- Email: [email protected]
Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift?
EURURO-6246; No. of Pages 3 EUROPEAN UROLOGY XXX (2015) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Gianluca Giannarini a,*, Alberto Briganti b, Alessandro Crestani a, Marta Rossanese a, Francesco Montorsi b, Vincenzo Ficarra a,c a
Urology Unit, Academic Medical Centre Hospital Santa Maria della Misericordia, Udine, Italy;
b
Division of Oncology/Urology Unit, Urological Research
c
Institute, Ospedale San Raffaele, Milan, Italy; Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
Prostate biopsy (PB) is, and is likely to remain, one of the most commonly performed urologic procedures worldwide. Until recently, it has been performed using blinded, systematic, template-based sampling under transrectal ultrasound (TRUS) guidance, with inherent drawbacks of undersampling of significant and oversampling of insignificant prostate cancer (PCa). The introduction of prostate magnetic resonance imaging (MRI) and the increasing use of functional sequences (so-called multiparametric MRI [mpMRI]) and refinements in equipment, protocols, and standardisation of data reporting have revolutionised this practice, and a rationale for image-based targeted sampling has rapidly been built. Data available so far have demonstrated the advantage of mpMRI-targeted PB in detecting a higher proportion of clinically significant cancers using fewer cores compared to conventional sampling [1,2]. Since a substantial change in how PB is performed will have enormous consequences for routine clinical practice and diagnostic/treatment pathways of one the most common malignancies (ie, PCa), it is legitimate to pose the question as to whether the urologic community on a global scale is truly ready to absorb this change. This approach has rapidly attracted interest among practicing urologists, and is now considered a possible new gold standard, especially in the repeat PB setting. However, despite accumulating evidence favouring mpMRI-targeted PB, there are still some open questions and concerns.
1.
Problems with mpMRI
(1) Recent data have shown that mpMRI can detect clinically significant, high-grade tumours with high accuracy when using template mapping PB as the reference standard [3]. However, mpMRI has yet to be formally validated against final pathology of the entire prostate with and without PCa. To the best of our knowledge, only a single diagnostic study on MRI used final pathology of prostate glands with and without cancer as the reference standard, after enrolling patients treated with either radical prostatectomy (RP) or radical cystectomy [4]. A 17% false-positive rate was observed, although the study was not powered to address the issue, with only 18/111 patients having no PCa at final pathology. Moreover, only biparametric MRI was used. (2) Most studies based their analysis on the ‘‘index lesion’’ at mpMRI and the ‘‘index tumour’’ at final pathology of RP specimens. However, the definition of these entities is not uniform across studies, and the concept itself is still prone to criticism because of PCa multifocality and intratumoural heterogeneity. Notably, no single study has ever proved perfect correspondence between the ‘‘index lesion’’ and ‘‘index tumour’’. Moreover, in a recent study, although mpMRI sensitivity was higher for highergrade tumours, 28% of Gleason 7 tumours and 28% of tumours of >1 cm in diameter were missed at final pathology after RP [5].
* Corresponding author. Urology Unit, Academic Medical Centre Hospital Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, IT-33100 Udine, Italy. Tel. +39 0432 552931; Fax: +39 0432 552930. E-mail address: [email protected] (G. Giannarini). http://dx.doi.org/10.1016/j.eururo.2015.05.049 0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049
EURURO-6246; No. of Pages 3 2
EUROPEAN UROLOGY XXX (2015) XXX–XXX
(3) mpMRI may be inaccurate in measuring tumour volume. In an ad hoc study of 84 consecutive patients with final pathology as the reference standard, diffusion-weighted imaging underestimated pathologic volume in 49% of cases by a mean of 0.56 cm3, and multiparametric and target volumes significantly overestimated pathologic volume by a mean of 16% and 44%, with underestimation in 32% and 17% of cases, respectively [6]. This drawback is of utmost importance when, for instance, counselling for focal therapy. (4) Detection of transition zone tumours is a concern. In two small studies, mpMRI did not improve the accuracy of detection and localisation of transition zone cancers compared with T2-weighted imaging alone because of the high rate of false-positive results caused by difficulty in discriminating PCa from nodules of benign hyperplasia [7,8]. (5) The vast majority of publications reporting very high accuracy for mpMRI in detecting PCa and high-grade PCa come from high-volume academic centres of excellence. Virtually no data exist on the learning curve for mpMRI interpretation across different hospital settings. A single study has recently shown that the PCa detection rate for targeted PB significantly increased from 27% to 63% for the first and last groups of patients over a 20-mo time period. Similarly, the negative predictive value of MRI for significant cancer increased from 66.6% to 88.9% [9]. Moreover, only a few studies among the plethora published have specifically evaluated interobserver variability in interpreting mpMRI findings among readers with varying experience in body MRI. (6) mpMRI has high costs and is time-consuming. Formal cost-effectiveness analyses on a large scale and across different health care systems are awaited. 2.
Problems with mpMRI-targeted prostate biopsy
(1) Whether systematic cores should be abandoned when performing MRI-targeted PB remains unknown. Approximately 3–20% of men with either no suspicious lesions on mpMRI or with negative mpMRI-targeted PB harbour clinically significant disease detected via systematic cores [10,11]. We consider this proportion non-negligible from a clinical standpoint. Moreover, no long-term follow-up is available for patients with a negative mpMRI or with cancers detected, as well as missed, by targeted PB alone. (2) The detection rate decreases with increasing prostate volume [12], which is a limitation common to conventional systematic TRUS-guided PB. Knowing the location of MRI-derived targets does not compensate for difficult accessibility to certain areas for sampling (anterior locations in prostates with large adenomas for which the peripheral zone is compressed and laterally displaced), which is a result of the inherent limitations of the biopsy equipment currently available. (3) The number of cores to be taken per lesion and the number of lesions to be sampled remain unknown. It is
(4)
(5)
(6)
(7)
obvious that the greater the number of targeted cores, the weaker is the concept of targeted sampling. Histology parameters available at MRI-targeted PB may not necessarily have the same value as those available at systematic PB. With the former, there is typically an upgrade in Gleason score and a higher percentage of cancer per core compared to the latter [1,2]. Therefore, a new definition of clinically significant disease is urgently required. The decrease in complication rate compared to systematic PB is unproven so far. In particular, the advantage claimed that MRI-informed PB limits infectious morbidity by taking fewer cores awaits verification. From a theoretical standpoint, a single needle puncture in the prostate would be sufficient to cause an infection. Urologists approaching this technique face two learning curves, one related to interpretation of mpMRI findings and the other to the use of software-based MRI-informed fusion-guided sampling. No data are available in this regard. Software-based MRI/TRUS fusion-guided targeted PB is costly and time-consuming, and the cheaper cognitive fusion-guided approach apparently provides an inferior diagnostic yield [1,2].
In conclusion, we believe further scrutiny is warranted before large-scale dissemination of MRI-informed PB takes place. If we had to foresee a major change in PB practice, this would be one in which PB strategy would be personalised according to several determinants (patient age and life expectancy, serum PSA, prostate volume and shape, number of previous biopsies), thus establishing the concept of individualised precision biopsy. Conflicts of interest: The authors have nothing to disclose.
References [1] Valerio M, Donaldson I, Emberton M, et al. Detection of clinically significant prostate cancer using magnetic resonance imaging– ultrasound fusion targeted biopsy: a systematic review. Eur Urol 2015;68:8–19. [2] Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MG. Magnetic resonance imaging–targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2014.11.037 [3] Fu¨tterer JJ, Briganti A, De Visschere P, et al. Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.013 [4] Bains LJ, Studer UE, Froehlich JM, et al. Diffusion-weighted magnetic resonance imaging detects significant prostate cancer with high probability. J Urol 2014;192:737–42. [5] Le JD, Tan N, Shkolyar E, et al. Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology. Eur Urol 2015;67:569–76. [6] Cornud F, Khoury G, Bouazza N, et al. Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation? J Urol 2014;191:1272–9.
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049
EURURO-6246; No. of Pages 3 EUROPEAN UROLOGY XXX (2015) XXX–XXX
3
[7] Delongchamps NB, Rouanne M, Flam T, et al. Multiparametric mag-
[10] Kuru TH, Roethke MC, Seidenader J, et al. Critical evaluation
netic resonance imaging for the detection and localization of prostate
of magnetic resonance imaging targeted, transrectal ultrasound
cancer: combination of T2-weighted, dynamic contrast-enhanced
guided transperineal fusion biopsy for detection of prostate cancer.
and diffusion-weighted imaging. BJU Int 2011;107:1411–8. [8] Hoeks CM, Hambrock T, Yakar D, et al. Transition zone prostate
J Urol 2013;190:1380–6. [11] Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of
cancer: detection and localization with 3-T multiparametric MR
MR/ultrasound fusion-guided biopsy with ultrasound-guided
imaging. Radiology 2013;266:207–17.
biopsy for the diagnosis of prostate cancer. JAMA 2015;313:
[9] Gaziev G, Wadhwa K, Barrett T, et al. Defining the learning curve for
390–7.
multiparametric magnetic resonance imaging (MRI) of the prostate
[12] Walton Diaz A, Hoang AN, Turkbey B, et al. Can magnetic resonance-
using MRI-transrectal ultrasonography (TRUS) fusion-guided trans-
ultrasound fusion biopsy improve cancer detection in enlarged
perineal prostate biopsies as a validation tool. BJU Int. In press.
prostates? J Urol 2013;190:2020–5.
http://dx.doi.org/10.1111/bju.12892
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Gianluca Giannarini a,*, Alberto Briganti b, Alessandro Crestani a, Marta Rossanese a, Francesco Montorsi b, Vincenzo Ficarra a,c a
Urology Unit, Academic Medical Centre Hospital Santa Maria della Misericordia, Udine, Italy;
b
Division of Oncology/Urology Unit, Urological Research
c
Institute, Ospedale San Raffaele, Milan, Italy; Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
Prostate biopsy (PB) is, and is likely to remain, one of the most commonly performed urologic procedures worldwide. Until recently, it has been performed using blinded, systematic, template-based sampling under transrectal ultrasound (TRUS) guidance, with inherent drawbacks of undersampling of significant and oversampling of insignificant prostate cancer (PCa). The introduction of prostate magnetic resonance imaging (MRI) and the increasing use of functional sequences (so-called multiparametric MRI [mpMRI]) and refinements in equipment, protocols, and standardisation of data reporting have revolutionised this practice, and a rationale for image-based targeted sampling has rapidly been built. Data available so far have demonstrated the advantage of mpMRI-targeted PB in detecting a higher proportion of clinically significant cancers using fewer cores compared to conventional sampling [1,2]. Since a substantial change in how PB is performed will have enormous consequences for routine clinical practice and diagnostic/treatment pathways of one the most common malignancies (ie, PCa), it is legitimate to pose the question as to whether the urologic community on a global scale is truly ready to absorb this change. This approach has rapidly attracted interest among practicing urologists, and is now considered a possible new gold standard, especially in the repeat PB setting. However, despite accumulating evidence favouring mpMRI-targeted PB, there are still some open questions and concerns.
1.
Problems with mpMRI
(1) Recent data have shown that mpMRI can detect clinically significant, high-grade tumours with high accuracy when using template mapping PB as the reference standard [3]. However, mpMRI has yet to be formally validated against final pathology of the entire prostate with and without PCa. To the best of our knowledge, only a single diagnostic study on MRI used final pathology of prostate glands with and without cancer as the reference standard, after enrolling patients treated with either radical prostatectomy (RP) or radical cystectomy [4]. A 17% false-positive rate was observed, although the study was not powered to address the issue, with only 18/111 patients having no PCa at final pathology. Moreover, only biparametric MRI was used. (2) Most studies based their analysis on the ‘‘index lesion’’ at mpMRI and the ‘‘index tumour’’ at final pathology of RP specimens. However, the definition of these entities is not uniform across studies, and the concept itself is still prone to criticism because of PCa multifocality and intratumoural heterogeneity. Notably, no single study has ever proved perfect correspondence between the ‘‘index lesion’’ and ‘‘index tumour’’. Moreover, in a recent study, although mpMRI sensitivity was higher for highergrade tumours, 28% of Gleason 7 tumours and 28% of tumours of >1 cm in diameter were missed at final pathology after RP [5].
* Corresponding author. Urology Unit, Academic Medical Centre Hospital Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, IT-33100 Udine, Italy. Tel. +39 0432 552931; Fax: +39 0432 552930. E-mail address: [email protected] (G. Giannarini). http://dx.doi.org/10.1016/j.eururo.2015.05.049 0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049
EURURO-6246; No. of Pages 3 2
EUROPEAN UROLOGY XXX (2015) XXX–XXX
(3) mpMRI may be inaccurate in measuring tumour volume. In an ad hoc study of 84 consecutive patients with final pathology as the reference standard, diffusion-weighted imaging underestimated pathologic volume in 49% of cases by a mean of 0.56 cm3, and multiparametric and target volumes significantly overestimated pathologic volume by a mean of 16% and 44%, with underestimation in 32% and 17% of cases, respectively [6]. This drawback is of utmost importance when, for instance, counselling for focal therapy. (4) Detection of transition zone tumours is a concern. In two small studies, mpMRI did not improve the accuracy of detection and localisation of transition zone cancers compared with T2-weighted imaging alone because of the high rate of false-positive results caused by difficulty in discriminating PCa from nodules of benign hyperplasia [7,8]. (5) The vast majority of publications reporting very high accuracy for mpMRI in detecting PCa and high-grade PCa come from high-volume academic centres of excellence. Virtually no data exist on the learning curve for mpMRI interpretation across different hospital settings. A single study has recently shown that the PCa detection rate for targeted PB significantly increased from 27% to 63% for the first and last groups of patients over a 20-mo time period. Similarly, the negative predictive value of MRI for significant cancer increased from 66.6% to 88.9% [9]. Moreover, only a few studies among the plethora published have specifically evaluated interobserver variability in interpreting mpMRI findings among readers with varying experience in body MRI. (6) mpMRI has high costs and is time-consuming. Formal cost-effectiveness analyses on a large scale and across different health care systems are awaited. 2.
Problems with mpMRI-targeted prostate biopsy
(1) Whether systematic cores should be abandoned when performing MRI-targeted PB remains unknown. Approximately 3–20% of men with either no suspicious lesions on mpMRI or with negative mpMRI-targeted PB harbour clinically significant disease detected via systematic cores [10,11]. We consider this proportion non-negligible from a clinical standpoint. Moreover, no long-term follow-up is available for patients with a negative mpMRI or with cancers detected, as well as missed, by targeted PB alone. (2) The detection rate decreases with increasing prostate volume [12], which is a limitation common to conventional systematic TRUS-guided PB. Knowing the location of MRI-derived targets does not compensate for difficult accessibility to certain areas for sampling (anterior locations in prostates with large adenomas for which the peripheral zone is compressed and laterally displaced), which is a result of the inherent limitations of the biopsy equipment currently available. (3) The number of cores to be taken per lesion and the number of lesions to be sampled remain unknown. It is
(4)
(5)
(6)
(7)
obvious that the greater the number of targeted cores, the weaker is the concept of targeted sampling. Histology parameters available at MRI-targeted PB may not necessarily have the same value as those available at systematic PB. With the former, there is typically an upgrade in Gleason score and a higher percentage of cancer per core compared to the latter [1,2]. Therefore, a new definition of clinically significant disease is urgently required. The decrease in complication rate compared to systematic PB is unproven so far. In particular, the advantage claimed that MRI-informed PB limits infectious morbidity by taking fewer cores awaits verification. From a theoretical standpoint, a single needle puncture in the prostate would be sufficient to cause an infection. Urologists approaching this technique face two learning curves, one related to interpretation of mpMRI findings and the other to the use of software-based MRI-informed fusion-guided sampling. No data are available in this regard. Software-based MRI/TRUS fusion-guided targeted PB is costly and time-consuming, and the cheaper cognitive fusion-guided approach apparently provides an inferior diagnostic yield [1,2].
In conclusion, we believe further scrutiny is warranted before large-scale dissemination of MRI-informed PB takes place. If we had to foresee a major change in PB practice, this would be one in which PB strategy would be personalised according to several determinants (patient age and life expectancy, serum PSA, prostate volume and shape, number of previous biopsies), thus establishing the concept of individualised precision biopsy. Conflicts of interest: The authors have nothing to disclose.
References [1] Valerio M, Donaldson I, Emberton M, et al. Detection of clinically significant prostate cancer using magnetic resonance imaging– ultrasound fusion targeted biopsy: a systematic review. Eur Urol 2015;68:8–19. [2] Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MG. Magnetic resonance imaging–targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2014.11.037 [3] Fu¨tterer JJ, Briganti A, De Visschere P, et al. Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.013 [4] Bains LJ, Studer UE, Froehlich JM, et al. Diffusion-weighted magnetic resonance imaging detects significant prostate cancer with high probability. J Urol 2014;192:737–42. [5] Le JD, Tan N, Shkolyar E, et al. Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology. Eur Urol 2015;67:569–76. [6] Cornud F, Khoury G, Bouazza N, et al. Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation? J Urol 2014;191:1272–9.
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049
EURURO-6246; No. of Pages 3 EUROPEAN UROLOGY XXX (2015) XXX–XXX
3
[7] Delongchamps NB, Rouanne M, Flam T, et al. Multiparametric mag-
[10] Kuru TH, Roethke MC, Seidenader J, et al. Critical evaluation
netic resonance imaging for the detection and localization of prostate
of magnetic resonance imaging targeted, transrectal ultrasound
cancer: combination of T2-weighted, dynamic contrast-enhanced
guided transperineal fusion biopsy for detection of prostate cancer.
and diffusion-weighted imaging. BJU Int 2011;107:1411–8. [8] Hoeks CM, Hambrock T, Yakar D, et al. Transition zone prostate
J Urol 2013;190:1380–6. [11] Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of
cancer: detection and localization with 3-T multiparametric MR
MR/ultrasound fusion-guided biopsy with ultrasound-guided
imaging. Radiology 2013;266:207–17.
biopsy for the diagnosis of prostate cancer. JAMA 2015;313:
[9] Gaziev G, Wadhwa K, Barrett T, et al. Defining the learning curve for
390–7.
multiparametric magnetic resonance imaging (MRI) of the prostate
[12] Walton Diaz A, Hoang AN, Turkbey B, et al. Can magnetic resonance-
using MRI-transrectal ultrasonography (TRUS) fusion-guided trans-
ultrasound fusion biopsy improve cancer detection in enlarged
perineal prostate biopsies as a validation tool. BJU Int. In press.
prostates? J Urol 2013;190:2020–5.
http://dx.doi.org/10.1111/bju.12892
Please cite this article in press as: Giannarini G, et al. Dismiss Systematic Transrectal Ultrasound-guided and Embrace Targeted Magnetic Resonance Imaging–informed Prostate Biopsy: Is the Paradigm Ready to Shift? Eur Urol (2015), http://dx.doi.org/ 10.1016/j.eururo.2015.05.049