Cryotherapy
- EBRT
- Brachytherapy(a
subset of pts.)
- Cryotherapy
- Surveillance
and
<=6
10 - 20
or
7
HIGH
> 20
8-10
or
or
and
or
T2c
T3,T4
- EBRT & ADT
- Prostatectomy
- Cryotherapy
How Do We Assess Whether Treatment is
Working?
•
•
E X A M I N AT I O N ( D R E )
P SA
Expect undetectable levels at 3 months for
surgical treatments
(prostatectomy and cryotherapy)
 Falls over months to 3 years for radiation
treatment ( EBRT and Brachytherapy)

Surveillance post-treatment
 Recommend PSA testing q6months x 5 years * then
annually
 DRE annually (if radiation therapy received)

DRE required if PSA detectable in patients after surgery
 Active surveillance patients should have a repeat
prostate biopsy

Usually 1 year after initial diagnosis then at selected intervals
Disease Recurrence
 All initial treatments have a backup treatment plan if
necessary for local recurrence

Open/Robotic: EBRT

Brachy: Cryo

EBRT: Cryo

Cryo: Cryo again, EBRT
Advanced Prostate Cancer
Evolution of Prostate Cancer
 Localized disease



Typically cured with above approaches
Many men will die of other causes
~15% will go on to develop advanced disease
 PSA recurrence



Rising PSA level can indicate local recurrence or distant metastatic
disease
“Rising PSA” state may start years after initial diagnosis and persist
for years without evidence of metastatic disease
Androgen Deprivation Therapy may be initiated at this time
 Metastatic/Advanced disease


~10% of all cases of prostate cancer will present with metastatic
disease
Bone and lymph node metastases are most common
Medscape Education - Oncology
PSA recurrence
 Investigations required:
 Repeat PSA test (doubling time is important)
 May need prostate bed biopsy
 Bone Scan
 CT scan
Androgen Deprivation Therapy
 Testosterone is the primary driver of prostate cancer
growth
 Androgen deprivation therapy (ADT) is the mainstay
of medical treatment for patients with prostate
cancer

High-risk localized prostate cancer


Rising PSA state


Combined with RT (total of 2 years)
Intermittent or continuous therapy
Metastatic prostate cancer *
Goals of therapy in advanced prostate cancer
 Quantity of life
 Quality of life
 Improvement in pain, obstructive symptoms, time to skeletalrelated events
Androgen Deprivation Therapy
 Can be achieved by:
 Surgical orchiectomy
 Medical ADT

Typically consists of continuous GnRH agonist therapy
 Example: Leuprolide (lupron), Guserelin (Zoladex)
 Delivered by subcuteneous injections q3-6months
 Combined initially with an antiandrogen to prevent testosterone flare
• Example: bicalutamide (Casodex) x 1 month

Mechanism:
 Bind to GnRH receptors, cause initial LH/FSH release and testosterone
flare, the downregulation of GnRH receptors, then a decrease in production
of LH/FSH and testosterone.

GnRH antagonists
 Example: Degarelix (Firmagon)
 Delivered by MONTHLY sc injections
 New, efficacious, prevent need to block the testosterone flare
 GnRH agonists remain preferred agents due to funding issues, frequency of
injections
ADT – side effects
 Sexual dysfunction



Loss of libido
Erectile dysfunction
Management:

Couples counselling prior to ADT initiation, therapy, pharmacologic
strategies
 Osteoporosis


Osteoporotic fractures can be detected in 20% of men on ADT at 5
years
Management:
Lifestyle interventions
 Calcium and Vitamin D supplementation
 Bone Mineral Density testing at initiation of ADT
 Consider osteoclast inhibition with bisphosphonates or denosumab

ADT – side effects
 Vasomotor symptoms
 Hot flashes, nausea, sweating, sleep disturbances
 Management:
Medroxyprogesterone, cyproterone acetate, venlafaxine and
gabapentin have all been evaluated with varying degrees of success
and side effects
 Gabapentin:
 Phase III trial evaluated 223 men with hot flashes
 900mg gabapentin vs placebo reduced frequency and intensity
of hot flashes and was well tolerated
 Acupuncture

Loprinzi CL et al Ann Oncol 2009)
ADT- side effects
 Body composition
 Loss of lean body mass, increased body fat, decreased muscle strength, decreased
insulin sensitivity
 Management:


Moderate exercise regimen
Increased screening for diabetes and elevated cholesterol
 Cardiovascular effects
 Conflicting studies regarding the impact on ADT on cardiovascular health
 Those with a previous history of CVD are at increased risk
 Management:





Counseling and risk reduction
Fatigue
Anemia
Gynecomastia
Emotional and cognitive changes
Chemotherapy in prostate cancer
 Administered in the castration-sensitive and castration-
resistant states
 Examples:


Docetaxel IV q3weekly with daily prednisone
Cabazitaxel IV q3weekly with daily prednisone
 Given for up to 10 cycles
 Side effects:






Fatigue
Cytopenias (anemia, febrile neutropenia)
Infections
Neuropathy
Alopecia
Fluid retention, edema
Novel hormonal strategies
 Castration-resistant prostate cancer
 When the PSA rises despite ADT
 Due to resistance mechanisms

Intratumoral testosterone production
 Abiraterone Acetate
 CYP17 inhibitor, decreases testosterone production
 Oral administration, along with prednisone 5mg BID
 Side effects: fluid retention, HTN, hypokalemia, LFT
abnormalities
Novel hormonal strategies
 Enzalutamide



Novel, potent androgen-receptor blocker
Oral administration
Side effects: fatigue, gynecomastia, hot flashes
 Many other agents currently in development:



Oral hormonal agents
Immunotherapy
Radiopharmaceuticals
 Each therapy is used in sequence, survival gains can be
significant.
 Many questions remain:

Optimal sequence of therapy, selection of patients, biomarkers
Bone-Targeted Therapy
 Bisphosphonates and Denosumab have been found
to improve outcomes in patients with metastatic
prostate cancer

Decreases time to skeletal-related events



Hypercalcemia, spinal cord compression, fractures, pain requiring
palliative RT
Often prescribed in conjunction with other treatments and
continued indefinitely
Monitor for impaired renal function, hypocalcemia and
osteonecrosis of the jaw
KEY POINTS
Summary
 Prognosis for most men with prostate cancer is excellent.

Prostate cancer survivors have a higher chance of death from other
causes
 90% of patients will present with localized disease


Due to widespread PSA screening
However, concerning symptoms should prompt a work-up (bone
pain, urinary tract obstruction, hematuria)
 There are a few reasonable treatment options for early-
stage disease. Decision making depends on risk
stratification, age, comorbidities, and patient’s informed
choice.
Summary
 Each treatment modality may result in late side-effects .
 Sexual dysfunction is common after treatment for
prostate cancer.
 Patients treated with ADT should have careful
assessment and monitoring of cardiovascular health.
Other complications include impaired glucose
metabolism and osteoporosis.
 Psychosocial resources should be offered to patients, and
their partners.
 A rising PSA post-treatment warrants a prompt
discussion with the oncology team.
Summary
 Patients with advanced prostate cancer are living
longer with more treatment options.
 The quality of life of these patients is often improved
with treatment, despite the side effects of treatment.
 Pain is often a major component of morbidity due to
advanced prostate cancer.
 Communication between the oncology team and
primary care physicians is paramount to ensure
quality care (oncology, supportive, palliative).
QUESTIONS?