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Prostate carcinoma- Prostate biopsy
1. PROSTATE BIOPSY
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1
2. Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2
3. Introduction
• TRUS of the prostate was first described by Watanabe
and colleagues in 1968.
• Till 1980s, digitally directed prostate biopsy were
common.
• Later replaced by TRUS directed prostate biopsies-
Considered the current standard of care.
3
Dept of Urology, GRH and KMC, Chennai.
5. Transperineal Biopsy- Open
• Introduced by Young in 1922.
• Involved transverse incision in the perineum between the
ischial tuberosities.
• 95% accurate.
• Risks: Urinary incontinence and erectile dysfunction were
present.
• Required a general anaesthetic and a week of
hospitalization
5
Dept of Urology, GRH and KMC, Chennai.
6. Transperineal Biopsy-Open
• Open perineal biopsy -
The earliest method of
collecting prostatic
tissue.
• It was once considered
the most accurate
technique.
6
Dept of Urology, GRH and KMC, Chennai.
7. Transperineal Needle Biopsy
• Barringer 1922
• Screw tip Needle
• Finger in the rectum
• Needle screwed through
perineum.
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Dept of Urology, GRH and KMC, Chennai.
13. Prostate sonography
• Prostate lies between the bladder neck and the
urogenital diaphragm, just anterior the rectum.
• The typical pathological zones of prostate are not visible
in TRUS.
• Corpora amylacea highlight the plane between the TZ
and CZ.
• Distended urethral lumen - hypoechoic appearance,
periurethral calcifications may produce thin echogenic
outline.
• Internal sphincter may be visualized sonographically as a
hypoechoic ring around the upper prostatic urethra.
13
Dept of Urology, GRH and KMC, Chennai.
15. Need for Biopsy
Based on :
• PSA level and/or
• DRE finding and/or
• Imaging
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Dept of Urology, GRH and KMC, Chennai.
16. Factors to consider beforehand
• Overall health,
• Age of the patient,
• Family history,
• Therapeutic options,
• Wishes of the patient and
• Other risk factors.
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Dept of Urology, GRH and KMC, Chennai.
17. Prostate cancer- Elevated risk
• Men older than 50 years of age
• Have family history of prostate cancer and more than 45
years
• African American men
• Men with PSA level greater than 1 ng/ml at 40 years and
greater than 2 ng at 60 years.
17
Dept of Urology, GRH and KMC, Chennai.
18. PSA Threshold for Biopsy
• Historically, it is recommended to do prostate biopsy if
serum PSA is > 4.0 ng/ml.
• Prostate Cancer Prevention Trial- There is no safe PSA
threshold that can rule out prostate cancer in any age
range.
• 15% had prostate cancer when PSA was < 4 ng/ml.
18
Dept of Urology, GRH and KMC, Chennai.
19. Prostate Biopsy-Indications
• Positive digital rectal examination regardless of PSA level
• PSA 4 to 10 ng/ml based on the patient risk benefit.
• PSA levels 2.5 ng/mL or less and PSA velocity 0.35 ng/mL
or greater per year.
• PSA level 2.6 to 4.0 ng/mL
• PSA level 4.0 ng/mL or greater especially if free PSA level
is 10% or less
19
Dept of Urology, GRH and KMC, Chennai.
23. Limited PSA Elevation
• Limited PSA elevation alone should not prompt
immediate biopsy.
• Prostate specific antigen level should be verified after a
few weeks, in the same laboratory, using the same assay
under standardised conditions (i.e. no ejaculation,
manipulations, and urinary tract infections [UTIs])
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Dept of Urology, GRH and KMC, Chennai.
24. Repeat Biopsy-Indications
• Rising and/or persistently elevated PSA
• Atypical small acinar proliferation (40% cancer risk)
• Extensive (multiple biopsy sites) with PIN (20%-30%
cancer risk) (NOTE: isolated high-grade PIN is no longer
considered an indication for repeat biopsy)
• Positive urinary PCA3 or other newer genomic tests such
as Confirm MDx* methylation assay
• Suspicious lesion on prostate magnetic resonance
imaging
• Differentiate local recurrence versus systemic disease
with PSA recurrence after local ablative therapy
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Dept of Urology, GRH and KMC, Chennai.
26. mpMRI and Prostate Biopsy
Controversies and Current Status
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Dept of Urology, GRH and KMC, Chennai.
27. PROMIS Study-2017
Aim:
Multi-parametric magnetic resonance imaging (MP-MRI)
used as a triage test might allow men to avoid
unnecessary TRUS-biopsy and improve diagnostic
accuracy.
27
Dept of Urology, GRH and KMC, Chennai.
28. PROMIS Study-2017
Conclusion:
• TRUS-biopsy performs poorly as a diagnostic test for
clinically significant prostate cancer.
• MP-MRI, used as a triage test before first prostate biopsy,
could identify a quarter of men who might safely avoid
an unnecessary biopsy and might improve the detection
of clinically significant cancer.
28
Dept of Urology, GRH and KMC, Chennai.
29. PRECISION Trial 2018
Aim:
MP MRI, with or without targeted biopsy, is an
alternative to standard TRUS guided biopsy for prostate-
cancer detection in men with a raised prostate-specific
antigen level who have not undergone biopsy.
However, comparative evidence is limited.
29
Dept of Urology, GRH and KMC, Chennai.
30. PRECISION Trial 2018
Conclusion:
A diagnostic pathway including risk assessment with MRI
before biopsy and MRI-targeted biopsy in the presence of
a lesion suggestive of cancer was superior to the
diagnostic pathway of standard transrectal
ultrasonography–guided biopsy.
30
Dept of Urology, GRH and KMC, Chennai.
32. MRI-FIRST Trial-2019
Aim:
Whether multiparametric MRI improves the detection of
clinically significant prostate cancer and avoids the need
for systematic biopsy in biopsy-naive patients remains
controversial.
Aim is to investigate whether using this approach before
biopsy would improve detection of clinically significant
prostate cancer in biopsy-naive patients.
32
Dept of Urology, GRH and KMC, Chennai.
33. MRI-FIRST Trial-2019
Conclusion:
Obtaining a multiparametric MRI before biopsy in biopsy-
naive patients can improve the detection of clinically
significant prostate cancer but does not seem to avoid
the need for systematic biopsy.
33
Dept of Urology, GRH and KMC, Chennai.
39. Patient Preparation
• Informed consent.
• Herbal supplements should be discontinued.
• Low dose aspirin need not be discontinued.
• Anticoagulant therapy (Warfarin, Clopidogrel etc) should
be stopped 7-10 days before the procedure.
• Novel oral anticoagulants apixaban, dabigatran and
rivaroxaban are stopped 2-5 days before the procedure.
• High risk thromboembolism on anticoagulation- Bridge
with unfractionated heparin.
39
Dept of Urology, GRH and KMC, Chennai.
40. Antibiotic Prophylaxis
• Recommended for all patients undergoing prostate
biopsy, irrespective of risk factors.
• No definitive evidence for superiority of longer course or
multiple doses compared to a shorter course or single
any dose protocols.
• Increasing resistance to fluoroquinolones, recent interest
in rectal swab culture before biopsy. (Not cost effective).
40
Dept of Urology, GRH and KMC, Chennai.
42. Cleansing Enema
• Home self administered enema before biopsy is
recommended.
• Decreases the amount of feces in the rectum - Produces
a superior acoustic window for prostate imaging.
• Its effect on reducing infection is debatable.
42
Dept of Urology, GRH and KMC, Chennai.
43. Patient Positioning
• Left lateral decubitus position with knees and hips flexed
at 90 degrees.
• Arm board attached parallel to the table and pillow
between the knees helps maintain the position.
• Buttocks should be flush with the end of the table to
allow manipulation.
• Right lateral decubitus or lithotomy position can also be
used.
• Lithotomy position is preferred in transperineal biopsies
43
Dept of Urology, GRH and KMC, Chennai.
44. Anesthesia
• Recommendation: TRUS guided infiltration anaesthesia
near the nerve bundles with local anaesthetic.
• 1-2% lignocaine using a long spinal needle (7 inch 22
gauge) and TRUS guidance along the biopsy channel of
the transducer.
• Volume - 5-10 ml.
• For saturation biopsy, 22 ml of lignocaine may be
needed.
• Intraprostatic injection can augment the anesthetic effect
seen with periprostatic injection.
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Dept of Urology, GRH and KMC, Chennai.
45. Topical Anaesthesia
• Intrarectal topical anaesthesia with local anaesthetic is
inferior and not recommended.
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Dept of Urology, GRH and KMC, Chennai.
46. Procedure
• Initial digital rectal examination should be performed.
• Prostate volume is determined.
• Imaging in sagittal and transverse planes is done.
• Examination starts at the base and ends in the apex.
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Dept of Urology, GRH and KMC, Chennai.
47. Suspicious Lesion
The lesion is identified.
Lesion is characterized regarding:
• Echogenicity (hypoechoic / hyperechoic)
• Calcifications,
• Contour abnormalities and
• Cystic nature.
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Dept of Urology, GRH and KMC, Chennai.
48. Biopsy Gun and Probe
• A spring driven 18 gauge needle core biopsy gun is most
often used.
• Biopsy needle path is better in the sagittal plane.
• Biopsy gun advances the needle 0.5 cm and samples the
subsequent 1.5 cm of tissue with the tip extending 0.5
cm beyond the area sampled.
• High frequency probe of 7 MHz is used for TRUS.
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Dept of Urology, GRH and KMC, Chennai.
49. Sextant Biopsy
• One core from the base, mid and apex bilaterally.
• Vast majority of the adenocarcinomas arise in
posterolateral PZ resulting in false negative results.
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Dept of Urology, GRH and KMC, Chennai.
50. Extended core biopsy techniques
• Current recommendation- Six cores are inadequate for
cancer detection.
• 12 core systematic biopsy that incorporates the apical
and far lateral cores is needed.
• Saturation biopsy 18-21 cores. (Average 21.5 cores)
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Dept of Urology, GRH and KMC, Chennai.
52. Repeat and Saturation Biopsies
• Patient has elevated PSA value or abnormal digital
examination with one or more negative prostate
biopsies.
• Second prostate biopsy in cases of negative finding on
initial biopsy is justified if concern about undetected
cancer persists.
• 3rd and 4th biopsies should be obtained only in selected
patients with high suspicion for cancer and /or poor
prognostic factors on the first or second biopsy.
52
Dept of Urology, GRH and KMC, Chennai.
53. Risks and Complications
• Incidence of serious complications (<1%)
• Bacterial infection
• Hematospermia
• Hematuria
• Rectal bleeding
• Prostatitis
• Fever greater than 101.3 degree
• Epididymitis
• Urinary retention
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Dept of Urology, GRH and KMC, Chennai.
54. Post Biopsy Infections
• Hospitalisation after prostate biopsy 0.6% to 4.1%.
• Any patient with complaining of fever after biopsy should
be assessed for the presence of sepsis.
• Main cause: Fluroquinolone resistant fecal bacteria.
• Predominant organism: E.coli
• Susceptibility: Second and third generation
cephalosporins, amikacin and carbapenams.
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Dept of Urology, GRH and KMC, Chennai.
55. Post Biopsy Infection-Risk factors
• Non white race
• Increased number of comorbidities
• Diabetes
• Prostate enlargement
• Foreign travel
• Recent antibiotic use.
• Number of previous biopsies.
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Dept of Urology, GRH and KMC, Chennai.
56. Bleeding
Incidence 23-63% of patients.
Control measures:
• Direct pressure by probe or digitally.
• Rectal tamponade using inflated condom
• Anoscopy and colonoscopy with injection of epinephrine
and polidocanol
• Angiography with embolisation
• Transrectal exploration and suturing
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Dept of Urology, GRH and KMC, Chennai.
58. Other complications
1. Vasovagal response 1.4 – 5.3%.
• Terminate the procedure
• Trendelenberg position and infusing IV fluids
2. Acute urinary retention leading to temporary
catheterization (0.2-0.4%)
3. Erectile dysfunction (controversial)
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Dept of Urology, GRH and KMC, Chennai.
60. Transperineal Prostate Biopsy
• Sterile alternative for transrectal biopsy in patients with
diabetes mellitus who are at risk of sepsis.
• Position: Dorsal lithotomy
• US probe used using transperineal window. Minimum of
6 cores should be taken three from either side of the
midline.
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Dept of Urology, GRH and KMC, Chennai.
62. Transperineal Prostate Biopsy
Advantages:
• Useful in patients lacking rectum (surgical extirpation,
congenital anomaly).
• Reduced infections and complication rates.
• Improved cancer detection rates,
• Improved anterior and apical sampling,
• Reduced false negative results and
• Reduced risk for underestimating disease volume and
grade.
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Dept of Urology, GRH and KMC, Chennai.
63. Transperineal Prostate Biopsy
Disadvantage:
• Extensive anaesthesia is needed.
• Increased risk of urinary retention with transperineal
biopsy route.
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Dept of Urology, GRH and KMC, Chennai.
64. Transurethral prostate biopsy
• Once advocated for TZ cancers or after negative TRUS
sampling.
• Solitary TZ cancers < 5% of patients.
• Not widely used nowadays with improved in TRUS biopsy
techniques like TRUS/MRI fusion biopsy system.
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Dept of Urology, GRH and KMC, Chennai.
66. Sample Handling
• Biopsy sample is typically placed in 10% formalin .
• No compelling evidence that individual site specific
labeling of cores benefits clinical decision making
regarding the management - Recent AUA white paper
• No more than 2 cores in each jar be packed to avoid
reduction of cancer detection rate through inadequate
tissue sampling.
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Dept of Urology, GRH and KMC, Chennai.
68. • Gleason grades 1 and 2 are no longer recommended for
use, since cancer with those patterns has an outcome no
different from grade 3.
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Dept of Urology, GRH and KMC, Chennai.
69. Gleason’s Scoring
• Ranges from 2 to 10.
• The sum of the two most prevalent Gleason patterns:
primary and secondary patterns
• If only one pattern is present, the primary and secondary
patterns are given the same
• Gleason score be assigned separately for each
anatomically designated site.
• The highest score of tumor will represent the entire case
as the basis to determine treatment
• Any glands showing perineural invasion must be excluded
in assigning Gleason grading as it distorts gland
morphology.
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Dept of Urology, GRH and KMC, Chennai.
71. Report Components
• A prostate biopsy that does not contain glandular tissue
should be reported as diagnostically inadequate.
• Mandatory elements to be reported for a carcinoma-
positive prostate biopsy are:
1. Type of carcinoma;
2. Primary and secondary/worst Gleason grade (per biopsy
site and global);
3. Percentage high-grade carcinoma (global)
4. Extent of carcinoma (in mm or percentage) (at least per
biopsy site)
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Dept of Urology, GRH and KMC, Chennai.
72. Report Components
5. if present: EPE, seminal vesicle invasion, LVI, intraductal
carcinoma/cribriform pattern, peri-neural invasion
6. ISUP grade (global).
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Dept of Urology, GRH and KMC, Chennai.
73. Prolaris Test
• Genetic test done on tissue sample.
• Measure cancer aggressiveness.
• 31 cell cycle associated genes
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Dept of Urology, GRH and KMC, Chennai.
74. Oncotype Dx
• RNA based test.
• Measures cancer aggressiveness.
• 12 carcinoma associated genes
and 5 reference genes
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Dept of Urology, GRH and KMC, Chennai.
76. Color and Power Doppler TRUS
• Based on frequency shift in the reflected sound waves.
• Power Doppler is enhanced Color Doppler and uses
amplitude shift.
• Detects prostate cancer neovascularity.
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Dept of Urology, GRH and KMC, Chennai.
77. Color doppler and Power Doppler
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Dept of Urology, GRH and KMC, Chennai.
78. Color and Power Doppler
• Patients with detectable color Doppler flow within their
dominant tumor at the time of biopsy are at 10 fold
increased risk for PSA recurrence after radical retropubic
prostatectomy.
• Also associated with high gleason grade, increased
incidence of SV invasion and a lower biochemical disease
free survival rate.
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Dept of Urology, GRH and KMC, Chennai.
79. CE TRUS
• Identify microvessels in the range of 10-15 microns.
• Intravenous microbubble is used as the contrast.
• They are constructed with air or higher molecular weight
gas agents encapsulated for longevity in the range 1-10
microns
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Dept of Urology, GRH and KMC, Chennai.
81. Elastography
• Real time sonographic imaging of the prostate at baseline
and under varying degree of compression.
• It adds information about stiffness of prostate tissue.
• Malignant tissue is more stiffer.
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Dept of Urology, GRH and KMC, Chennai.
83. Computerised 3D model-Target Scan
• Uses biplanar images
• Converts the US image into the 3D model.
• Useful for getting sterotactic biopsy
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Dept of Urology, GRH and KMC, Chennai.
85. TRUS/MRI Fusion Biopsy
• Using a software, MRI images are superimposed over the
USG image in real time and the suspicious area in MRI is
targeted using TRUS image.
• It combines the strength of both MRI and TRUS systems.
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Dept of Urology, GRH and KMC, Chennai.
