Prostate cancer

Jay Nayak, MD FRCSC

Assistant Professor of Surgery
Section of Urology
jnayak@sbgh.mb.ca
Good resources:
• Canadian Urologic Association: cua.org

• Prostate Cancer Canada: prostatecancer.ca

Outline
• Epidemiology
• Diagnosis
• Staging
• Natural history
• Management
• Localized disease
• Hormone naïve metastatic prostate cancer
• Castrate resistant prostate cancer (CRPR)
EPIDEMIOLOGY
 Approximately 1 in 7 Canadian men are expected
to be diagnosed with prostate cancer in their lifetime

Canadian Cancer Statistics 2018

Canadian Cancer Statistics 2017
Canadian Cancer Statistics 2017
In 2017: 21,300 Canadian men new men will be diagnosed with prostate
cancer

In 2017: 4,100 Canadian men men will die from prostate cancer

Canadian Cancer Statistics 2018

American Cancer Society 2018
Risk factors
• Age
• Age (over 50) is the strongest risk factor for prostate cancer

• Family history of prostate cancer

• First-degree relative (father/brother)

• Race
• More common among African men
• Asian males have lower risk
DIAGNOSIS
How do we detect prostate cancer?

PSA Screening
Digital Rectal Examination (DRE)
PSA Screening
• PSA is imperfect
PSA Screening
PSA screening for prostate cancer may reduce risk of
prostate cancer mortality but is associated with harms
including false-positive results, biopsy complications,
and overdiagnosis in 20 percent to 50 percent of screen-
detected prostate cancers…

…For men aged 55 to 69 years, the decision to undergo

periodic PSA-based screening for prostate cancer should
be an individual one and should include discussion of the
potential benefits and harms of screening with their
clinician….
- USPTF 2018
 PSA Screening and shared-decision making
Pros Cons
PSA screening may help you detect prostate cancer early. Some prostate cancers are slow growing and never spread

Cancer is easier to treat and be cured if it's diagnosed in the early stages of Not all prostate cancers need treatment. Treatment for prostate cancer may
the disease. have risks and side effects.

PSA testing can be done with a simple, widely available blood test. PSA tests aren't foolproof. It's possible for your PSA levels to be elevated
when cancer isn't present, and to not be elevated when cancer is present.

For some men, knowing is better than not knowing. Having the test can A diagnosis of prostate cancer can provoke anxiety and confusion. Concern
provide you with a certain amount of reassurance — either that you that the cancer may not be life-threatening can make decision-making
probably don't have prostate cancer or that you do have it and can now complicated.
have it treated.
How do we diagnosis prostate cancer?
• Prostate biopsy
• Ultrasound guided
• Standard template: (10-12 cores recommended)
• Too little: Not enough sampling
• Too much: Increased morbidity (infections, etc)

• MR fusion
• Lesion only vs lesion plus standard template
STAGING
Clinical stage
PSA
Gleason score
Clinical
staging is Tumor not palpable

based on - Incidentally detected on TURP

- Elevated PSA → biopsy

DRE
Palpable tumor
- Any PSA (even low) → biopsy

Palpable tumor that feels like it extends

beyond prostate
- Any PSA (even low) → biopsy
Clinical vs. Pathological staging
• Clinical staging is based on the DRE/PSA +/- imaging

• Pathologic staging is based on radical prostatectomy specimen (and

lymph node) analysis
Gleason grade
Histological
appearance of
prostate cancer cells:
extent of glandular
differentiation and
the pattern of
growth in the stroma

Low High
grade grade
Gleason sum

3+4=7 Second
Most most
common common Gleason
pattern pattern sum
Let’s revisit how we diagnosis prostate cancer
How do we diagnosis prostate cancer?

12 core biopsy

PSA 9 Prostate biopsy

T1 exam
44433444 33333344
Gleason 4 + 3 Gleason 3 + 4
Involving 50% of core Involving 25% of core

“…Mr. Jones was diagnosed with a PSA 9, clinical T1 prostate adenocarcinoma with 2 of 12
cores positive for up to Gleason 4+3 disease and core involvement ranging from 25-50%...”
Gleason scores and risk stratification
Low risk Intermediate risk High risk
3+3 5+5

6 7 8+
3+4 5+4
4+3 4+5
4+4
3+5
*NEW* Gleason Grade Groups (GGG)
Gleason Score Gleason Group
3+3 1
3+4 2
4+3 3
4+4, 3+5, 5+3 4
4+5, 5+4, 5+5 5
 7800 men
Gleason Grade Groups Johns Hopkins

Biochemical Free
Survival (BFS)

The new Gleason Grade Groups provide increased discrimination of Gleason Score 7 disease

Pierorazio PM et al. BJU Int 2013

Gleason group informs prognosis

Findings validated Epstein Jl et al. Eur Urol 2016

Recurrence-Free probability Leapman MS et al. Eur Urol 2016
There’s more than just Gleason score…

…PSA
…DRE
Risk stratification guides management

Gleason
PSA
score

Clinical
stage
Risk classification

Sathianathan NJ et al Nat Rev Urol 2018

CT and bone scan
Management
Localized disease
Recurrent disease
Metastatic hormone naïve prostate cancer
Metastatic castrate resistant prostate cancer (CRPC)
Management: localized prostate cancer
• Watchful waiting
• Active surveillance
• Surgery - radical prostatectomy
• External beam radiotherapy
• Brachytherapy
• Cryotherapy – localized disease/salvage
• HIFU- investigational/primary/salvage
• Primary hormonal therapy
Watchful waiting
• Expectant management
• No planned repeat biopsies
• Monitoring for the development of metastatic disease
• Reserve treatment (medical therapy) for if and when metastatic
disease develops
Active surveillance

Litwin M et al. JAMA 2017

Radical prostatectomy
Radical prostatectomy
Radical prostatectomy

Early complications Late complications

• Bleeding (transfusion) • Incontinence
• Infection • Impotence
• Bladder / ureteric injury
• Rectal injury
• Pelvic nerve damage
• Urine leak / urinoma
• Hematoma / lymphocele
• MI, stroke, DVT, PE, etc.
External beam radiotherapy
External beam radiotherapy
• Side effects
• Hematuria
• LUTS
• Hematochezia
• Diarrhea
• Skin irritation
• Fatigue
• Urethral or ureteric stricture disease
• Secondary malignancies
• Radiation cystitis
• Radiation proctitis
Brachytherapy
Management decision making
• Factors to consider:
• Life expectancy (age, co-morbidity)
• Prognostic factors (stage, grade, PSA, biopsy)
• Treatment effectiveness
• Complications rates, side effects of therapy

The endpoint of cancer treatment should be quality-adjusted survival, not survival at all costs
to the patient
Litwin M et al. JAMA 2017
• Population-based study
>32,000 pts
• Patients treated with surgery
or rads 2002-2009
• Measured the 5-year
cumulative incidence of
admissions, procedures

Nam RK et al Lancet 2014

Treatment trends

Martin JM et al. Cancer 2014

Hormone therapy
Mechanisms
of action

With initial LHRH agonist use, one can expect a “testosterone flair”. Thus, an anti-androgen (eg.
Bicalutamide) is used for a few weeks before receiving their ADT to prevent this occurrence.

Sharifi N et al JAMA 2015

ADT: Hypothalamus

Mechanism of action LHRH

Anterior Pituitary

ACTH LH

Adrenal gland Testis

5% 95%
Adrenal androgens Testosterone

Prostate
 Negative feedback

Hypothalamus

LHRH

Anterior Pituitary

ACTH LH

Adrenal gland Testis

5% 95%
Adrenal androgens Testosterone

Prostate
 - LHRH agonist
- Eligard

+
Hypothalamus - Zoladex

- LHRH
- Lupron

Anterior Pituitary

ACTH

Adrenal gland
+- LH

Testis

5%
Testosterone
+-
Prostate
95%
Testosterone
Goal of ADT:
Reduce testosterone to “castrate” levels

Klotz L et al. J Clin Oncol 2015

Indications for hormone therapy
• Metastatic disease
• With XRT for intermediate and high risk PCa
• For patients who have positive lymph nodes following RP

• For biochemical recurrence following primary treatment

• If PSA >0.2 ng/ml following radical prostatectomy
• If PSA is greater than nadir + 2 ng/ml following radiotherapy

• Primary treatment for PCa among those not fit for other treatments
• Cytoreduction (brachytherapy)
 PFS PCM OS

At 10 years, the XRT/ADT group prevailed

DFS was 47.7% (vs. 22.7%)
OS was 58.1% (vs. 39.8%)
PCM was 10.4% (vs. 30.4%)
There was no increase in cardiovascular-related mortality between groups
Bolla et al. Lancet 2010
98 men with node positive disease after RP
Randomized to hormone tx or observation

Median f/u 7.1 years

ADT has significant side effects
Management of advanced
prostate cancer
Metastatic hormone naïve prostate cancer

Metastatic Castrate resistant prostate cancer (CRPC)

2010
Natural history of (treated) prostate cancer
PSA
Hormone sensitive prostate cancer Castrate-resistant prostate cancer (CRPC)

Death

Local Chemo
therapy

ADT

Time
Surgery Eligard Docetaxel
Radiation Zoladex
Lupron
Degarelix
2020 - Natural history of (treated) prostate cancer
Apalutamide - TITAN
Enzalutamide - ENZAMET
Docetaxel
Abiraterone - LATITUDE

PSA mHSPC mCRPC

Hormone sensitive prostate cancer Death

Castrate-resistant prostate cancer (CRPC)
Post-chemo
medications
Chemo
Pre-chemo
Local
medications
therapy

ADT

Time
Surgery LHRH agonist M0 CRPC Abiraterone Docetaxel Abiraterone
Radiation LHRH antagonist Apalutamide Enzalutamide Enzalutamide
Enzalutamide Cabazitaxel
Darolutamide - ARAMIS Radium 223
(Sipuleucel T)
Thank you
jnayak@sbgh.mb.ca