AUC Prostate Cancer Kuching August 2013

AUC Prostate Cancer
Kuching August 2013
Case Scenario 1: Issue of PSA and
biopsy strategy, re-biopsy
Cyril Natarajan
Case Scenario
• 62 y/o retired teacher has mild LUTs, a normal DRE
but PSA is 5.1 ng/ml
– A. He is worried about Pca. How would you counsel him?
– B. He agrees to undergo a TRUS/Bx. Describe the procedure
– C. Day 1 post-procedure he is admitted with fever & chills. How would you manage
him?
– D. HPE shows focal HGPIN in 1 core, but no Pca. What is PIN? What will you do
next?
– E. Next 2 consecutive PSA readings 6/12 apart are 6.2 & 6.4 respectively. What is
the PSA velocity? What is the trigger for a rpt biopsy?
– F. Rpt biopsy is performed. How would you do it differently from the 1st biopsy?
A. He is worried about PCa. How
would you counsel him?
• Full urological history
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LUTS
Age
Racial origin
Family history
History of UTI’s
Drug history
If advanced disease
» Bone pain/leg swelling/LOA/LOW/coagulopathy/recent
peripheral neurology
Examination
• General urological examination
– Abdominal examination
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•
•
•
Ballotable kidneys
Other abdominal mases
Hernial orifices
External genitalia; external meatus
• DRE
• Size, consistency, rectal mucosa, palpable nodules,
tenderness
Counseling
PSA counseling
• What is PSA?
• Significance of a raised PSA?
TRUS/Biopsy counseling
• Information about the procedure
• Efficacy of a TRUS/Bx with respect to PCa
• What next if the Bx is positive for PCa?
• Explanation about complications
PSA
• 34 kD serine protease (aka human kallikriene 3);
coded by a Chr 19 gene
• Secreted uniquely by prostatic ductal epithelium
• Biological effect is to liquefy semen
• 3 forms in serum
• Free
• Bound to ACT (α-1 antichymotrypsin)
• Bound to AMG (α-2 macrogloblulin)
• T ½ : 2 – 3/7
Conditions other than PCa with raised
PSA
Inflammation
Infection
BPH
Iatrogenic
• DRE
• Instrumentation
Ejaculation
Daily variation
• 20% (same as DRE and ejaculation)
Significance of a raised PSA
• Age- and race-specific PSA
• Osterling et al, JAMA 1993
• Race ranges added by Morgan et al
Predicting PCa from a PSA value
• No ‘normal’ PSA value
• PCa prevalence with PSA < 4ng/ml
PSA
Risk of PCa (prevalence)
Risk of GL > 7
0 – 0.5
6.6%
0.8%
0.6 - 1
10.1%
1.0%
1.1 - 2
17%
2.0%
2.1 - 3
23.9%
4.6%
3.1 - 4
26.9%
6.7%
– Thompson et al, NEJM 2004 (PCPT)
For PSA > 4ng/ml
Sensitivity
20%
Specificity
60 – 70%
Predicting PCa with PSA ranges
PSA
% of PCa (patients > 50yrs)
0-4
Not biopsied
4 - 10
26%
> 10
53%
Catalona et al, J Urol 1994
PSA range (ng/ml)
PPV
20 - 29
74%
30 - 39
90%
50 - 99
100%
> 20
87%
Gerstenbluth et al, J Urol 2002
Counseling for a TRUS/Bx
The procedure
• Explanation that core biopsies would be taken using a rectal U/S probe with LA
Efficacy
• 1st, 2nd, 3rd and 4th biopsies relating to Pca positivity of 22%, 10%, 5% and 4%
respectively
• Djavan et al, J Urol 2001
• Explanation that biopsies may need to be repeated if initially –ve
Further action if biopsies are +ve
• Active monitoring
• Radical treatment Radiotherapy or Surgery
Complications
•Haematospermia 37.4%
•Haematuria > 1/7 14.5%
•Rectal bleeding <2/7 2.2%
•Prostatitis
1.0%
•Fever > 38.5C
0.8%
•Epididymitis
0.7%
•Rectal bleeding > 2/7 0.7%
•Urnary retention
0.2%
•Other complications req. hospitalisation
0.3%
Post-procedure counseling
• To go to a nearest hospital if
• High fever +/- chills and rigors
– Telephone contact No. given to patient if he needs advice
• Severe bleeding
– Haematuria
– PR bleeding
• Increase fluid intake
• Avoid constipation
He agrees to undergo a TRUS/Bx.
Describe the procedure
– Need for prostate biopsies
• PSA level
• Suspicious DRE
• Other factors
» Biological age
» Potential co-morbidities (ASA Index & Charlson Comorbidity Index)
» Therapeutic consequences
• Risk stratification
• Roobol et al, Eur Urol 2010
• 1st elevated PSA should not prompt immediate Bx
» Should be verified after a few weeks
» Same assay
» Standardized conditions ie no non-PCa factors that can elevate PSA
• EAU 2013
TRUS/BX preparation
Fully informed and consented patient
Antibiotic prophylaxis
• Routine
• ‘Special’ situations eg prosthetic heart valves, valvular heart disease,
implants
Rectal preparation
Patients on anticoagulants
• Anti-platelets - Primary or Secondary prophylaxis ?
• Other anticoagulants eg warfarin
Antibiotic prophylaxis
• Wide variety of regimes
• Oral or i/v antibiotics state-of-the-art
• Types
– Quinolones drug of choice
• Ciprofloxacin superior to ofloxacin
» (EAU 2013) (LE 1B)
• Increased drug resistance to quinolones in recent yrs with rise of severe
infections post Bx
• bacteremia/sepsis can still occur in 0.1% to 0.5%
» (Djavan et al, 2001b ; Raaijmakers et al, 2002)
• patients at higher risk of developing endocarditis or infection of prosthetic
implants,
» iv ampicillin (vancomycin, if penicillin allergic) and gentamicin
• This patient:
– Oral Ciprofloxacin 500mg bd 2/7 prior and 3/7 post-Bx
Anticoagulant therapy
•
Primary prophylaxis
– Stop
Drug
Days of stoppage
Low-dose Asprin
5
Clopidogrel
7
Ticlodipine
14
•
Warfarin
• If high risk of thrombo-emoblic events
– ‘bridging’ therapy with heparin
• Stopped in all other patients
•
Secondary prophylaxis
– Continue anti-platelets
– Stop 2nd anti-platelet and continue ASA
•
Prospective studies on TRUS/Bx with continued low-dose ASA
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–
–
Maan Z et al, BJUI 2003
Rodriguez et al, J Urol 1998
Herget et al, Can Assoc Radiol J, 1999
Bowel preparation and positioning
• Bowels
– Bowel cleansing @ home with simple enema or PEG 1-3 days prior to
Bx’s
– Bisacodyl suppositories on the the night before Bx’s
• Positioning
• *Left lateral
• Buttocks as close to edge of couch as possible
• Knee-elbow
• Lithotomy
TRUS/Bx procedure
• Equipment
– 7.5MHz trans-rectal bi-directional probe
• Multi-planar views
– Spring-driven 18G needle core biopsy gun
– 22G 7-inch long spinal needle with 10cc syringe
– Lignocaine 2%, 5cc bilaterally
• peri-prostatic
• TRUS guidance along the biopsy channel of the transducer
• area between the seminal vesicles and apex of the prostate
Systematic scan
• DRE
– Rule out rectal pathology
– Identification of palpable abnormalities
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Measure gland volume
Scan in both planes , base to apex and side to side
Record images
Echotexture,nodules calcification,symmetry
Evaluate the capsule, SV and ED
CDI
TRUS – visibility of prostate cancer
PSA LEVEL
0–4
4 – 10
10 – 20
> 20
% with Trus lesion
15
30
40
75
TRUS – hypoechoic lesions
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•
•
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Prostate cancer
BPH
Ductal ectasia
Infarct
Prostatitis
PIN
Prostate biopsy – local anaesthesia
Prostate biopsy
painful in up to 96% patients
severe pain 20%
related to age and number of cores
1. Rectal lignocaine Chang J Urol 2001
2. Periprostatic lignocaine
pain reduction Nash et al J Urol 1996
Leibovici et al J Urol 2002
Patel et al BJU Int 2001
Pareek G et al, J Urol 2001
Anatomy
Transrectal biopsy - technique
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•
•
•
Guide visible on USS display
Sagittal plane
Choose site of biopsy and keep probe still
Insert needle through rectal wall until capsule
indents
• Fire gun and remove needle immediately
• Repeat.
• Minimum time in rectal wall, try not to biopsy
outside the gland
Increased cancer detection by directing more
biopsies into the lateral PZ
• Laterally directed sextant – reduce false negative rate
by 50%
• Sextant + 2 lat PZ - increased cancer detection
35% [ Eskew J Urol 1997]
14% [ Chang J Urol 1998]
• Sextant + 3 lat PZ – increased cancer detection
22% [ Beurton Br J Urol 1997]
Sites of Standard and Peripheral
Biopsy
Peyromaurie et al J Urol 2002
Biopsy strategies
No.
6
8
Adv.
Disadv
Ref.
established
30 – 50 % missed
Hodge et al 1989
improves diagnosis
Presti et al 2000
from 85 – 97%
10
improves diagnosis mainly lateral biopsies Ravery et al 1999
may be no better than 8
12
improves diagnosis
more bleeding
Brossner et al 2000
compared to 6 but ?8
>12 unproven
more complications Babiaan et al 2000
BIOPSY (EUA Guidelines 2013)
• On baseline biopsies, the sample sites should be as far
posterior and lateral in the peripheral gland as possible
• Additional cores should be obtained from suspected areas by
DRE/TRUS
• DRE-guided Bx’s
• Sextant biopsy is no longer considered adequate
• Gland volume 30 – 40 mls
• At least 8 cores
• The British Prostate Testing for Cancer and Treatment Study
has recommended 10-core biopsies
• Donovan et al, ProtecT Study group, Health Technol Assess 2003
• > 12 cores not significantly more conclusive
Targeted biopsy techniques
MRI and MR spectroscopy
• Reduced citrate and elevated choline levels in
cancer.
Scheidler et al Radiology 1999 213 47-480
• Improved cancer localisation
• Hricak, Radiology 1999
• T2 weighted MRI
• Kaji, Radiology 1998
• Accuracy increased 52 – 74%
• Specificity increased 26-65%
• ? Use in patients with negative biopsy or HGPIN
Handling of TRUS/Bx specimens
• Storage
– Bx’s from different sites in separate vials
– Processed in separate cassestes
– 18G needle used to lift cores in 10% buffered
formalin
Day 1 post-procedure he is admitted with fever
& chills. How would you manage him?
Unstable patient with urosepsis/severe sepsis/septic shock/SIRS
• Immediate resuscitation (ABC)
• ICU
• I/V fluids Hartmans, Colloids
• Inotropes, eg Noradrenaline
• Antibiotics: Empirical eg Carbapenams, Broad spectrum Cephalosporins, +/aminoglycosides
• Full septic work-up
• CBD
Stable patient
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Admit
Change oral antibiotics to I/V B/spectrum Cephalosporins/ Carbapenams
Full septic work-up
CBD
Close monitoring
HPE shows focal HGPIN in 1 core, but no Pca. What is
PIN? What will you do next?
• PIN
– Prostate Intraepithelial Neoplasia
– Precursor of invasive carcinoma
• Precedes cancer by 10 years,
• 70% will have PCa by 80 years
– Does not secrete PSA
HPE shows focal HGPIN in 1 core, but no Pca. What is
PIN? What will you do next?
• In this patient no indication for re-Bx as only 1 core
involved
• EAU 2013 (Moore CK et al, J Urol 2005) LE: 2A
• only a slightly increased Pca risk (23% to 24%)
compared to an initial benign Bx (20%)
• F/U needed with serial DRE and PSA
• Indications for re-Bx
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•
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Suspicious DRE
Rising and/or persistently high PSA
ASAP
Extensive (Multiple Bx sites) HGPIN
Next 2 consecutive PSA readings 6/12 apart are 6.2 &
6.4 respectively. What is the PSA velocity? What is the
trigger for a rpt biopsy?
• PSA velocity
– The rise in PSA per year in ng/ml/yr
– > 0.75ng/ml/yr assoc. with an increased PCa risk (Carter HB et al,
JAMA 1992)
– > 0.6 ng/ml/yr (Sun et al, BJUI 2007)
– PSAV = 0.5 x (PSA2 – PSA1/T1 + PSA3 – PSA2/T2)
• T = Time in yrs
• PSAV in this patient
– = 0.5 x (6.2 – 5.1/0.5 + 6.4 – 6.2/0.5)
– = 1.3 ng/ml/yr
• Trigger for rpt Bx:
– > 0.75 ng/ml/yr
– Abnormal DRE
Rpt biopsy is performed. How would you
do it differently from the 1st biopsy?
• 2nd TRUS/Bx
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–
–
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Transistion zone Bx’s
End-firing probe for TZ Bx’s
Take 10 to 12 cores if initial cores were not adequate
Anterior zone biopsies (transperineal)
• Other possible options for re-TRUS/Bx
– Saturation Bx’s
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20 cores
PCa detection 30 – 43% (depends on no. of previous Bx cores)
Can be done transperineally (additional 38% PCa detected
10% AUR
Thank You
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