Saturation Biopsy vs. 3D Spatial Biopsy vs. Free Hand Ultrasound biopsy for Targeted Prostate Cancer Therapies

Transcription

1 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

2

3 Ablation Plan and Cancer Biology Dictates Degree of Precision Necessary John F. Ward and J. Stephen Jones Urology 75(6) June 2010

4 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

5 Precision versus Carpet

6 Saturation Prostate Biopsy PROSTATE MAPPING BIOPSY

7

8 Barzelle 5mm sampling frame 0.5cc tumour 9-12 mm max diameter Rules out 0.5cc lesions with 98% certainty Rules out 0.2cc lesions with 95% certainty 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):

9 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 Scanned and digitized with tumors delineated 3D reconstruction Fixation related shrinkage taken into account Computer TPM simulations conducted Courtesy of Mark Emberton

10 Validity of biopsy max CCL against reference Accuracy values for 0.5 cc lesion detection for increasing cancer core length (CCL) thresholds

11 Validity of biopsy max CCL against reference Accuracy values for 0.2 cc lesion detection for increasing cancer core length (CCL) thresholds

12 Is this really the way to approach Organ preserving prostate ablative therapy?

13 What does this really tell us about targeting? Brawer MK, personal data, 2008.

14

15 How much prostate is really examined with a 100 core prostate needle biopsy of an average (37g) gland?

16

17 3.3% of prostate is removed by 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 ½πr 2 x L cc of tissue per core 100 core saturation biopsy 1.28 cc of tissue Assume a 37.7cc Prostate However.. Pathologist examines a single 5 μm histologic section from each core = cm section Total volume within each core which is examined is cc 100 cores Total volume examined is cc Or % of the prostate volume!

18 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): , 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 slides from an average extirpated prostate 0.17% of entire prostate examined with standard histologic sectioning.

19 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): , 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?

20 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): , 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!!!!

21 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): , 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!!!!!!!!!

22 Saturation Biopsy Conclusion #1 Even 100 cores does not identify all tumors <0.001% of prostate is examined!

23 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?

24 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.

25 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

26 Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens Wise et al. Urology 2002, 60(2) Mean (cm 3 ) IQ Range (cm 3 ) Index tumor volume Total tumor volume Smaller tumor volume Additional foci

27 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

28

29

30 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

31 Saturation Biopsy Conclusion #2 Identifying every prostate tumor may not be necessary to achieve successful cancer treatment, nor is it currently possible.

32 Idealized modeling of the prostate biopsy

33 Saturation Biopsy

34 Moving Target Respiratory movement Swelling Deformation of the capsule

35 Deflection of Bevel Tip Needle

36 Non-idealized world Prostate Tumors are Non- Spherical Prostate tumors are serpiginous Exist in 3-Dimensions

37 Problem #3 with Saturation Biopsy Prostates are not idealized structures

38 What are you really trying to achieve with a saturation biopsy Eliminate the Ray Charles Factor.

39 Work Smarter, Not Harder

40 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

41 Argument FOR Deliberated Biopsy The most efficient number and location of prostate biopsies remains a matter of debate

42 Targeted Prostate Biopsy Using Statistical Image Analysis Yiqiang Zhan, et al. IEEE transactions on medical imaging 26: 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

43 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.

44 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

45 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.

46 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

47 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)

48 Can this type of precision be achieved with a ultrasound guided prostate biopsy?

49 Operator is an independent Predictor of Detecting Prostate Cancer at Transrectal Ultrasound Guided Prostate Biopsy Lawrentschuck, et al. Journal of Urology 2009, 182(12) J Urol 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

50 3D Spatially Oriented Biopsy Removing operator variability Artemis by Eigen

51 3D Spatially Oriented Biopsy Removing operator variability 3D Target Scanning by Envisioneering

52 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

53 Thank you.