Download Investigation and Management of Prostate Cancer

Investigation and Management of
Prostate Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Edith Cavell Hospital, Peterborough
Investigation and Management of Prostate
Cancer
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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
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Hesitance
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
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Pain from bone metastases
Spinal cord compression
Pathological fractures
Poor general health / malaise
Examination of the Patient
• General Examination
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?Anaemic
Abdominal distension
?Palpable bladder
DRE (Digital rectal examination) of the Prostate
Investigation
• Haematological
– FBC, Creatinine, LFTs
– PSA
• Consider need for Transrectal Ultrasound
and biopsy of the Prostate (TRUS and
biopsy)
• 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
coagulum
• 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
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Increasing age
Acute urinary retention and Catheterisation
TURP
Prostatitis
Prostate biopsy
BPH
Ejaculation
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
Age
40 - 49
50 - 59
60 - 69
70 - 79
PSA
<= 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
CAP
• 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
biopsies
• 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 %
0-10
56
10-15
15-20
20-25
>25
28
20
16
8
Screening for Prostate cancer
The Case For:
• In order to hope to cure a patient the
disease must be diagnosed when it is organ
confined
• 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
defined
• 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
cancer)
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
Prostate
• T2 – Palpable OR visible on TRUS, but
confined to prostate
– T2a: Tumour in one lobe
– T2b: Tumour in both lobes
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• T3 – Extends beyond the boundary of the
prostate
• T4 – Fixed to other organs (e.g. bladder)
• M0/M1 – No Metastases / Metastases
Locally advanced
Metastatic
Gleason Score
• Pathologist looks at two most common
histological patterns under microscope
• Gives each a score from 1-5
• 1=Well differentiated ………. 5=Poorly
differentiated
• 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
example)
Management of Prostate Cancer
confined to prostate
• Four options
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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
years
– 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
series
• 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
Prostatectomy
• 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
Cancer
• The mainstay of treatment of metastatic
disease is Anti-androgens, LHRH agonist, or
Orchidectomy
• 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
unresponsive
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
fracture
– 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
regained
– Treatment
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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
nephrostomy
• Voiding dysfunction - “channel” TURP
• Blood transfusion for anaemia