- Email: [email protected]
Reply to Yaalini Shanmugabavan, Stephanie Guillaumier and Hashim U. Ahmed's Letter to the Editor re: Morgan R. Pokorny, Maarten de Rooij, Earl Duncan, et al. Prospective Study of Diagnostic Accuracy Comparing Prostate Cancer Detection by Transrectal Ultrasound–Guided Biopsy Versus Magnetic Resonance (MR) Imaging with Subsequent MR-guided Biopsy in Men Without Previous Prostate Biopsies. Eur Urol 2014;66:22–9
EUROPEAN UROLOGY 67 (2015) e54–e55
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor Reply to Yaalini Shanmugabavan, Stephanie Guillaumier and Hashim U. Ahmed’s Letter to the Editor re: Morgan R. Pokorny, Maarten de Rooij, Earl Duncan, et al. Prospective Study of Diagnostic Accuracy Comparing Prostate Cancer Detection by Transrectal Ultrasound–Guided Biopsy Versus Magnetic Resonance (MR) Imaging with Subsequent MR-guided Biopsy in Men Without Previous Prostate Biopsies. Eur Urol 2014;66:22–9 When our study was conceived [1], a modality-specific definition was created to allow meaningful comparison of two to four targeted magnetic resonance image (MRI)guided biopsy (MRGB) cores with 12 transrectal ultrasound (TRUS)-guided biopsy (TRUSGB) cores. Shanmugabavan et al. have expressed concern that Gleason 3 + 3 disease of very low volume might not behave as prostate cancer. Only 10 subjects in our MRGB group had intermediate- or high-risk disease on the basis of Gleason 6 disease alone. One patient had two cores of short cancer length (0.5 and 1.5 mm). One subject had two cores of Gleason 6 (2 and 2.8 mm). Two subjects had three and four cores showing significant lengths of Gleason 6. The remaining six subjects had a combined cancer core length in two biopsy cores ranging from 5.2 to 19.5 mm. We submit that if our study was indeed biased, it was biased in favour of TRUSGB for the following reasons: 1. For Gleason 3 + 3 disease, our definition required three out of 12 positive cores (25%) compared to one out of two to four positive cores (25–50%) for MRGB. No patient had more than four MRGB cores taken. Therefore, it is more likely for TRUSGB cores to reach the 25% threshold. 2. The average core length was longer for TRUSGB (15 mm) than for MRGB (13 mm; p < 0.001, two-sample t-test). 3. The urologist performing TRUSGB was blinded to the multiparametric MRI/MRGB protocol, but there was often a blood track visible for recent MRGB. 4. Low-volume Gleason 3 + 3 disease is often invisible on MRI.
the comparison of the MRGB and TRUSGB pathways. The study on which we based the criterion was referenced in our manuscript [1]. The cited TRUS-fusion accuracy of 2 mm is based on the hotspot (ie, most aggressive part) volume distribution of 62 lesions, including many targets of <1 cm in diameter. This is the registration accuracy required to hit 95% of hotspots with just one needle. A 1-cm target would require registration accuracy of 3.1 mm for 95% probability of hitting it with one needle. A system with 5-mm accuracy has probability of hitting a 1-cm target of 61%, 85%, and 94% for one, two, and three needles, respectively. The probability of hitting a 7-mm target with one needle is 31%. Therefore, we considered that current fusion systems might not be accurate enough for correct Gleason grading of smaller targets [2]. Although no head-to-head comparisons have been published, available evidence shows that MRGB resulted in a 41% reduction in TRUSGB undergrading [3] compared to a 32% reduction using MRI/US-fusion-targeted biopsy [4]. Equivocal scans are inevitable for any Likert scale such as Prostate Imaging Reporting and Data System (PIRADS 3). If there are excessive equivocal scans, the inherent usefulness of the test as a risk stratifier is reduced. Higher numbers would reduce the usefulness of the test. The prostate is a dynamic organ. At MRGB, many equivocal ‘‘lesions’’ had changed or disappeared, reflecting ischaemia, inflammation, and atrophy. Our study was performed to the highest possible scientific standards and fulfilled START criteria [5]. We do not accept the assertion of Shanmugabavan et al. that our study methodology falls short of an undisclosed set of ‘‘uniform’’ parameters. References [1] Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound–guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014;66:22–9. [2] van de Ven WJ, Hulsbergen-van de Kaa CA, Hambrock T, Barentsz JO, Huisman HJ. Simulated required accuracy of image
The criterion of <0.7 ml was chosen for tumour significance at radical prostatectomy. This did not influence
registration tools for targeting high-grade cancer components with prostate biopsies. Eur Radiol 2013;23:1401–7.
DOIs of original articles: http://dx.doi.org/10.1016/j.eururo.2014.03.002, http://dx.doi.org/10.1016/j.eururo.2014.08.065. http://dx.doi.org/10.1016/j.eururo.2014.08.066 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY 67 (2015) e54–e55
e55
[3] Hambrock T, Hoeks C, Hulsbergen-van de Kaa C, et al. Prospective
[TD$FIRSNAME]Morgan[TD$FIRSNAME.] [TD$SURNAME]Pokornya,b,*
assessment of prostate cancer aggressiveness using 3-T diffusion-
[TD$FIRSNAME]Wendy[TD$FIRSNAME.] [TD$SURNAME]Van de Venc
weighted magnetic resonance imaging–guided biopsies versus a
[TD$FIRSNAME]Jelle[TD$FIRSNAME.] [TD$SURNAME]Barentszc
systematic 10-core transrectal ultrasound prostate biopsy cohort.
[TD$FIRSNAME]Leslie[TD$FIRSNAME.] [TD$SURNAME]Thompsonb
Eur Urol 2012;61:177–84.
a
[4] Siddiqui MM, Rais-Bahrami S, Truong H, et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. Eur Urol 2013;64:713–9. [5] Moore CM, Kasivisvanathan V, Eggener S, et al. Standards of report-
Urology Department, Onzelievevrouw Ziekenhuis, Aalst, Belgium b
c
Urology Department, The Wesley Hospital, Brisbane, Australia
Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands *Corresponding author. Urology Department, Onzelievevrouw
ing for MRI-targeted biopsy studies (START) of the prostate: recom-
Ziekenhuis, Moorselbaan 164, Aalst 9300, Belgium.
mendations from an International Working Group. Eur Urol 2013;
E-mail address: [email protected] (M. Pokorny).
64:544–52. August 25, 2014
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor Reply to Yaalini Shanmugabavan, Stephanie Guillaumier and Hashim U. Ahmed’s Letter to the Editor re: Morgan R. Pokorny, Maarten de Rooij, Earl Duncan, et al. Prospective Study of Diagnostic Accuracy Comparing Prostate Cancer Detection by Transrectal Ultrasound–Guided Biopsy Versus Magnetic Resonance (MR) Imaging with Subsequent MR-guided Biopsy in Men Without Previous Prostate Biopsies. Eur Urol 2014;66:22–9 When our study was conceived [1], a modality-specific definition was created to allow meaningful comparison of two to four targeted magnetic resonance image (MRI)guided biopsy (MRGB) cores with 12 transrectal ultrasound (TRUS)-guided biopsy (TRUSGB) cores. Shanmugabavan et al. have expressed concern that Gleason 3 + 3 disease of very low volume might not behave as prostate cancer. Only 10 subjects in our MRGB group had intermediate- or high-risk disease on the basis of Gleason 6 disease alone. One patient had two cores of short cancer length (0.5 and 1.5 mm). One subject had two cores of Gleason 6 (2 and 2.8 mm). Two subjects had three and four cores showing significant lengths of Gleason 6. The remaining six subjects had a combined cancer core length in two biopsy cores ranging from 5.2 to 19.5 mm. We submit that if our study was indeed biased, it was biased in favour of TRUSGB for the following reasons: 1. For Gleason 3 + 3 disease, our definition required three out of 12 positive cores (25%) compared to one out of two to four positive cores (25–50%) for MRGB. No patient had more than four MRGB cores taken. Therefore, it is more likely for TRUSGB cores to reach the 25% threshold. 2. The average core length was longer for TRUSGB (15 mm) than for MRGB (13 mm; p < 0.001, two-sample t-test). 3. The urologist performing TRUSGB was blinded to the multiparametric MRI/MRGB protocol, but there was often a blood track visible for recent MRGB. 4. Low-volume Gleason 3 + 3 disease is often invisible on MRI.
the comparison of the MRGB and TRUSGB pathways. The study on which we based the criterion was referenced in our manuscript [1]. The cited TRUS-fusion accuracy of 2 mm is based on the hotspot (ie, most aggressive part) volume distribution of 62 lesions, including many targets of <1 cm in diameter. This is the registration accuracy required to hit 95% of hotspots with just one needle. A 1-cm target would require registration accuracy of 3.1 mm for 95% probability of hitting it with one needle. A system with 5-mm accuracy has probability of hitting a 1-cm target of 61%, 85%, and 94% for one, two, and three needles, respectively. The probability of hitting a 7-mm target with one needle is 31%. Therefore, we considered that current fusion systems might not be accurate enough for correct Gleason grading of smaller targets [2]. Although no head-to-head comparisons have been published, available evidence shows that MRGB resulted in a 41% reduction in TRUSGB undergrading [3] compared to a 32% reduction using MRI/US-fusion-targeted biopsy [4]. Equivocal scans are inevitable for any Likert scale such as Prostate Imaging Reporting and Data System (PIRADS 3). If there are excessive equivocal scans, the inherent usefulness of the test as a risk stratifier is reduced. Higher numbers would reduce the usefulness of the test. The prostate is a dynamic organ. At MRGB, many equivocal ‘‘lesions’’ had changed or disappeared, reflecting ischaemia, inflammation, and atrophy. Our study was performed to the highest possible scientific standards and fulfilled START criteria [5]. We do not accept the assertion of Shanmugabavan et al. that our study methodology falls short of an undisclosed set of ‘‘uniform’’ parameters. References [1] Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound–guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014;66:22–9. [2] van de Ven WJ, Hulsbergen-van de Kaa CA, Hambrock T, Barentsz JO, Huisman HJ. Simulated required accuracy of image
The criterion of <0.7 ml was chosen for tumour significance at radical prostatectomy. This did not influence
registration tools for targeting high-grade cancer components with prostate biopsies. Eur Radiol 2013;23:1401–7.
DOIs of original articles: http://dx.doi.org/10.1016/j.eururo.2014.03.002, http://dx.doi.org/10.1016/j.eururo.2014.08.065. http://dx.doi.org/10.1016/j.eururo.2014.08.066 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY 67 (2015) e54–e55
e55
[3] Hambrock T, Hoeks C, Hulsbergen-van de Kaa C, et al. Prospective
[TD$FIRSNAME]Morgan[TD$FIRSNAME.] [TD$SURNAME]Pokornya,b,*
assessment of prostate cancer aggressiveness using 3-T diffusion-
[TD$FIRSNAME]Wendy[TD$FIRSNAME.] [TD$SURNAME]Van de Venc
weighted magnetic resonance imaging–guided biopsies versus a
[TD$FIRSNAME]Jelle[TD$FIRSNAME.] [TD$SURNAME]Barentszc
systematic 10-core transrectal ultrasound prostate biopsy cohort.
[TD$FIRSNAME]Leslie[TD$FIRSNAME.] [TD$SURNAME]Thompsonb
Eur Urol 2012;61:177–84.
a
[4] Siddiqui MM, Rais-Bahrami S, Truong H, et al. Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy. Eur Urol 2013;64:713–9. [5] Moore CM, Kasivisvanathan V, Eggener S, et al. Standards of report-
Urology Department, Onzelievevrouw Ziekenhuis, Aalst, Belgium b
c
Urology Department, The Wesley Hospital, Brisbane, Australia
Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands *Corresponding author. Urology Department, Onzelievevrouw
ing for MRI-targeted biopsy studies (START) of the prostate: recom-
Ziekenhuis, Moorselbaan 164, Aalst 9300, Belgium.
mendations from an International Working Group. Eur Urol 2013;
E-mail address: [email protected] (M. Pokorny).
64:544–52. August 25, 2014