The Big Four - Prostate Ca OLD

The Big Four: Prostate Cancer
Dr Ann Henry
Associate Professor in Clinical Oncology
University of Leeds and Leeds Cancer Centre
Leeds Institute of Cancer and Pathology

Radiation Therapeutics
Prostate Cancer

Anatomy
Coronal pelvic MR scan
Prostate gland function: To make seminal fluid

which is then stored in seminal vesicles
Presentation
• PSA Screening
– No official screening programme as no evidence yet that benefits
outweigh harms
– Men over 50 can request test but should also be given written
information
(https://www.gov.uk/government/uploads/system/uploads/attachment
_data/file/509191/Patient_info_sheet.pdf)
• Urinary symptoms
– Reduced flow, frequency, nocturia
– Often due to co-existing BPH
• Symptoms of metastatic cancer
– Anaemia, bone pain, weight loss, general malaise

Impact of PSA Screening
PSA testing unreliable

May find slow growing cancer that never needed treatment
Risks over –diagnosis and over-treatment
PROTECT study outcomes
• Large UK randomised trial recently published NEJM

• Screen detected men with localised PCa aged 50-69
• Mean age 62 years, 77% Gleason 6, 76% T1c
• AM: Aims to avoid over treatment whilst maintaining ‘window
of curability’
• Randomised to one of three arms (>500 men in each arm)
– Radical prostatectomy
– Radical radiotherapy (74Gy 3D CRT with 6 months HT)
– Active monitoring with treatment indicated with PSA

PROTECT 10 year outcomes
• No difference on overall survival between arms (primary

endpoint)
• Survival much better than expected with 1% prostate cancer
related death and 10% all cause
• In active monitoring arm many will undergo radical treatment
• 25% at 3 years
• 54.8% at 10 years
• More metastatic cancer develops in those under AM and
radical treatment provides 50% reduction
• 33 men in AM arm
• 13 men in prostatectomy arm
• 16 men in radical RT arm
PROTECT impact
• To avoid 1 man developing metastatic prostate

cancer
– 27 men need to undergo prostatectomy
– 33 men need to undergo RT
• Prevent 1 man developing clinical progression
- 9 men need to undergo radical treatment
• Older men with co-morbidity potentially less benefit
with radical treatment

Clinical case
• Mr AB is a 60 year old man, • What would you advise?

previously fit and healthy, who
has recently started a new
relationship
• His new partner is aware of risk
of prostate cancer as her father
was diagnosed and treated in his
70’s (died of other causes)
• He attends GP Practice
requesting prostate cancer test

Clinical case
• Following discussion he opts to have PSA check

• PSA found to be elevated at 14ng/mL
• Referred within 2 week wait to urology team
• In urology clinic
– Any urinary symptoms
– Sexual and bowel function
– Any other co-morbidity
– Digital rectal examination
• Referred on to have a pre-biopsy MR scan
– Shows abnormality in right side of prostate
• Followed by trans-rectal US biopsy

TRUS biopsy
• Done as OP procedure
• Risks include
– Rectal discomfort for few
days/weeks
– Blood in urine or semen
– Urine infection with 3%
risk of sepsis requiring
hospitalisation

Gleason Grading
• Histological cancer grading

system for prostate
adenocarcinoma
• Major and minor tissue
architecture and gland formation
Graded 2-5 and then added
together
• Gleason 3+3 (6) Low grade
• Grade 3+4 or 4+3 (7)
Intermediate grade
• Grade 4+4 (8), 4+5 and 5+4 (9),
5+5 High grade and more
aggressive

Staging Prostate Cancer
T1: no palpable or visible cancer (on bx only)

T2: Cancer within prostate
T3: Cancer breaching prostate capsule
T4: Cancer growing into rectum or bladder
N0: No nodes N1: Nodes
M0: No mets M1: Mets

Risk groups
• Low Risk
– T1c/T2a, GS≤6, PSA≤10
• Intermediate Risk
– T2b/c or GS=7 or PSA10-20
• High Risk
– GS≥8 or PSA≥20

Clinical case
• Biopsy shows Gleason

4+3 prostate cancer on
the right
• Bone scan normal
• Staged as T2N0M0 and
intermediate risk
• Treatment advised
• Number of options
– Surgery
– Radiotherapy
Robotic prostatectomy
Robotic controlled ports Surgeon at console

• Example of VMAT delivery
• Volumetric Modulated Arc
Therapy
• RT delivered in arc around
patient
• Advantage is much shorter
treatment times of 2-3 minutes
compared to IMRT

Prostate brachytherapy
TRUS images acquired using

stepper unit, planned then
treatment delivered by
connecting to HDR machine

HDR plan boosting DiL

Which treatment?
• Surgery
– Good option for men aged < 70 with no co-morbidity
– Risks of long term incontinence and impotence
• Radiotherapy
– Non-invasive and good option in older or those with co-morbidity
– Risks of long term bowel problems
• Brachytherapy
– Good option in fit men with no-comorbidity
– Avoid in men with large prostates or significant urinary symtpoms

Advanced prostate cancer
• Presents with bone pain and

general malaise
• Bone scan shows widespread
mets around axial skeleton
• X-ray shows classic sclerotic
mets
• Androgen deprivation therapy
is main treatment
• Consider other systemic drugs
in addition in fit patients
– Chemotherapy
– Abiaterone/enzalutamide
• Palliative radiotherapy for
persistent bony pain
ADT adverse events
• Hot flushes
• Sexual function/shrinkage penis and testes
• Loss muscle bulk and strength
• Memory effects and mood disturbance
• The Lancet 2016 388, DOI:
10% weight gain and higher risk DM
(10.1016/S0140-
• Osteoporosis/higher fracture risk 6736(16)00583-3)
Cardiovascular risks
• Observational population studies suggest ADT

associated with 15-12% increase in CV mortality
• Events often occur early (first 12 months)
• Also increases in risk of stroke and PVD
• Some studies suggest those with pre-existing CV
disease at highest risk
• Lack of testosterone causes progression of
atherosclerosis
• Also metabolic syndrome with obesity, altered lipids and
increased risk DM

Metastatic spinal cord
compression
• Urgent referral to Specialist

Cancer Centre
• Consider surgery in younger, fit,
mobile patients with limited
metastatic disease
• High dose steroids
• Majority treated with palliative
XRT given as single or 5
fractions (within 24 hours of
diagnosis)
• If mobile 85% will walk after
treatment
• If paraplegic <15% will regain
some function

Summary
• Prostate cancer commonest cancer in men with incidence

that continues to rise
• Proportion of men with low/intermediate risk localised
disease can be managed with surveillance
• Surgery, radiation and ADT mainstay of curative treatments
• Increasing use of more systemic agents for advanced cancer
• The management of men dying with metastatic prostate
cancer can be challenging and should be good links between
primary/hospital and palliative care services.


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The Big Four: Prostate Cancer

Leeds Institute of Cancer and Pathology

Leeds Institute of Cancer and Pathology

Coronal pelvic MR scan

Prostate gland function: To make seminal fluid

Leeds Institute of Cancer and Pathology

PSA testing unreliable

• Large UK randomised trial recently published NEJM

Leeds Institute of Cancer and Pathology

• No difference on overall survival between arms (primary

• To avoid 1 man developing metastatic prostate

Leeds Institute of Cancer and Pathology

• Mr AB is a 60 year old man, • What would you advise?

Leeds Institute of Cancer and Pathology

• Following discussion he opts to have PSA check

Leeds Institute of Cancer and Pathology

Leeds Institute of Cancer and Pathology

• Histological cancer grading

Leeds Institute of Cancer and Pathology

T1: no palpable or visible cancer (on bx only)

N0: No nodes N1: Nodes

M0: No mets M1: Mets

Leeds Institute of Cancer and Pathology

• Biopsy shows Gleason

Robotic controlled ports Surgeon at console

Leeds Institute of Cancer and Pathology

Leeds Institute of Cancer and Pathology

TRUS images acquired using

Leeds Institute of Cancer and Pathology

Leeds Institute of Cancer and Pathology

Leeds Institute of Cancer and Pathology

• Presents with bone pain and

• Observational population studies suggest ADT

Leeds Institute of Cancer and Pathology

• Urgent referral to Specialist

Leeds Institute of Cancer and Pathology

• Prostate cancer commonest cancer in men with incidence

Leeds Institute of Cancer and Pathology

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