Localized Prostate CancerHave we finally got it right?

Shingai Mutambirwa

Professor & Chair-Division Urology

DGMAH & SMU

Pretoria

SOUTH AFRICA

ESMO Cape Town 14 Feb 2018

Disclosures

Advisory boards/Lecturer/Consultant-

Aspen

Astellas

Astra-Zeneca

Bayer

Ferring

Lilly

Pfizer

Sanofi

The male reproductive system

Rectum

Urinary bladder

Prostate

Seminal vesicle

Epididymis

ScrotumTesticle

Penis

Urethra

Vas deferens

Incidence of cancer in males

Prostate

Lung

Colorectal

Bladder

Kidney-renal

Mouth Pharynx

Stomach

Percentage incidence of cancer in males.

Predicted increase in incidence

PROBABLY 50% DON’T NEED TREATMENT!

n over 65 years .

Worldwide variation in prostate cancer incidence rates

Rates per 100,000 population

1.2

6.6

7

23

40

44

50

60

102

0 20 40 60 80 100 120

China

India

Japan

UK

Switzerland

Norway

Sweden

US White

US Black

Diagnosis of prostate cancer

• The diagnosis of prostate cancer may

comprise three steps, incorporating a range

of diagnostic and imaging tests

– Early detection of prostate cancer is

performed through DRE and PSA testing

– TRUS-guided prostate biopsy is performed to

confirm the diagnosis and grade the tumour

– Imaging studies – CT, MRI and radionuclide

bone scan – may be conducted if metastases

are suspected

9

CT=computed tomography; DRE=digital rectal examination; MRI=magnetic resonance imaging; PSA=prostate-specific antigen;

TRUS=transrectal ultrasound.

American Cancer Society. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-diagnosis. Last accessed

June 2014.

Diagnosis

Impact of PSA screening on incidence and mortality

• The introduction of PSA screening

in the early 1990s has led to a rise

in the detection of prostate cancer

across Europe, particularly among

men aged

Prostate biopsy

• TRUS or a transperineal laterally-directed core

biopsy is the standard way to obtain material

for histopathology1

• A 10–12 core systematic biopsy targeting the

far lateral aspect of the peripheral zone is

standard practice for initial biopsy2

• The transrectal approach has limitations in

sampling the anterior regions of the gland2

• The transperineal approach employing a

mapping scheme, allows for more accurate

sampling of the entire gland2

• MRI-guided biopsy may be used to investigate

anterior located prostate cancer1

• Saturation biopsy is the preferred option after

initial negative sampling2

13

MRI=magnetic resonance imaging; TRUS=TransRectal UltraSound.

1. Heidenreich A, et al. Eur Urol 2011:59;61–71.

2. Dominguez-Escrig JL, et al. Prostate Cancer 2011;2011:386207.

Transrectal

Transperineal

Diagnosis

14

Clinical staging

Nx = loco-regional lymph nodes

cannot be evaluated

N0 = no lymph node involvement

N1-N3 = regional lymph metastasisN+

M+Mx = no metastasis can be

evaluated

M0 = no distant metastasis

M1 = distant metastasis present

1a = lymph nodes other than

regional nodes

1 b = skeletal

1c = other sites

D3 Resistant to hormonal therapy

Imaging techniques

• Radionuclide bone scan

– Used to determine spread of prostate cancer

to the bones

– A small amount of radioactive material is

injected into a vein and settles in damaged

areas of bone, viewed as ‘hot spots’ on

the skeleton

– Hot spots are suggestive of cancer in the

bone, but may also arise due to arthritis or

other bone diseases

– The detection of possible cancer needs to

be confirmed with other imaging tests such

as X-rays, CT or MRI scans

20

CT=computed tomography; MRI=magnetic resonance imaging.

ACS prostate cancer: Detailed guide. Available from: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-

cancer-diagnosis. Last accessed June 2014.

Characterising the tumour

Please see Module 3: CRPC and its treatment for further information on metastatic spread

Imaging techniques

• Computed tomography

– Combines X-rays and computer technology to give images

of the soft tissues and bones in the body1

– Can determine spread of cancer into the lymph nodes, or

other organs/structures1

– Not as useful as MRI for looking at the prostate gland itself1

– With addition of a radionucleotide tracer, PET-CT

is the preferred technique for recurrence detection2

• MRI/diffusion-weighted MRI

– Uses radio waves and strong magnets instead of

X-rays to produce 3D images of the prostate and show

whether the cancer has spread to nearby structures1

– MRI is the most accurate technique for staging cancer2

– Diffusion-weighted MRI detects free water diffusion: the

greater the density of tissues, e.g. tumours, the more water

restriction2

21

CT=computed tomography; MRI=magnetic resonance imaging; PET=positron emission tomography.

1. ACS prostate cancer: Detailed guide. Available from: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-

cancer-diagnosis. Last accessed June 2014.

2. Mayans AR, et al. Arch Esp Urol 2011;64:746–64.

Characterising the tumour

• Localised– Active Surveillence

– Curative

• Prostatectomy

• Radiotherapy

• HIFU/Cryo?

– Hormonal therapy?

• Locally advanced

– Watchful waiting

– Local control

• Hormonal therapy

• Radiotherapy

• Combinations

• Metastatic

– Palliation - Hormonal therapy

Treatment Options

Androgens & the prostate gland

Radical Prostatectomy-

Retropubic,Perineal,Laparoscopic

or Robotic?

Radiotherapy

EBRT (external beam radiation therapy)

Old EBRT(

Radical prostatectomy for localised/ locally

advanced prostate cancer

Epstein et al 1996

% patients

progression-

free

0

10

20

30

40

50

60

70

80

90

100

Localised Establishedcapsular

penetration

Seminalvesicle

invasion

Lymph nodemetastases

Focalcapsular

penetration

p

Focal therapy?

Conclusion

G 6 G7 (3+4) G7 (4+3) G8

G9/T3

Active

Surveillance

Whole

gland

treatment

Agressive

radical

treatmentSurgery + radiotherapy

Radiotherapy + hormonal

therapy

Today 170 000 new cases/year in the US, 343 000 in Europe

70 % undergo radical treatment

20% have active surveillance which can be stressful

Around 35% patient have overtreatment: they are the target for

focal therapy

Focal

treatment

10,000,000 men at risk

Death

34,000

CRPC

Fail

Local

Treatment

(30%)

ABI

Chemo

MDV-3100

Hormonal

Management

Local Therapy

Incidence

240,000

PET +/-MRI vs CT

Why are biomarkers needed for prostate cancer?

i) for reliable diagnosis of significant prostate cancer and making therapy decisions;

ii) for early prediction of prognosis of the future course of disease, which may lead to

adjusted monitoring and optimized therapy

iii) for prediction of therapy response and thus stratifying potential treatment benefit

iv) the identification of alternative therapeutic targets based on molecular analyses (eg.

target expression and mutational status)

v) developing individualized treatment options and thus improve patient outcomes

vi) standardization of study/cohort design, permitting standardized reporting

Organisation of Follow Up and Multidisciplinary

Uro-oncology Panel

Full Panel members•Urologist•Medical Oncologist•Radiologist•Radiotherapist

PatientUrologist Follow-

Up

Neuro-surgeon

Medical Oncologist

Follow-Up

Radio-therapist

Radio-logist

Additional:•Neurosurgeon•General Surgeon•Thoracic Surgeon•Pathologist