- Email: [email protected]
The Role of Ipsilateral and Contralateral Transrectal Ultrasound-guided Systematic Prostate Biopsy in Men With Unilateral Magnetic Resonance Imaging Lesion Undergoing Magnetic Resonance Imaging-ultrasound Fusion-targeted Prostate Biopsy
Accepted Manuscript Title: The Role of Ipsilateral and Contralateral TRUS-Guided Systematic Prostate Biopsy in Men with Unilateral MRI Lesion Undergoing MRI-US Fusion-Targeted Prostate Biopsy Author: Darren J. Bryk, Elton Llukani, Samir S. Taneja, Andrew B. Rosenkrantz, William C. Huang, Herbert Lepor PII: DOI: Reference:
S0090-4295(16)30837-8 http://dx.doi.org/doi: 10.1016/j.urology.2016.11.017 URL 20137
To appear in:
Urology
Received date: Accepted date:
24-8-2016 11-11-2016
Please cite this article as: Darren J. Bryk, Elton Llukani, Samir S. Taneja, Andrew B. Rosenkrantz, William C. Huang, Herbert Lepor, The Role of Ipsilateral and Contralateral TRUSGuided Systematic Prostate Biopsy in Men with Unilateral MRI Lesion Undergoing MRI-US Fusion-Targeted Prostate Biopsy, Urology (2016), http://dx.doi.org/doi: 10.1016/j.urology.2016.11.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title PAGE: The Role of Ipsilateral and Contralateral TRUS-Guided Systematic Prostate Biopsy in Men with Unilateral MRI Lesion Undergoing MRI-US Fusion-Targeted Prostate Biopsy
Darren J. Bryk, M.D. 1; Elton Llukani, M.D. 1; Samir S. Taneja, M.D. 1; Andrew B. Rosenkrantz, M.D. 1, 2; William C. Huang, M.D. 1; Herbert Lepor, M.D. 1 1 Department
of Urology, New York University Langone Medical Center, New York, USA
2 Department
of Radiology, New York University Langone Medical Center, New York, USA
Corresponding Author:
Herbert Lepor, M.D. Professor and Martin Spatz Chairman Department of Urology NYU School of Medicine 150 East 32nd Street – 2nd Floor New York, NY 10016 Tel.: +1 646 825-6380 Fax: +1 646 825-6399 Email: [email protected]
1
Page 1 of 17
Manuscript Word Count (without title page, abstract, references, tables): 2,138 Abstract Word Count: 201 Tables: 2 Figures: 0 References: 29
Keywords: Prostatic cancer; Magnetic resonance imaging; Biopsy; Diagnostic imaging; Ultrasonography
2
Page 2 of 17
ABSTRACT Objective To determine how ipsilateral (ipsi) and contralateral (contra) systematic biopsies (SB) impacts detection of clinically significant versus insignificant prostate cancer (PCa) in men with unilateral MRI lesion undergoing MRI fusion target biopsy (MRF-TB). Materials and Methods 211 cases with one unilateral MRI lesion were subjected to SB and MRF-TB. Biopsy tissue cores from the MRF-TB, ipsi-SB and contra-SB were analyzed separately. Results A direct relationship was observed between MRI suspicious score (SS) and detection of any cancer, Gleason 6 PCa and Gleason > 6 PCa. MRF-TB alone, MRF-TB + ipsi-SB and MRF-TB + contra-SB detected 64.1%, 89.1% and 76.1% of all PCa, respectively, 53.5%, 81.4% and 69.8% of Gleason 6 PCa, respectively, and 73.5%, 96.0% and 81.6% of Gleason >6 PCa, respectively. MRF-TB + ipsi-SB detected 96% of clinically significant PCa and avoided detection of 18.6% of clinically insignificant PCa. MRF-TB + contra-SB detected 81.6% of clinically significant PCa and avoided detection of 30.2% of clinically insignificant PCa. Conclusion Our study suggests that ipsi-SB should be added to MRF-TB as detection of clinically significant PCa increases with only a modest increase in clinically insignificant PCa
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detection. Contra-SB in this setting may be deferred since it primarily detects clinically insignificant PCa. INTRODUCTION Systematic prostate biopsy (SB) is typically performed by random systematic tissue sampling of the peripheral zone under trans-rectal ultrasound guidance. The primary limitations of SB are its high detection rate of clinically insignificant disease which has implications related to cost, morbidity of unnecessary treatment, and anxiety associated with active surveillance. Another limitation of SB is under-detection of clinically significant disease.(1, 2)
Increasing evidence shows that the addition of magnetic resonance imaging ultrasound fusion-targeted prostate biopsy (MRF-TB) to SB increases the cancer detection rate (CDR) of clinically significant disease.(2-9) However, the combination of MRF-TB and SB also exacerbates over-detection of clinically insignificant disease. Ideally, prostate biopsy strategies must find a balance between detection of clinically significant versus clinically insignificant disease. The present study independently evaluated the SB obtained ipsilateral (ipsi-SB) and contralateral (contra-SB) to a unilateral MRI lesion subjected to MRF-TB in order to determine the relative contribution of these biopsy sites to detection of clinically significant versus clinically insignificant disease. The hypothesis being tested was that contra- SB disproportionately increases the detection of insignificant prostate cancer and therefore should not be routinely performed. This hypothesis is based on the very high negative predictive value of mpMRI for clinically significant prostate cancer.(10-12) Cases 4
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with a unilateral MRI lesion were selected since this would be the ideal cohort to question the utility of contra-SB. MATERIALS AND METHODS Beginning in June 2012, only uro-oncologists perform prostate biopsy at our institution. The overwhelming majority (>95%) of candidates for prostate biopsy presenting to our institution since 2012 underwent pre-biopsy mpMRI on a 3-T clinical instrument using a previously described technique.(3, 13, 14) The axial T2 weighted-images, dynamic contrast enhancement images, and diffusion weighted images (acquired b-values of 50 and 1000 seconds per mm2; calculated b-value of 1,500 seconds per mm2; reconstructed apparent diffusion coefficient map) were reviewed and, using a 5-point suspicion scale, the MRI lesions were assigned a suspicion score (ss) of 2 (clinically significant disease is unlikely to be present), 3 (clinically significant disease is equivocal), 4 (clinically significant disease is likely to be present) or 5 (clinically significant disease is highly likely to be present).(15, 16) All men assigned a suspicious score on pre-biopsy mpMRI underwent an MRF-TB. MRF-TB was performed using an Artemis prostate biopsy system and ProFuse (Eigen, Grass Valley, CA, USA) software for MRI segmentation, co-registration of MRI and US images, and three dimensional biopsy planning as previously described.(3, 13, 14) A single uro-radiologist performed or directly supervised the MRI segmentation. Prostate ultrasound was performed using the Pro Focus (BK Medical, Peabody, MA, USA) or Noblus ultrasound systems (Hitachi Aloka Medical America, Wallingford, CT, USA). After targeting 4 biopsies into each MRI lesion, SB was performed by sampling 12 software-populated spatially distributed sites selected by the Artemis device.
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Data and Statistical Analysis A total of 211 consecutive cases with a single unilateral MRI lesion subjected to both MRFTB and SB were identified from 679 biopsy cases performed by two experienced users of the Profuse and Artemis systems (HL or WCH). None of the cases had biopsy proven cancer. Demographics, serum PSA levels at time of mpMRI, mpMRI interpretations, and prostate biopsy pathology reports were reviewed. The linear lengths of the individual biopsy cores and the linear lengths of all Gleason pattern disease were recorded. The percentages of Gleason patterns in the individual biopsy cores were calculated. Clinically significant and clinically insignificant disease were defined as Gleason >6 PCa and Gleason 6, respectively. The MRF-TB, ipsi-SB, and contra-SB were analyzed separately. The sensitivities for detection of any cancer, clinically significant cancer and clinically significant cancer were determined for various combinations of MRF-TB, ipsi-SB and contra-SB. Inter-group differences between sensitivities were considered statistically significant if the mean of one group did not overlap with the 95% confidence interval of another group.
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RESULTS A total of 211 consecutive men with an elevated PSA and/or prostate nodule and a single unilateral MRI lesion on mpMRI underwent MRF-TB and SB. Table 1 shows characteristics of the study population, as well as the relationship between ss of the MRI lesions and CDR. Fifty-nine cancers were detected by MRF-TB. Both overall CDRs and the detection rates of Gleason >6 PCa increased with increasing ss. As shown in Table 2, a strategy to perform only MRF-TB + ipsi-SB would detect 96% of clinically significant PCa and avoid detection of 18.6% of clinically insignificant PCa. The ratio of additional clinically significant PCa versus additional clinically insignificant PCa detected by adding ipsi-SB to MRF-TB was 0.92:1. Additionally, as shown in Table 2, a strategy to perform only MRF-TB + contra-SB would detect 81.6% of clinically significant PCa and avoid detection of 30.2% of clinically insignificant PCa. The ratio of additional clinically significant PCa to additional clinically insignificant PCa detected by adding contraSB to MRF-TB is 0.57:1. The two cases of Gleason >6 disease identified exclusively by contra-SB had linear volumes of Gleason pattern 4 of 0.2mm and 1.2mm.
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DISCUSSION The widespread acceptance of PSA screening, SB, and aggressive treatment of PCa beginning in the 1990’s are major factors contributing to the profound decline in prostate cancer mortality rates.(17, 18) This widely accepted paradigm for screening, detection and treatment of prostate cancer has substantial limitations. Due to the low specificity of PSA screening, approximately 70% of men undergoing prostate biopsies are exposed to the morbidity of unnecessary biopsies.(19) Approximately half of cancers detected by SB are Gleason 6 PCa.(20) According to National Cancer Center Network guidelines, many Gleason 6 PCa should be managed with AS in order to limit over-treatment of the disease.(21) A limitation of AS strategies is that about half of the prostate glands with Gleason 6 PCa detected by SB harbor unrecognized aggressive disease.(22) The challenge for the urology community is to develop clinical pathways that preferentially detect clinically significant disease.
There is compelling and consistent evidence that adding MRF-TB to SB increases both the detection of clinically significant (Gleason >6 PCa) and clinically insignificant (Gleason 6 PCa) disease.(2, 3, 5, 6, 14, 23, 24) Therefore, the study was not designed to compare cancer detection rates for MRF-TB vs SB. Rather, the objective was to elucidate a biopsy strategy that would optimize the detection of clinically significant vs insignificant disease
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for those practitioners who are performing MRF-TB. Since the negative predictive value of mpMRI for clinically significant cancer exceeds 90% (10-12), we speculated that contra-SB in men with a unifocal MRI lesion may simply add to the detection of clinically insignificant cancers whereas ipsi-SB may increase detection of clinically significant cancers by additional sampling of the MRI target since a component of the computer generated ipsi-SB often overlies the MRI target. To our knowledge, the present study is the first to independently assess the contribution of ipsi-SB and contra-SB to detection of any cancer, Gleason 6 PCa, and Gleason >6 PCa.
Our overall CDR was 43.6%, which is in relative agreement with other recently reported contemporary series combining MRF-TB and SB.(3, 6, 25) Our institutional criteria for assigning a ss to an MRI lesion identified on mpMRI has been previously reported.(15) The CDR in the present study for ss 2, 3, 4, and 5 were 7.8%, 19.2%, 51.1% and 100%, respectively. In our institutional series, which was not limited to unilateral MRI lesions, the CDRs for ss 2, 3, 4, and 5 were 15.4%, 22.9%, 42.1%, and 85.7%, respectively.(13)
The goal for prostate biopsy strategies should be to maximize detection of clinically significant disease and minimize detection of clinically insignificant disease. In the present study, we followed the consensus of previously reported contemporary biopsy series which differentiated clinically significant disease and clinically insignificant disease based on presence or absence of Gleason pattern 4.(14, 26) Epstein et al validated grading the aggressiveness of PCa detected in biopsy and surgical specimens on a scale between 1 to 4 9
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based primarily on the presence and extent of Gleason pattern 4. A subsequent consensus of leading genito-urinary pathologists recommended adoption of this grading system.(27) While the presence of any Gleason pattern 4 was associated with higher rates of biochemical recurrences, we recognize that true clinical significance must ultimately consider age, co-morbidities, and extent of disease.
Based on the observed superiority of MRF-TB to preferentially detect clinically significant disease, it has become the cornerstone of our prostate biopsy protocol. The objective of the present study was to elucidate the value of adding ipsi-SB and/or contra-SB to MRF-TB as we attempt to optimize our biopsy regimen. One limitation of MRF-TB was that it failed to detect 13 (26.5%) of the 49 Gleason >6 PCa. The addition of ipsi-SB to MRF-TB identified 12 additional cases of Gleason 6 PCa and 11 cases of Gleason >6 PCa. The addition of ipsiSB to MRF-TB detected 96% of the clinically significant PCa. The comparable increase in both clinically significant and clinically insignificant PCa by adding ipsi-SB in our judgment is a reasonable trade off. By eliminating contra-SB, only 4.1% of clinically significant disease would have gone undetected, while 18.6% of the clinically insignificant disease would be undetected.
The two cases of Gleason >6 disease identified exclusively by contra-SB had linear volumes of Gleason pattern 4 of 0.2mm and 1.2mm which is below the threshold for detection by mpMRI. One may argue that this very low volume of Gleason pattern 4 may not represent clinically significant disease in various clinical scenarios. We explored how a 10
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recommendation to eliminate contra-SB might impact treatment decisions. If one assumes that Gleason >6 PCa is the factor driving decision to perform radical prostatectomy, then failure to perform a contra-SB would have influenced the management of only 2 (0.9%) of 211 cases, thereby decreasing the overall rate of radical prostatectomy from 23.2% to 22.3%. If one assumes that presence of bilateral Gleason >6 PCa in our cohort would disqualify men with a single MRI lesion from focal ablation, then failure to perform a contra-SB would have resulted in 4 (1.9%) of the 211 cases undergoing inappropriate focal ablation and the overall rate of proper focal ablation would have decreased from 23.2% to 21.3%.
Overall, 11 cases of Gleason >6 PCa were detected by the ipsi-SB and missed by MRF-TB. The most likely explanation is mis-registration, which has been demonstrated using simulations or phantoms;(28) MRI-US fusion technology is in its early stages of development and has yet to be optimized. Another explanation is that at our institution, the SB is performed with the MRI lesion(s) visualized. At the time of SB, we consistently directed the corresponding ipsi-SB into the MRI lesion if they overlapped, thereby providing additional sampling of the MRI lesion. The optimal number of targeted biopsies remains undefined. It is possible directing the SB into the target may have increased detection of significant cancers simply due to increased sampling. It has also been shown that mpMRI often under-estimates the extent of disease.(29) It is also conceivable that the ipsi-SB is sampling components of the tumor not visible on mpMRI. Another possibility is
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that multi-focal clinically significant disease may not be a random event and may occur preferentially on the side of the index tumor, which is sampled by the ipsi-SB.
There are limitations of our study that merit discussion. The cohort, by design, was limited to cases with a single MRI lesion. In addition, we did not stratify the analysis between men with and without prior history of prostate biopsy. In addition, while all included patients had only a single reported MRI lesion, it is possible that a fraction of these lesions extended into the contralateral lobe, though without this extension being noted in the radiology report. We did not utilize the PI-RADS scoring system to assess the risk of detecting prostate cancer since it was not developed at the time we initiated the study. We have shown a strong correlation between our suspicious scoring system and PI-RADS (16). We biopsied all MRI lesions independent of ss. Recommendations for ipsilateral and contralateral SB may be dependent on the ss of the MRI lesion. Our limited sample size did not allow stratification of our results according to ss of the MRI lesions. The finding of a negative biopsy does not indicate the lack of prostate cancer. Finally, the urologists and radiologists interpreting the mpMRI and performing the MRF-TB are highly experienced with the technology. Therefore, the outcomes may not be generalizable to centers with less experience.
CONCLUCION
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The current study is relevant to those practitioners who have adopted MRF-TB and are questioning the role of simultaneous SB. Our study suggests that ipsi-SB should be performed at the time of MRF-TB as it increases the detection rate of clinically significant PCa with only a modest increase in detection of clinically insignificant PCa. Deferral of contra-SB associated with a normal mpMRI should be considered since it rarely increases the detection of clinically significant disease while significantly increasing detection of clinically insignificant disease.
References 1. King CR, McNeal JE, Gill H, Presti JC, Jr. Extended prostate biopsy scheme improves reliability of Gleason grading: implications for radiotherapy patients. Int J Radiat Oncol Biol Phys. 2004;59(2):386-91. 2. Siddiqui MM, Rais-Bahrami S, Turkbey B, George AK, Rothwax J, Shakir N, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama. 2015;313(4):390-7. 3. Mendhiratta N, Rosenkrantz AB, Meng X, Wysock JS, Fenstermaker M, Huang R, et al. Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification. The Journal of urology. 2015;194(6):1601-6. 4. Sonn GA, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, et al. Value of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigen. European urology. 2014;65(4):809-15. 5. Pinto PA, Chung PH, Rastinehad AR, Baccala AA, Jr., Kruecker J, Benjamin CJ, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. The Journal of urology. 2011;186(4):1281-5. 6. Siddiqui MM, Rais-Bahrami S, Truong H, Stamatakis L, Vourganti S, Nix J, et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. European urology. 2013;64(5):713-9. 7. Bjurlin MA, Meng X, Le Nobin J, Wysock JS, Lepor H, Rosenkrantz AB, et al. Optimization of Prostate Biopsy: the Role of Magnetic Resonance Imaging Targeted Biopsy in Detection, Localization and Risk Assessment. The Journal of urology. 2014;192(3):648-58. 8. Pokorny MR, de Rooij M, Duncan E, Schroder FH, Parkinson R, Barentsz JO, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal
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ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MRguided biopsy in men without previous prostate biopsies. European urology. 2014;66(1):22-9. 9. Rais-Bahrami S, Siddiqui MM, Turkbey B, Stamatakis L, Logan J, Hoang AN, et al. Utility of multiparametric magnetic resonance imaging suspicion levels for detecting prostate cancer. The Journal of urology. 2013;190(5):1721-7. 10. Villers A, Puech P, Mouton D, Leroy X, Ballereau C, Lemaitre L. Dynamic contrast enhanced, pelvic phased array magnetic resonance imaging of localized prostate cancer for predicting tumor volume: correlation with radical prostatectomy findings. J Urol. 2006;176(6 Pt 1):2432-7. 11. Numao N, Yoshida S, Komai Y, Ishii C, Kagawa M, Kijima T, et al. Usefulness of prebiopsy multiparametric magnetic resonance imaging and clinical variables to reduce initial prostate biopsy in men with suspected clinically localized prostate cancer. J Urol. 2013;190(2):502-8. 12. Arumainayagam N, Ahmed HU, Moore CM, Freeman A, Allen C, Sohaib SA, et al. Multiparametric MR imaging for detection of clinically significant prostate cancer: a validation cohort study with transperineal template prostate mapping as the reference standard. Radiology. 2013;268(3):761-9. 13. Wysock JS, Rosenkrantz AB, Huang WC, Stifelman MD, Lepor H, Deng FM, et al. A prospective, blinded comparison of magnetic resonance (MR) imaging-ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial. European urology. 2014;66(2):343-51. 14. Meng X, Rosenkrantz AB, Mendhiratta N, Fenstermaker M, Huang R, Wysock JS, et al. Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion-targeted Prostate Biopsy Outcomes. European urology. 2016;69(3):512-7. 15. Rosenkrantz AB, Kim S, Lim RP, Hindman N, Deng FM, Babb JS, et al. Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert scales. Radiology. 2013;269(2):482-92. 16. Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. European radiology. 2012;22(4):746-57. 17. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7-30. 18. Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, et al. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer causes & control : CCC. 2008;19(2):175-81. 19. Welch HG, Fisher ES, Gottlieb DJ, Barry MJ. Detection of prostate cancer via biopsy in the Medicare-SEER population during the PSA era. Journal of the National Cancer Institute. 2007;99(18):1395-400. 20. Cooperberg MR, Broering JM, Kantoff PW, Carroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. The Journal of urology. 2007;178(3 Pt 2):S149. 21. Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D'Amico AV, et al. Prostate cancer, version 2.2014. J Natl Compr Canc Netw. 2014;12(5):686-718. 22. Mufarrij P, Sankin A, Godoy G, Lepor H. Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy. Urology. 2010;76(3):689-92. 23. Mendhiratta N, Meng X, Rosenkrantz AB, Wysock JS, Fenstermaker M, Huang R, et al. Prebiopsy MRI and MRI-ultrasound Fusion-targeted Prostate Biopsy in Men With Previous Negative Biopsies: Impact on Repeat Biopsy Strategies. Urology. 2015;86(6):1192-9. 24. Rastinehad AR, Abboud SF, George AK, Frye TP, Ho R, Chelluri R, et al. Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-
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Institutional External Validation by a Propensity Score Matched Cohort. The Journal of urology. 2016; 195(6):1737-43. 25. Sonn GA, Natarajan S, Margolis DJ, MacAiran M, Lieu P, Huang J, et al. Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device. The Journal of urology. 2013;189(1):86-91. 26. Oberlin DT, Casalino DD, Miller FH, Matuelwicz RS, Perry KT, Nadler RB, et al. Diagnostic Value of Guided Biopsies: Fusion and Cognitive-RegistrationMagnetic Resonance Imaging Versus Conventional Ultrasound Biopsy of the Prostate. Urology. 2016;92:75-9. 27. Epstein JI. A new contemporary prostate cancer grading system. Pathology international. 2015;DOI:10.1111/pin.12353. 28. Martin PR, Cool DW, Romagnoli C, Fenster A, Ward AD. Magnetic resonance imagingtargeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis. Med Phys. 2014;41(7):073504. 29. Le Nobin J, Orczyk C, Deng FM, Melamed J, Rusinek H, Taneja SS, et al. Prostate tumour volumes: evaluation of the agreement between magnetic resonance imaging and histology using novel co-registration software. BJU international. 2014;114(6b):E105-12.
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Table 1- Baseline Characteristics (n=211) Median Age (IQR) Median PSA Prior to MRI (IQR) Positive DRE (n, %) Prior Prostate Biopsy (n, %)
mpMRI ss (n) 2 (77) 3 (73) 4 (45) 5 (16) Total (211) IQR= Interquartile Range
61.0 (56-66) 5.3 (3.8-6.9) 44 (20.9) 87 (41.2)
Any Cancer (n, %) 6 (7.8) 14 (19.2) 23 (51.1) 16 (100) 59 (28.0)
MRF-TB Gleason 6 (n, %) 4 (5.2) 6 (8.2) 11 (24.4) 2 (12.5) 23 (10.9)
Gleason >6 (n, %) 2 (2.6) 8 (11.0) 12 (26.7) 14 (87.5) 36 (17.1)
DRE= Digital rectal exam ss= suspicion score MRF-TB= MRI-US fusion targeted biopsy mpMRI ss= multiparametric Magnetic Resonance Imaging suspicion score
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Table 2- Cancer Detection Rate and Sensitivity For MRF-TB Combined with ISB, CSB or SB Any cancer
Gleason score 6
Gleason score >6
n (%)
Sensitivity (95% CI)
n (%)
Sensitivity (95% CI)
n (%)
Sensitivity (95% CI)
59 (28.0)
0.641 (0.534-0.737)
23 (10.9)
0.535 (0.378-0.685)
36 (17.1)
0.735 (0.587-0.846)
(MRF-TB) + ISB
82 (38.9)
0.891 (0.805-0.944)
35 (16.6)
0.814 (0.661-0.911)
47 (22.3)
0.96 (0.849-0.993)
(MRF-TB) + CSB
70 (33.2)
0.761 (0.659-0.841)
30 (14.2)
0.698 (0.537-0.823)
40 (19.0)
0.816 (0.675-0.908)
(MRF-TB) + SB
92 (43.6)
1.0 (0.95-1.0)
43 (20.4)
1.0 (0.898-1.0)
49 (23.2)
1.0 (0.909-1.0)
Site(s) of Biopsy MRF-TB
CI= Confidence Interval MRF-TB= MRI-US fusion targeted biopsy Ipsi-SB= Ipsilateral (to the CSR) (random) systematic biopsy Contra-SB= Contralateral (to the CSR) (random) systematic biopsy SB= Systematic biopsy
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S0090-4295(16)30837-8 http://dx.doi.org/doi: 10.1016/j.urology.2016.11.017 URL 20137
To appear in:
Urology
Received date: Accepted date:
24-8-2016 11-11-2016
Please cite this article as: Darren J. Bryk, Elton Llukani, Samir S. Taneja, Andrew B. Rosenkrantz, William C. Huang, Herbert Lepor, The Role of Ipsilateral and Contralateral TRUSGuided Systematic Prostate Biopsy in Men with Unilateral MRI Lesion Undergoing MRI-US Fusion-Targeted Prostate Biopsy, Urology (2016), http://dx.doi.org/doi: 10.1016/j.urology.2016.11.017. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title PAGE: The Role of Ipsilateral and Contralateral TRUS-Guided Systematic Prostate Biopsy in Men with Unilateral MRI Lesion Undergoing MRI-US Fusion-Targeted Prostate Biopsy
Darren J. Bryk, M.D. 1; Elton Llukani, M.D. 1; Samir S. Taneja, M.D. 1; Andrew B. Rosenkrantz, M.D. 1, 2; William C. Huang, M.D. 1; Herbert Lepor, M.D. 1 1 Department
of Urology, New York University Langone Medical Center, New York, USA
2 Department
of Radiology, New York University Langone Medical Center, New York, USA
Corresponding Author:
Herbert Lepor, M.D. Professor and Martin Spatz Chairman Department of Urology NYU School of Medicine 150 East 32nd Street – 2nd Floor New York, NY 10016 Tel.: +1 646 825-6380 Fax: +1 646 825-6399 Email: [email protected]
1
Page 1 of 17
Manuscript Word Count (without title page, abstract, references, tables): 2,138 Abstract Word Count: 201 Tables: 2 Figures: 0 References: 29
Keywords: Prostatic cancer; Magnetic resonance imaging; Biopsy; Diagnostic imaging; Ultrasonography
2
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ABSTRACT Objective To determine how ipsilateral (ipsi) and contralateral (contra) systematic biopsies (SB) impacts detection of clinically significant versus insignificant prostate cancer (PCa) in men with unilateral MRI lesion undergoing MRI fusion target biopsy (MRF-TB). Materials and Methods 211 cases with one unilateral MRI lesion were subjected to SB and MRF-TB. Biopsy tissue cores from the MRF-TB, ipsi-SB and contra-SB were analyzed separately. Results A direct relationship was observed between MRI suspicious score (SS) and detection of any cancer, Gleason 6 PCa and Gleason > 6 PCa. MRF-TB alone, MRF-TB + ipsi-SB and MRF-TB + contra-SB detected 64.1%, 89.1% and 76.1% of all PCa, respectively, 53.5%, 81.4% and 69.8% of Gleason 6 PCa, respectively, and 73.5%, 96.0% and 81.6% of Gleason >6 PCa, respectively. MRF-TB + ipsi-SB detected 96% of clinically significant PCa and avoided detection of 18.6% of clinically insignificant PCa. MRF-TB + contra-SB detected 81.6% of clinically significant PCa and avoided detection of 30.2% of clinically insignificant PCa. Conclusion Our study suggests that ipsi-SB should be added to MRF-TB as detection of clinically significant PCa increases with only a modest increase in clinically insignificant PCa
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detection. Contra-SB in this setting may be deferred since it primarily detects clinically insignificant PCa. INTRODUCTION Systematic prostate biopsy (SB) is typically performed by random systematic tissue sampling of the peripheral zone under trans-rectal ultrasound guidance. The primary limitations of SB are its high detection rate of clinically insignificant disease which has implications related to cost, morbidity of unnecessary treatment, and anxiety associated with active surveillance. Another limitation of SB is under-detection of clinically significant disease.(1, 2)
Increasing evidence shows that the addition of magnetic resonance imaging ultrasound fusion-targeted prostate biopsy (MRF-TB) to SB increases the cancer detection rate (CDR) of clinically significant disease.(2-9) However, the combination of MRF-TB and SB also exacerbates over-detection of clinically insignificant disease. Ideally, prostate biopsy strategies must find a balance between detection of clinically significant versus clinically insignificant disease. The present study independently evaluated the SB obtained ipsilateral (ipsi-SB) and contralateral (contra-SB) to a unilateral MRI lesion subjected to MRF-TB in order to determine the relative contribution of these biopsy sites to detection of clinically significant versus clinically insignificant disease. The hypothesis being tested was that contra- SB disproportionately increases the detection of insignificant prostate cancer and therefore should not be routinely performed. This hypothesis is based on the very high negative predictive value of mpMRI for clinically significant prostate cancer.(10-12) Cases 4
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with a unilateral MRI lesion were selected since this would be the ideal cohort to question the utility of contra-SB. MATERIALS AND METHODS Beginning in June 2012, only uro-oncologists perform prostate biopsy at our institution. The overwhelming majority (>95%) of candidates for prostate biopsy presenting to our institution since 2012 underwent pre-biopsy mpMRI on a 3-T clinical instrument using a previously described technique.(3, 13, 14) The axial T2 weighted-images, dynamic contrast enhancement images, and diffusion weighted images (acquired b-values of 50 and 1000 seconds per mm2; calculated b-value of 1,500 seconds per mm2; reconstructed apparent diffusion coefficient map) were reviewed and, using a 5-point suspicion scale, the MRI lesions were assigned a suspicion score (ss) of 2 (clinically significant disease is unlikely to be present), 3 (clinically significant disease is equivocal), 4 (clinically significant disease is likely to be present) or 5 (clinically significant disease is highly likely to be present).(15, 16) All men assigned a suspicious score on pre-biopsy mpMRI underwent an MRF-TB. MRF-TB was performed using an Artemis prostate biopsy system and ProFuse (Eigen, Grass Valley, CA, USA) software for MRI segmentation, co-registration of MRI and US images, and three dimensional biopsy planning as previously described.(3, 13, 14) A single uro-radiologist performed or directly supervised the MRI segmentation. Prostate ultrasound was performed using the Pro Focus (BK Medical, Peabody, MA, USA) or Noblus ultrasound systems (Hitachi Aloka Medical America, Wallingford, CT, USA). After targeting 4 biopsies into each MRI lesion, SB was performed by sampling 12 software-populated spatially distributed sites selected by the Artemis device.
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Data and Statistical Analysis A total of 211 consecutive cases with a single unilateral MRI lesion subjected to both MRFTB and SB were identified from 679 biopsy cases performed by two experienced users of the Profuse and Artemis systems (HL or WCH). None of the cases had biopsy proven cancer. Demographics, serum PSA levels at time of mpMRI, mpMRI interpretations, and prostate biopsy pathology reports were reviewed. The linear lengths of the individual biopsy cores and the linear lengths of all Gleason pattern disease were recorded. The percentages of Gleason patterns in the individual biopsy cores were calculated. Clinically significant and clinically insignificant disease were defined as Gleason >6 PCa and Gleason 6, respectively. The MRF-TB, ipsi-SB, and contra-SB were analyzed separately. The sensitivities for detection of any cancer, clinically significant cancer and clinically significant cancer were determined for various combinations of MRF-TB, ipsi-SB and contra-SB. Inter-group differences between sensitivities were considered statistically significant if the mean of one group did not overlap with the 95% confidence interval of another group.
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RESULTS A total of 211 consecutive men with an elevated PSA and/or prostate nodule and a single unilateral MRI lesion on mpMRI underwent MRF-TB and SB. Table 1 shows characteristics of the study population, as well as the relationship between ss of the MRI lesions and CDR. Fifty-nine cancers were detected by MRF-TB. Both overall CDRs and the detection rates of Gleason >6 PCa increased with increasing ss. As shown in Table 2, a strategy to perform only MRF-TB + ipsi-SB would detect 96% of clinically significant PCa and avoid detection of 18.6% of clinically insignificant PCa. The ratio of additional clinically significant PCa versus additional clinically insignificant PCa detected by adding ipsi-SB to MRF-TB was 0.92:1. Additionally, as shown in Table 2, a strategy to perform only MRF-TB + contra-SB would detect 81.6% of clinically significant PCa and avoid detection of 30.2% of clinically insignificant PCa. The ratio of additional clinically significant PCa to additional clinically insignificant PCa detected by adding contraSB to MRF-TB is 0.57:1. The two cases of Gleason >6 disease identified exclusively by contra-SB had linear volumes of Gleason pattern 4 of 0.2mm and 1.2mm.
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DISCUSSION The widespread acceptance of PSA screening, SB, and aggressive treatment of PCa beginning in the 1990’s are major factors contributing to the profound decline in prostate cancer mortality rates.(17, 18) This widely accepted paradigm for screening, detection and treatment of prostate cancer has substantial limitations. Due to the low specificity of PSA screening, approximately 70% of men undergoing prostate biopsies are exposed to the morbidity of unnecessary biopsies.(19) Approximately half of cancers detected by SB are Gleason 6 PCa.(20) According to National Cancer Center Network guidelines, many Gleason 6 PCa should be managed with AS in order to limit over-treatment of the disease.(21) A limitation of AS strategies is that about half of the prostate glands with Gleason 6 PCa detected by SB harbor unrecognized aggressive disease.(22) The challenge for the urology community is to develop clinical pathways that preferentially detect clinically significant disease.
There is compelling and consistent evidence that adding MRF-TB to SB increases both the detection of clinically significant (Gleason >6 PCa) and clinically insignificant (Gleason 6 PCa) disease.(2, 3, 5, 6, 14, 23, 24) Therefore, the study was not designed to compare cancer detection rates for MRF-TB vs SB. Rather, the objective was to elucidate a biopsy strategy that would optimize the detection of clinically significant vs insignificant disease
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for those practitioners who are performing MRF-TB. Since the negative predictive value of mpMRI for clinically significant cancer exceeds 90% (10-12), we speculated that contra-SB in men with a unifocal MRI lesion may simply add to the detection of clinically insignificant cancers whereas ipsi-SB may increase detection of clinically significant cancers by additional sampling of the MRI target since a component of the computer generated ipsi-SB often overlies the MRI target. To our knowledge, the present study is the first to independently assess the contribution of ipsi-SB and contra-SB to detection of any cancer, Gleason 6 PCa, and Gleason >6 PCa.
Our overall CDR was 43.6%, which is in relative agreement with other recently reported contemporary series combining MRF-TB and SB.(3, 6, 25) Our institutional criteria for assigning a ss to an MRI lesion identified on mpMRI has been previously reported.(15) The CDR in the present study for ss 2, 3, 4, and 5 were 7.8%, 19.2%, 51.1% and 100%, respectively. In our institutional series, which was not limited to unilateral MRI lesions, the CDRs for ss 2, 3, 4, and 5 were 15.4%, 22.9%, 42.1%, and 85.7%, respectively.(13)
The goal for prostate biopsy strategies should be to maximize detection of clinically significant disease and minimize detection of clinically insignificant disease. In the present study, we followed the consensus of previously reported contemporary biopsy series which differentiated clinically significant disease and clinically insignificant disease based on presence or absence of Gleason pattern 4.(14, 26) Epstein et al validated grading the aggressiveness of PCa detected in biopsy and surgical specimens on a scale between 1 to 4 9
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based primarily on the presence and extent of Gleason pattern 4. A subsequent consensus of leading genito-urinary pathologists recommended adoption of this grading system.(27) While the presence of any Gleason pattern 4 was associated with higher rates of biochemical recurrences, we recognize that true clinical significance must ultimately consider age, co-morbidities, and extent of disease.
Based on the observed superiority of MRF-TB to preferentially detect clinically significant disease, it has become the cornerstone of our prostate biopsy protocol. The objective of the present study was to elucidate the value of adding ipsi-SB and/or contra-SB to MRF-TB as we attempt to optimize our biopsy regimen. One limitation of MRF-TB was that it failed to detect 13 (26.5%) of the 49 Gleason >6 PCa. The addition of ipsi-SB to MRF-TB identified 12 additional cases of Gleason 6 PCa and 11 cases of Gleason >6 PCa. The addition of ipsiSB to MRF-TB detected 96% of the clinically significant PCa. The comparable increase in both clinically significant and clinically insignificant PCa by adding ipsi-SB in our judgment is a reasonable trade off. By eliminating contra-SB, only 4.1% of clinically significant disease would have gone undetected, while 18.6% of the clinically insignificant disease would be undetected.
The two cases of Gleason >6 disease identified exclusively by contra-SB had linear volumes of Gleason pattern 4 of 0.2mm and 1.2mm which is below the threshold for detection by mpMRI. One may argue that this very low volume of Gleason pattern 4 may not represent clinically significant disease in various clinical scenarios. We explored how a 10
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recommendation to eliminate contra-SB might impact treatment decisions. If one assumes that Gleason >6 PCa is the factor driving decision to perform radical prostatectomy, then failure to perform a contra-SB would have influenced the management of only 2 (0.9%) of 211 cases, thereby decreasing the overall rate of radical prostatectomy from 23.2% to 22.3%. If one assumes that presence of bilateral Gleason >6 PCa in our cohort would disqualify men with a single MRI lesion from focal ablation, then failure to perform a contra-SB would have resulted in 4 (1.9%) of the 211 cases undergoing inappropriate focal ablation and the overall rate of proper focal ablation would have decreased from 23.2% to 21.3%.
Overall, 11 cases of Gleason >6 PCa were detected by the ipsi-SB and missed by MRF-TB. The most likely explanation is mis-registration, which has been demonstrated using simulations or phantoms;(28) MRI-US fusion technology is in its early stages of development and has yet to be optimized. Another explanation is that at our institution, the SB is performed with the MRI lesion(s) visualized. At the time of SB, we consistently directed the corresponding ipsi-SB into the MRI lesion if they overlapped, thereby providing additional sampling of the MRI lesion. The optimal number of targeted biopsies remains undefined. It is possible directing the SB into the target may have increased detection of significant cancers simply due to increased sampling. It has also been shown that mpMRI often under-estimates the extent of disease.(29) It is also conceivable that the ipsi-SB is sampling components of the tumor not visible on mpMRI. Another possibility is
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that multi-focal clinically significant disease may not be a random event and may occur preferentially on the side of the index tumor, which is sampled by the ipsi-SB.
There are limitations of our study that merit discussion. The cohort, by design, was limited to cases with a single MRI lesion. In addition, we did not stratify the analysis between men with and without prior history of prostate biopsy. In addition, while all included patients had only a single reported MRI lesion, it is possible that a fraction of these lesions extended into the contralateral lobe, though without this extension being noted in the radiology report. We did not utilize the PI-RADS scoring system to assess the risk of detecting prostate cancer since it was not developed at the time we initiated the study. We have shown a strong correlation between our suspicious scoring system and PI-RADS (16). We biopsied all MRI lesions independent of ss. Recommendations for ipsilateral and contralateral SB may be dependent on the ss of the MRI lesion. Our limited sample size did not allow stratification of our results according to ss of the MRI lesions. The finding of a negative biopsy does not indicate the lack of prostate cancer. Finally, the urologists and radiologists interpreting the mpMRI and performing the MRF-TB are highly experienced with the technology. Therefore, the outcomes may not be generalizable to centers with less experience.
CONCLUCION
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The current study is relevant to those practitioners who have adopted MRF-TB and are questioning the role of simultaneous SB. Our study suggests that ipsi-SB should be performed at the time of MRF-TB as it increases the detection rate of clinically significant PCa with only a modest increase in detection of clinically insignificant PCa. Deferral of contra-SB associated with a normal mpMRI should be considered since it rarely increases the detection of clinically significant disease while significantly increasing detection of clinically insignificant disease.
References 1. King CR, McNeal JE, Gill H, Presti JC, Jr. Extended prostate biopsy scheme improves reliability of Gleason grading: implications for radiotherapy patients. Int J Radiat Oncol Biol Phys. 2004;59(2):386-91. 2. Siddiqui MM, Rais-Bahrami S, Turkbey B, George AK, Rothwax J, Shakir N, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama. 2015;313(4):390-7. 3. Mendhiratta N, Rosenkrantz AB, Meng X, Wysock JS, Fenstermaker M, Huang R, et al. Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification. The Journal of urology. 2015;194(6):1601-6. 4. Sonn GA, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, et al. Value of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigen. European urology. 2014;65(4):809-15. 5. Pinto PA, Chung PH, Rastinehad AR, Baccala AA, Jr., Kruecker J, Benjamin CJ, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. The Journal of urology. 2011;186(4):1281-5. 6. Siddiqui MM, Rais-Bahrami S, Truong H, Stamatakis L, Vourganti S, Nix J, et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. European urology. 2013;64(5):713-9. 7. Bjurlin MA, Meng X, Le Nobin J, Wysock JS, Lepor H, Rosenkrantz AB, et al. Optimization of Prostate Biopsy: the Role of Magnetic Resonance Imaging Targeted Biopsy in Detection, Localization and Risk Assessment. The Journal of urology. 2014;192(3):648-58. 8. Pokorny MR, de Rooij M, Duncan E, Schroder FH, Parkinson R, Barentsz JO, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal
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ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MRguided biopsy in men without previous prostate biopsies. European urology. 2014;66(1):22-9. 9. Rais-Bahrami S, Siddiqui MM, Turkbey B, Stamatakis L, Logan J, Hoang AN, et al. Utility of multiparametric magnetic resonance imaging suspicion levels for detecting prostate cancer. The Journal of urology. 2013;190(5):1721-7. 10. Villers A, Puech P, Mouton D, Leroy X, Ballereau C, Lemaitre L. Dynamic contrast enhanced, pelvic phased array magnetic resonance imaging of localized prostate cancer for predicting tumor volume: correlation with radical prostatectomy findings. J Urol. 2006;176(6 Pt 1):2432-7. 11. Numao N, Yoshida S, Komai Y, Ishii C, Kagawa M, Kijima T, et al. Usefulness of prebiopsy multiparametric magnetic resonance imaging and clinical variables to reduce initial prostate biopsy in men with suspected clinically localized prostate cancer. J Urol. 2013;190(2):502-8. 12. Arumainayagam N, Ahmed HU, Moore CM, Freeman A, Allen C, Sohaib SA, et al. Multiparametric MR imaging for detection of clinically significant prostate cancer: a validation cohort study with transperineal template prostate mapping as the reference standard. Radiology. 2013;268(3):761-9. 13. Wysock JS, Rosenkrantz AB, Huang WC, Stifelman MD, Lepor H, Deng FM, et al. A prospective, blinded comparison of magnetic resonance (MR) imaging-ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial. European urology. 2014;66(2):343-51. 14. Meng X, Rosenkrantz AB, Mendhiratta N, Fenstermaker M, Huang R, Wysock JS, et al. Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion-targeted Prostate Biopsy Outcomes. European urology. 2016;69(3):512-7. 15. Rosenkrantz AB, Kim S, Lim RP, Hindman N, Deng FM, Babb JS, et al. Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert scales. Radiology. 2013;269(2):482-92. 16. Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. European radiology. 2012;22(4):746-57. 17. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7-30. 18. Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, et al. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer causes & control : CCC. 2008;19(2):175-81. 19. Welch HG, Fisher ES, Gottlieb DJ, Barry MJ. Detection of prostate cancer via biopsy in the Medicare-SEER population during the PSA era. Journal of the National Cancer Institute. 2007;99(18):1395-400. 20. Cooperberg MR, Broering JM, Kantoff PW, Carroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. The Journal of urology. 2007;178(3 Pt 2):S149. 21. Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D'Amico AV, et al. Prostate cancer, version 2.2014. J Natl Compr Canc Netw. 2014;12(5):686-718. 22. Mufarrij P, Sankin A, Godoy G, Lepor H. Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy. Urology. 2010;76(3):689-92. 23. Mendhiratta N, Meng X, Rosenkrantz AB, Wysock JS, Fenstermaker M, Huang R, et al. Prebiopsy MRI and MRI-ultrasound Fusion-targeted Prostate Biopsy in Men With Previous Negative Biopsies: Impact on Repeat Biopsy Strategies. Urology. 2015;86(6):1192-9. 24. Rastinehad AR, Abboud SF, George AK, Frye TP, Ho R, Chelluri R, et al. Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-
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Institutional External Validation by a Propensity Score Matched Cohort. The Journal of urology. 2016; 195(6):1737-43. 25. Sonn GA, Natarajan S, Margolis DJ, MacAiran M, Lieu P, Huang J, et al. Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device. The Journal of urology. 2013;189(1):86-91. 26. Oberlin DT, Casalino DD, Miller FH, Matuelwicz RS, Perry KT, Nadler RB, et al. Diagnostic Value of Guided Biopsies: Fusion and Cognitive-RegistrationMagnetic Resonance Imaging Versus Conventional Ultrasound Biopsy of the Prostate. Urology. 2016;92:75-9. 27. Epstein JI. A new contemporary prostate cancer grading system. Pathology international. 2015;DOI:10.1111/pin.12353. 28. Martin PR, Cool DW, Romagnoli C, Fenster A, Ward AD. Magnetic resonance imagingtargeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis. Med Phys. 2014;41(7):073504. 29. Le Nobin J, Orczyk C, Deng FM, Melamed J, Rusinek H, Taneja SS, et al. Prostate tumour volumes: evaluation of the agreement between magnetic resonance imaging and histology using novel co-registration software. BJU international. 2014;114(6b):E105-12.
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Table 1- Baseline Characteristics (n=211) Median Age (IQR) Median PSA Prior to MRI (IQR) Positive DRE (n, %) Prior Prostate Biopsy (n, %)
mpMRI ss (n) 2 (77) 3 (73) 4 (45) 5 (16) Total (211) IQR= Interquartile Range
61.0 (56-66) 5.3 (3.8-6.9) 44 (20.9) 87 (41.2)
Any Cancer (n, %) 6 (7.8) 14 (19.2) 23 (51.1) 16 (100) 59 (28.0)
MRF-TB Gleason 6 (n, %) 4 (5.2) 6 (8.2) 11 (24.4) 2 (12.5) 23 (10.9)
Gleason >6 (n, %) 2 (2.6) 8 (11.0) 12 (26.7) 14 (87.5) 36 (17.1)
DRE= Digital rectal exam ss= suspicion score MRF-TB= MRI-US fusion targeted biopsy mpMRI ss= multiparametric Magnetic Resonance Imaging suspicion score
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Table 2- Cancer Detection Rate and Sensitivity For MRF-TB Combined with ISB, CSB or SB Any cancer
Gleason score 6
Gleason score >6
n (%)
Sensitivity (95% CI)
n (%)
Sensitivity (95% CI)
n (%)
Sensitivity (95% CI)
59 (28.0)
0.641 (0.534-0.737)
23 (10.9)
0.535 (0.378-0.685)
36 (17.1)
0.735 (0.587-0.846)
(MRF-TB) + ISB
82 (38.9)
0.891 (0.805-0.944)
35 (16.6)
0.814 (0.661-0.911)
47 (22.3)
0.96 (0.849-0.993)
(MRF-TB) + CSB
70 (33.2)
0.761 (0.659-0.841)
30 (14.2)
0.698 (0.537-0.823)
40 (19.0)
0.816 (0.675-0.908)
(MRF-TB) + SB
92 (43.6)
1.0 (0.95-1.0)
43 (20.4)
1.0 (0.898-1.0)
49 (23.2)
1.0 (0.909-1.0)
Site(s) of Biopsy MRF-TB
CI= Confidence Interval MRF-TB= MRI-US fusion targeted biopsy Ipsi-SB= Ipsilateral (to the CSR) (random) systematic biopsy Contra-SB= Contralateral (to the CSR) (random) systematic biopsy SB= Systematic biopsy
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