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Investigation and Management of
Prostate Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Edith Cavell Hospital, Peterborough
Investigation and Management of Prostate
How Prostate Cancer Presents
Examination of the Patient
Investigations, including PSA
Screening for Prostate Cancer
The Staging of Prostate Cancer
The Management of Prostate Cancer
– Disease confined to the Prostate
– Locally Advanced Disease
– Metastatic Disease
• Complications of Prostate Cancer
• Palliative Care
How Prostate Cancer Presents
• Disease confined to the prostate
– There are no SPECIFIC symptoms of early stage
prostate cancer
– The symptoms are therefore the same as those
of BPH
Poor / intermittent urinary flow
Terminal Dribbling
Nocturia / Frequency
How Prostate Cancer Presents
• Locally Advanced Prostate Cancer
– Cancer may invade the trigone and ureters
causing ureteric obstruction
– Bleeding
– Pelvic Pain
– Worsening of voiding symptoms
How Prostate Cancer Presents
• Metastatic Prostate Cancer
Pain from bone metastases
Spinal cord compression
Pathological fractures
Poor general health / malaise
Examination of the Patient
• General Examination
Abdominal distension
?Palpable bladder
DRE (Digital rectal examination) of the Prostate
• Haematological
– FBC, Creatinine, LFTs
• Consider need for Transrectal Ultrasound
and biopsy of the Prostate (TRUS and
• Isotope bone scan – not indicated in
asymptomatic patient with PSA <10ng/ml
• CT / MRI
The Role of PSA
• Single-chain glycoprotein of 240 amino acid
residues and 4 carbohydrate side chains
• Physiologic function is lysis of the seminal
• Has a half-life of 2.2 days
• Prostate specific, but not-cancer specific
• Should not be used indiscriminately
Prostate Specific Antigen
• In addition to Prostate cancer, an
elevated level may be found with
Increasing age
Acute urinary retention and Catheterisation
Prostate biopsy
but NOT rectal examination
The Problem with PSA
• Men with Prostate cancer may have a
normal PSA
• Men with BPH or other benign
conditions may have a raised PSA
• No longer thought to be prostatespecific
• What to do with men with PSA in the
range 4-10 ng/ml?
Refinements in the use of PSA
• Refinements theoretically most useful
when PSA between 4-10 ng/ml
• Below 4ng/ml prevalence of CAP ~
1.4%, above 10ng/ml prevalence rises
to 53.3%
• PSA Density
• PSA Velocity
• Age-Specific PSA
• Free vs. total PSA
Age Specific PSA Ranges
• Determined from evaluation of PSA
values and prostate volumes according
to age
• Age specific ranges make PSA a more
sensitive marker for men <60yrs, and
more specific in men > 60 yrs
Age Specific Reference Ranges
40 - 49
50 - 59
60 - 69
70 - 79
<= 2.5
<= 3.5
<= 4.5
<= 6.5
Free versus Total PSA
• The majority of PSA in serum is bound to
alpha-1-antichymotrypsin (ACT)
• The proportion of free to total PSA is
significantly lower in CAP
• Not yet understood why this ratio changes in
• May be a way of discriminating patients with
BPH and those with CAP
Free versus Total PSA
• Choice of ratio cut-off remains to be decided
- balance between missing some cancers
and dramatically reducing the number of
• The Free to Total (F/T) PSA Ratio is perhaps
best reserved for difficult diagnostic cases;
for example men with a PSA between 410ng/ml, or those who have previously had
a negative biopsy
Free versus Total PSA
• For men with PSA 4-10ng / ml and
% free PSA Probability of cancer %
Screening for Prostate cancer
The Case For:
• In order to hope to cure a patient the
disease must be diagnosed when it is organ
• The incidence of prostate cancer is rising by
3% per year
• Prostate cancer is now the second
commonest cause of death in men in
Northern Europe
Screening for Prostate cancer
The case against
• Transrectal ultrasound and biopsy has a
morbidity rate
• Negative biopsies lead to significant
patient anxiety
• Correct protocol has not yet been
• May detect only incurable disease, or
small tumours that are clinically
unimportant (but…)
Cancers that are PSA detected
• have been shown to be clinically significant
• are frequently poorly differentiated or spread
widely throughout the prostate
• when removed by radical surgery will often
be upgraded or upstaged.
Current opinion about screening?
• Remains divided
• Support for screening for prostate cancer is
growing among eminent urologists
(admittedly, those with an interest in prostate
The Staging of Prostate Cancer
• TNM System
• Gleason score
TNM Staging of Prostate Cancer
• T1 – Impalpable / Not visible on TRUS
– T1a: <5% of TURP chips
– T1b: >5% of TURP chips
– T1c: Detected on Prostate biopsy
Confined to
• T2 – Palpable OR visible on TRUS, but
confined to prostate
– T2a: Tumour in one lobe
– T2b: Tumour in both lobes
• T3 – Extends beyond the boundary of the
• T4 – Fixed to other organs (e.g. bladder)
• M0/M1 – No Metastases / Metastases
Locally advanced
Gleason Score
• Pathologist looks at two most common
histological patterns under microscope
• Gives each a score from 1-5
• 1=Well differentiated ………. 5=Poorly
• Gleason score expressed as “Gleason X+Y”
(e.g. Gleason 4+3)
• Total Gleason sum score can also be
expressed (e.g. Gleason 7 if using above
Management of Prostate Cancer
confined to prostate
• Four options
Watchful waiting
Radical Prostatectomy
Radical Radiotherapy (including brachytherapy)
(Hormones – See Metastatic disease)
Watchful Waiting
• Based on the results of autopsy studies
• Many men die with prostate cancer rather
than from it
• Usual Indications
– Stage T1a disease and well/moderately
differentiated tumours and life expectancy > 10
– Stage T1b-T2b: Patients with life expectancy <
10 years and asymptomatic
Radical Prostatectomy
• Surgical excision of whole of
Prostate/Seminal vesicles
• Relatively low morbidity procedure in most
• Patient discharged home in 5-7 days
• Trial without catheter at approx 14 days
Complications of Radical Prostatectomy
Management of Prostate Cancer Radiotherapy
• Radiation therapy may produce treatment results
comparable to those achieved by Radical
• NO randomised studies comparing radical
radiotherapy, radical prostatectomy, and watchful
waiting have been performed
• Similar local control rates, and 10 year disease-free
survival rates to radical prostatectomy
• Good “free from PSA failure” rates
• Similar Complication rates to Radical Prostatectomy
• Bowel symptoms common during treatment
Management of Prostate Cancer Brachytherapy
• Interstitial radiation therapy (brachytherapy)
appears to be making a comeback
• Involves implantation of permanent
radioactive seeds into prostate
• Complication rates far less than for external
beam radiotherapy
• Not suitable for patients with significant
voiding symptoms
Choice of Therapy?
• Patient choice after:
– Full counselling by surgeon and oncologist
– All questions answered
• Partin’s tables can be helpful
Partins Tables
The Management of Locally Advanced
Prostate Cancer
• Cancer outside of prostate (by definition) so
radical prostatectomy will not be curative
• External beam Radiotherapy is an option
• Hormonal Therapy – Casodex
(Bicalutamide) – may be helpful
Management of Metastatic Prostate
• The mainstay of treatment of metastatic
disease is Anti-androgens, LHRH agonist, or
• Maximal androgen blockade has not proved
of benefit for the majority of patients
• Intermittent androgen blockade may be of
benefit for selected patients, but the longterm durability and advantages are not clear
at present
Management of Metastatic Disease –
Hormonal Therapy
• Options
– Antiandrogens (e.g. Cyproterone Acetate)
– LHRH agonists (e.g. Zoladex, Prostap)
– Subcapsular orchidectomy
• Must ALWAYS start with an antiandrogen
– Potential spinal cord compression
– Pathological fracture
• Assess clinical response
• Patient may then opt to stay on CPA, or try
Zoladex or Orchidectomy
Management of Metastatic Disease
• Median duration of clinical / PSA response is
24 months
• Eventually disease becomes hormone
Complications of Prostate Cancer
• Pathological Fracture
– Prostate cancer may present de novo with
pathological fracture
– Can be anticipated in some cases
– Pain on weight bearing may herald pathological
– Prophylactic pinning of bone may be required
Complications of Prostate Cancer
• Spinal Cord Compression
– May present de novo
– Can present with numbness/paraesthesiae, “off legs”,
“falls”, urinary difficulty
– Prevention is better than cure – function once lost is rarely
– Treatment
Admit for bed rest
high dose prednisone
Urgent MRI of Spine
Admission to radiotherapy centre for DXT
Start hormone therapy if patient NOT already on hormones
Palliation of advanced symptoms
• Pain from bone metastases - radiotherapy / steroids
• Pain from locally advanced disease - radiotherapy
• Lymphoedema of leg / DVT from pelvic nodal
disease - radiotherapy
• Ureteric obstruction - radiotherapy +/- stent or
• Voiding dysfunction - “channel” TURP
• Blood transfusion for anaemia