Download Transrectal 12-Core Biopsy is superior to Saturation biopsy for

Saturation Biopsy vs. 3D Spatial
Biopsy vs. Free Hand Ultrasound
biopsy for Targeted Prostate Cancer
Therapies
John F. Ward, MD
Assistant Professor
University of Texas M. D. Anderson Cancer Center
Ablation Plan and Cancer Biology
Dictates Degree of Precision
Necessary
John F. Ward and J. Stephen Jones
Urology 75(6) 1258-60. June 2010
Improving Biopsy Technique to
Answer the Question “Where” not
“if”
Ultrasound guided Random Biopsy
• Prostate Mapping Biopsy (Saturation
biopsy)
• 3D Image rendering with Spatial Biopsy
• Free Hand Ultrasound Guided Biopsy
Precision versus
Carpet
Saturation Prostate Biopsy
PROSTATE MAPPING BIOPSY
Barzelle 5mm sampling frame
0.5cc tumour
Rules out 0.5cc lesions with 98% certainty
Rules out 0.2cc lesions with 95% certainty
9-12 mm max diameter
0.2cc tumour
5-6 mm max diameter
Bott SR et al. Extensive transperineal template biopsies of prostate:
modified technique and results. Urology 2006;68(5):1037-41.
Can Maximum Cancer Core Length Involvement on Template Transperineal
Prostate Mapping Biopsies Rule-in and Rule-out Clinically Significant
Prostate Cancer?
•
•
Methods:
126 RP step-section
specimens 1999 – 2001
•
Scanned and digitized with
tumors delineated
•
•
3D reconstruction
Fixation related shrinkage
taken into account
•
Computer TPM simulations
conducted
Courtesy of Mark Emberton
Validity of biopsy max CCL against reference
Accuracy values for ≥ 0.5 cc lesion detection for increasing
cancer core length (CCL) thresholds
Validity of biopsy max CCL against reference
Accuracy values for ≥ 0.2 cc lesion detection for
increasing cancer core length (CCL) thresholds
Is this really the way to
approach Organ
preserving prostate
ablative therapy?
¿What does this really tell us about targeting?
Brawer MK, personal data, 2008.
How much prostate is
really examined with a
100 core prostate needle
biopsy of an average
(37g) gland?
How Much prostate is actually examined by a biopsy core?
•Biopsy core can be modeled
as a semi-cylindrical volume
•Each semi-cylindrical biopsy
core from a standard needle
has the length 12.7 mm and the
radius 0.8 mm.
•Provides a volume of
•
½πr2 x L
•
0.0128 cc of tissue per
core
•
100 core saturation
biopsy
•
1.28 cc of tissue
•Assume a 37.7cc Prostate
•3.3% of prostate is removed by
However…..
•Pathologist examines a single 5‐μm histologic section from each core = 0.0005 cm section
•Total volume within each core which is examined is 0.0000005 cc
•100 cores
•Total volume examined is 0.00005cc
•Or 0.000132% of the prostate volume!
Complete Histologic Serial Sectioning of a
Prostate Gland with Adenocarcinoma
Peter A. Humphrey, M.D., Ph.D.
The American Journal of Surgical Pathology 17(5): 468-472, 1993
• Current Pathology Techniques are Partial
Samplings
• Single 5-μm histologic section from a 3-mm
tissue block results
• Results in a pathologist examining
approximately 12-24 slides from an average
extirpated prostate
• 0.17% of entire prostate examined with
standard histologic sectioning.
Complete Histologic Serial Sectioning of a
Prostate Gland with Adenocarcinoma
Peter A. Humphrey, M.D., Ph.D.
The American Journal of Surgical Pathology 17(5): 468-472, 1993
• Undertook this study to determine IF a complete
sectioning of the prostate provided different
important information
• Is important information lost in the
unexamined tissue.
• What don’t we know?
Complete Histologic Serial Sectioning of a
Prostate Gland with Adenocarcinoma
Peter A. Humphrey, M.D., Ph.D.
The American Journal of Surgical Pathology 17(5): 468-472, 1993
• 37.7-g prostate sectioned at 3mm intervals
• 19-slides representing 0.2% of the entire
prostate
• Complete sectioning of the remaining 99.8% of
the prostate at 5-μm intervals
• 2,678 Sections!!!!
Complete Histologic Serial Sectioning of a
Prostate Gland with Adenocarcinoma
Peter A. Humphrey, M.D., Ph.D.
The American Journal of Surgical Pathology 17(5): 468-472, 1993
• Overall Gleason Score did not
change from that assigned with
initial 19 slides.
• Percentage carcinoma value of
17.9% for initial set of 19 slides
very close to percentage
carcinoma value of 16.4%
calculated from 2,678 slides.
• Ultimate Saturation Biopsy!!!!!!!!!
Saturation Biopsy
Conclusion #1
•
Even 100 cores does not identify all
tumors
•
<0.001% of prostate is examined!
Does every tumor in the
prostate need to be
identified and treated in
order to successfully apply
organ preserving therapy in
an oncologically efficient
manner?
Dominant Prostate Tumor Drives
Clinical Biology
While the natural history of different prostate
cancer foci remains unknown, evidence exists
that the index tumor is the biologic driving force
behind the malignant potential of prostate
cancer.
Morphologic and clinical significance of multifocal prostate
cancers in radical prostatectomy specimens
Wise et al.
Urology 2002, 60(2)
• examine the histologic details of small, independent
cancers compared with the largest (index) tumor and
their impact on PSA failure in 486 men treated only by
prostatectomy
Morphologic and clinical significance of multifocal prostate
cancers in radical prostatectomy specimens
Wise et al.
Urology 2002, 60(2)
Mean (cm3)
IQ Range (cm3)
Index tumor volume
4.16
1.37‐5.11
Total tumor volume
4.78
1.73‐6.28
Smaller tumor volume
0.63
0.01‐0.85
Additional foci
2.92
1‐4
Morphologic and clinical significance of multifocal prostate
cancers in radical prostatectomy specimens
Wise et al.
Urology 2002, 60(2)
• Smaller cancers are not a significant predictor of PSA
failure after radical prostatectomy
• The index cancer volume is equally predictive of PSA
failure after radical prostatectomy as total cancer
volume (index plus smaller cancers)
• Suggestion that the largest carcinoma may increase
its volume by assimilation of adjacent independent
tumors
Index Tumor Conclusions
• Many patients with multifocal disease have
small volume secondary tumors of lower
grade that are unlikely to affect clinical
biology
• Pathologic landscape suggests that
targeting index tumor can alter clinical
course
Saturation Biopsy
Conclusion #2
•
Identifying every prostate tumor may not
be necessary to achieve successful
cancer treatment, nor is it currently
possible.
Idealized modeling of
the prostate biopsy
Saturation Biopsy
Moving Target
•
Respiratory movement
•
Swelling
•
Deformation of the capsule
Deflection of Bevel Tip
Needle
Non-idealized world
•
Prostate Tumors are NonSpherical
•
Prostate tumors are
serpiginous
•
Exist in 3-Dimensions
Problem #3 with
Saturation Biopsy
•
Prostates are not idealized structures
What are you really trying to achieve
with a saturation biopsy
•
Eliminate the “Ray Charles”
Factor.
Work Smarter, Not
Harder
Some day…….
Prostate cancer imaging
• Ultrasound
• Contrast Enhanced Ultrasound
• Histoscanning
• Elastography
• T2 Weighted MRI
• MR spectroscopy
• Dynamic contrast-enhanced
MRI
• Diffusion weight MRI
• B-mode Ultrasound
• Power Doppler Ultrasound
Argument FOR Deliberated
Biopsy
The most efficient number and location
of prostate biopsies remains a matter of
debate
Targeted Prostate Biopsy Using Statistical Image Analysis
Yiqiang Zhan, et al.
IEEE transactions on medical imaging 26:2007
•158 whole mount prostatectomy
specimens from CPDR/AFIP
•Prostate cancer has higher incidence
in peripheral zones. The mid and the
apical zones exhibit higher cancer
incidence than the base zones
•all of which are in agreement with what is
known from clinical studies
•Determined the position parameters
of each biopsy cut-out so that the
probability that no cancerous tissue is
included in the semi-cylinders is
minimized
Targeted Prostate Biopsy Using Statistical Image Analysis
Yiqiang Zhan, et al.
IEEE transactions on medical imaging 26:2007
Warping of the Atlas to
Patient Images
(a)‐(c) Optimal positioning of six needles
(d) Cross‐validated performance assuming exact and approximate (within a neighborhood of diameter 4 mm) needle placement.
Targeted Prostate Biopsy Using Statistical Image Analysis
Yiqiang Zhan, et al.
IEEE transactions on medical imaging 26:2007
CONCLUSIONS
• the optimized biopsy strategy generated in the
atlas space is mapped to a specific patient space
using an automated segmentation and elastic
registration method.
• can achieve 94%–96% detection accuracy,
• much higher than the detection rate (70.5%)
obtained on the same datasets via the
commonly biopsy strategy
Biopsy Schemes with the Fewest Cores for Detecting 95%
of the Prostate Cancers Detected by a 24-Core Biopsy
Scattoni, et al.
Eur Urol 2010, 57(1)
• Prospective study
• 617 men undergoing first PBx for cause.
• 24 PBx overlapping of medial sextant, lateral sextant, octant subcapsular, and quadrant transition cores. • determined the best combination of sampling sites that detected >95% of the cancers with the minimum number of biopsy cores.
Biopsy Schemes with the Fewest Cores for Detecting 95%
of the Prostate Cancers Detected by a 24-Core Biopsy
Scattoni, et al.
Eur Urol 2010, 57(1)
The most advantageous set of the biopsy core that maximizes the cancer‐detection rate with the minimum number of cores in patients with:
(A)negative digital rectal examination, prostate volume (PV) =60 cm3, and age =65 yr; (B)negative DRE, PV =60 cm3, and age >65 yr; (C)Negative DRE and PV >60 cm3;
(D)a positive DRE
Biopsy Schemes with the Fewest Cores for Detecting 95%
of the Prostate Cancers Detected by a 24-Core Biopsy
Scattoni, et al.
Eur Urol 2010, 57(1)
Can this type of precision
be achieved with a
ultrasound guided prostate
biopsy?
Operator is an independent Predictor of Detecting Prostate Cancer at Transrectal Ultrasound Guided Prostate Biopsy
Lawrentschuck, et al.
Journal of Urology 2009, 182(12)
•
4,629 men undergoing first biopsy
•
4 different experienced providers
•
Multivariate analysis of all covariates
•
operator remained a significant multivariate predictor
of cancer detection (OR 0.67 to 0.89, p 0.003)
•
E.g.: a biopsy by operator 3 was 0.67 times as likely to
detect positive cancer on TRUS-BX as the referent
operator
J Urol 2009, 182(12).
3D Spatially Oriented Biopsy
Removing operator variability
Artemis by Eigen
3D Spatially Oriented Biopsy
Removing operator variability
3D Target Scanning by Envisioneering
Conclusions
•
•
•
Saturation Biopsy does not provide the
information nor the precision for which it
is credited
Free hand biopsy is subject to too much
variability
Spatially oriented Biopsy provides a
smarter tool for prostate biopsy
Thank you.