- Email: [email protected]
Is Targeted Biopsy Applicable to Patients on Active Surveillance?
EURURO-6854; No. of Pages 2 EUROPEAN UROLOGY XXX (2016) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority Referring to the article published on pp. x–y of this issue
Is Targeted Biopsy Applicable to Patients on Active Surveillance? Kris Prado a, Robert E. Reiter a,b,* a
Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; b Institute of Urologic Oncology,
Los Angeles, CA, USA
Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) hold the promise of added precision in our approach to staging and classification of prostate cancer. In this issue of European Urology, Ma and colleagues [1] examine the utility of this diagnostic modality in the active surveillance (AS) population. They demonstrate that among patients enrolled in AS at their institution, addition of TB to systematic biopsy (SB) does not add significant benefit in terms of reclassifying patients on confirmatory biopsy or detecting higher-grade disease while on AS. Rather, SB resulted in identification of higher-grade disease more often than TB in the AS cohort: TB led to the diagnosis of Gleason score (GS) 7 in 7/103 patients (6.8%), while SB diagnosed GS 7 in 21/103 patients (20.4%). When combined, TB and SB diagnosed GS 7 in 25/103 patients (24.2%). Despite the lack of benefit in detecting highergrade disease in patients on AS, the authors did identify a number of patients with GS 7 disease detected by combining TB and SB as opposed to SB alone in patients undergoing confirmatory biopsy or presenting for initial biopsy (statistically significant): 3/54 patients (5.5%) in the confirmatory biopsy group and 12/73 patients in the diagnostic biopsy group (16.4%). This study contrasts with investigations in our institution and others [2–4] supporting the utility of mpMRI and TB in the AS population. Hu and colleagues [5] demonstrated that the presence of Prostate Imaging-Reporting and Data System (PIRADS) 4 and 5 lesions in AS patients undergoing confirmatory biopsy resulted in a high rate of reclassification (47% and 100%, respectively) beyond the Epstein criteria. In addition, Filson and colleagues [6] demonstrated that the presence of a PIRADS 3 lesion was a poor predictor of clinically significant prostate cancer, and
reiterated the strong association between PIRADS 4/5 lesions and clinically significant prostate cancer in the confirmatory biopsy setting. The study by Ma et al shows only a modest association between PIRADS 4/5 lesions and clinically significant prostate cancer in the confirmatory biopsy setting, and no association in the AS setting. Several factors can explain this discrepancy. First, the patient population studied by Ma et al is smaller and based on stricter eligibility criteria for AS (very low-risk prostate cancer) compared to our institution. The incidence of PIRADS 3 lesions among the confirmatory biopsy group (48%) and the AS group (58%) was higher than what we have observed for patients being considered for AS (41%) [6]. Since these lesions correlate poorly with clinically significant prostate cancer, the benefit of TB may be obscured by the high percentage of such lesions in this study. Second, SB technique plays a critical role in determining outcomes. Freehand biopsy may have its own inherent biases compared to computer-generated biopsy templates, especially when the operator is unblinded to the location of the lesion, as was the case in this study. Third, as for many aspects of our specialty, surgeon experience and volume have a significant impact on outcomes, and this study represents the earlier part of the learning curve, as evidenced by the higher rate of positive right-sided targets, whereas our institution is further along that curve. In addition to surgeon experience, radiologist experience is crucial owing to the complexity of mpMRI. The authors allude to this, as they mention the potential limitation of inter-reader variability for mpMRI interpretation, and while their study included multiple radiologists with a range of experience, our studies relied on only two highly experienced radiologists. Finally, a
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2016.05.021. * Corresponding author. Department of Urology, University of California at Los Angeles, 300 Stein Way, Los Angeles, CA 90095, USA. Tel. +1 310 7947224; Fax: +1 310 2065343. E-mail address: [email protected] (R.E. Reiter). http://dx.doi.org/10.1016/j.eururo.2016.05.048 0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Prado K, Reiter RE. Is Targeted Biopsy Applicable to Patients on Active Surveillance? Eur Urol (2016), http://dx.doi.org/10.1016/j.eururo.2016.05.048
EURURO-6854; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2016) XXX–XXX
limitation not addressed by this study is the anterior lesion distribution, which is more likely to yield clinically significant cancers [7]. The relative paucity of such lesions in their AS or confirmatory biopsy patients might have contributed to the poor performance of TB compared to SB in their study. While the study diverges from our findings and those of others with respect to the correlation between PIRADS and clinically significant prostate cancer in AS patients, it confirms prior studies demonstrating a benefit for TB in the diagnostic setting. Our analysis of all patients undergoing TB with at least one PIRADS 3 lesion demonstrated a significantly higher number of GS 7 cases identified when TB is combined with SB (378/825, 45.8%) compared to SB alone (250/825, 30.3%) [6], similar to the findings in this study. However, we also observed a higher number of GS 7 cases among patients with at least one PIRADS 3 lesion when comparing TB alone to SB alone (303/825, 36.7% vs 250/825, 30.3%), whereas Ma et al observed a lower number (41/73, 56.1% vs 43/73, 58.9%) in the diagnostic setting. Their study also demonstrated a statistically significant correlation between PIRADS score and detection of clinically significant prostate cancer in the diagnostic setting, albeit to a lesser degree than in our study. One important but controversial finding by Ma et al is that SB in all settings identifies a substantial number of significant tumors not identified by TB. This general finding is in agreement with our own studies, which demonstrated that 20% of significant tumors are MRI-invisible (confirmed by comparison of mpMRI with whole-mount prostatectomy specimens) [8] and that combining SB and TB yields the highest number of such tumors in all populations studied. PSA density >0.15 is a strong independent predictor of the presence of significant cancers in men with negative MRI and might be used to determine which patients with normal MRI need biopsy [9,10]. In summary, the study by Ma et al confirms that TB in combination with SB may be beneficial in the diagnostic setting; however its role in the AS population may be lesser
given the prevalence of PIRADS 3 lesions in this population. Given the strict eligibility criteria for AS in this study, the findings may not be generalized to all AS protocols. Thus, further studies incorporating mpMRI and TB are warranted. Conflicts of interest: The authors have nothing to disclose. References [1] Ma TM, Tosoian JJ, Schaeffer EM, et al. The role of multiparametric magnetic resonance imaging/ultrasound fusion biopsy in active surveillance. Eur Urol. In press. http://dx.doi.org/10.1016/j. eururo.2016.05.021. [2] Walton Diaz A, Shakir NA, George AK, et al. Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance. Urol Oncol Semin Orig Investig 2015;33:202e1–7e. [3] Mendhiratta N, Rosenkrantz AB, Meng X, 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. J Urol 2015;194: 1601–6. [4] Ouzzane A, Renard-Penna R, Marliere F, et al. Magnetic resonance imaging targeted biopsy improves selection of patients considered for active surveillance for clinically low risk prostate cancer based on systematic biopsies. J Urol 2015;194:350–6. [5] Hu JC, Chang E, Natarajan S, et al. Targeted prostate biopsy in select men for active surveillance — do the Epstein criteria still apply? J Urol 2014;192:385–90. [6] Filson CP, Natarajan S, Margolis DJA, et al. Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: the role of systematic and targeted biopsies. Cancer 2016;122:884–92. [7] Ouzzane A, Puech P, Lemaitre L, et al. Combined multiparametric MRI and targeted biopsies improve anterior prostate cancer detection, staging, and grading. Urology 2011;78:1356–62. [8] Le JD, Stephenson S, Brugger M, et al. Magnetic resonance imagingultrasound fusion biopsy for prediction of final prostate pathology. J Urol 2014;192:1367–73. [9] Chamie K, Sonn GA, Finley DS, et al. The role of magnetic resonance imaging in delineating clinically significant prostate cancer. Urology 2014;83:369–75. [10] Felker ER, Wu J, Natarajan S, , et al. Serial MRI. in active surveillance of prostate cancer: incremental value. J Urol 2015;195:1421–7.
Please cite this article in press as: Prado K, Reiter RE. Is Targeted Biopsy Applicable to Patients on Active Surveillance? Eur Urol (2016), http://dx.doi.org/10.1016/j.eururo.2016.05.048
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority Referring to the article published on pp. x–y of this issue
Is Targeted Biopsy Applicable to Patients on Active Surveillance? Kris Prado a, Robert E. Reiter a,b,* a
Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; b Institute of Urologic Oncology,
Los Angeles, CA, USA
Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) hold the promise of added precision in our approach to staging and classification of prostate cancer. In this issue of European Urology, Ma and colleagues [1] examine the utility of this diagnostic modality in the active surveillance (AS) population. They demonstrate that among patients enrolled in AS at their institution, addition of TB to systematic biopsy (SB) does not add significant benefit in terms of reclassifying patients on confirmatory biopsy or detecting higher-grade disease while on AS. Rather, SB resulted in identification of higher-grade disease more often than TB in the AS cohort: TB led to the diagnosis of Gleason score (GS) 7 in 7/103 patients (6.8%), while SB diagnosed GS 7 in 21/103 patients (20.4%). When combined, TB and SB diagnosed GS 7 in 25/103 patients (24.2%). Despite the lack of benefit in detecting highergrade disease in patients on AS, the authors did identify a number of patients with GS 7 disease detected by combining TB and SB as opposed to SB alone in patients undergoing confirmatory biopsy or presenting for initial biopsy (statistically significant): 3/54 patients (5.5%) in the confirmatory biopsy group and 12/73 patients in the diagnostic biopsy group (16.4%). This study contrasts with investigations in our institution and others [2–4] supporting the utility of mpMRI and TB in the AS population. Hu and colleagues [5] demonstrated that the presence of Prostate Imaging-Reporting and Data System (PIRADS) 4 and 5 lesions in AS patients undergoing confirmatory biopsy resulted in a high rate of reclassification (47% and 100%, respectively) beyond the Epstein criteria. In addition, Filson and colleagues [6] demonstrated that the presence of a PIRADS 3 lesion was a poor predictor of clinically significant prostate cancer, and
reiterated the strong association between PIRADS 4/5 lesions and clinically significant prostate cancer in the confirmatory biopsy setting. The study by Ma et al shows only a modest association between PIRADS 4/5 lesions and clinically significant prostate cancer in the confirmatory biopsy setting, and no association in the AS setting. Several factors can explain this discrepancy. First, the patient population studied by Ma et al is smaller and based on stricter eligibility criteria for AS (very low-risk prostate cancer) compared to our institution. The incidence of PIRADS 3 lesions among the confirmatory biopsy group (48%) and the AS group (58%) was higher than what we have observed for patients being considered for AS (41%) [6]. Since these lesions correlate poorly with clinically significant prostate cancer, the benefit of TB may be obscured by the high percentage of such lesions in this study. Second, SB technique plays a critical role in determining outcomes. Freehand biopsy may have its own inherent biases compared to computer-generated biopsy templates, especially when the operator is unblinded to the location of the lesion, as was the case in this study. Third, as for many aspects of our specialty, surgeon experience and volume have a significant impact on outcomes, and this study represents the earlier part of the learning curve, as evidenced by the higher rate of positive right-sided targets, whereas our institution is further along that curve. In addition to surgeon experience, radiologist experience is crucial owing to the complexity of mpMRI. The authors allude to this, as they mention the potential limitation of inter-reader variability for mpMRI interpretation, and while their study included multiple radiologists with a range of experience, our studies relied on only two highly experienced radiologists. Finally, a
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2016.05.021. * Corresponding author. Department of Urology, University of California at Los Angeles, 300 Stein Way, Los Angeles, CA 90095, USA. Tel. +1 310 7947224; Fax: +1 310 2065343. E-mail address: [email protected] (R.E. Reiter). http://dx.doi.org/10.1016/j.eururo.2016.05.048 0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Prado K, Reiter RE. Is Targeted Biopsy Applicable to Patients on Active Surveillance? Eur Urol (2016), http://dx.doi.org/10.1016/j.eururo.2016.05.048
EURURO-6854; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2016) XXX–XXX
limitation not addressed by this study is the anterior lesion distribution, which is more likely to yield clinically significant cancers [7]. The relative paucity of such lesions in their AS or confirmatory biopsy patients might have contributed to the poor performance of TB compared to SB in their study. While the study diverges from our findings and those of others with respect to the correlation between PIRADS and clinically significant prostate cancer in AS patients, it confirms prior studies demonstrating a benefit for TB in the diagnostic setting. Our analysis of all patients undergoing TB with at least one PIRADS 3 lesion demonstrated a significantly higher number of GS 7 cases identified when TB is combined with SB (378/825, 45.8%) compared to SB alone (250/825, 30.3%) [6], similar to the findings in this study. However, we also observed a higher number of GS 7 cases among patients with at least one PIRADS 3 lesion when comparing TB alone to SB alone (303/825, 36.7% vs 250/825, 30.3%), whereas Ma et al observed a lower number (41/73, 56.1% vs 43/73, 58.9%) in the diagnostic setting. Their study also demonstrated a statistically significant correlation between PIRADS score and detection of clinically significant prostate cancer in the diagnostic setting, albeit to a lesser degree than in our study. One important but controversial finding by Ma et al is that SB in all settings identifies a substantial number of significant tumors not identified by TB. This general finding is in agreement with our own studies, which demonstrated that 20% of significant tumors are MRI-invisible (confirmed by comparison of mpMRI with whole-mount prostatectomy specimens) [8] and that combining SB and TB yields the highest number of such tumors in all populations studied. PSA density >0.15 is a strong independent predictor of the presence of significant cancers in men with negative MRI and might be used to determine which patients with normal MRI need biopsy [9,10]. In summary, the study by Ma et al confirms that TB in combination with SB may be beneficial in the diagnostic setting; however its role in the AS population may be lesser
given the prevalence of PIRADS 3 lesions in this population. Given the strict eligibility criteria for AS in this study, the findings may not be generalized to all AS protocols. Thus, further studies incorporating mpMRI and TB are warranted. Conflicts of interest: The authors have nothing to disclose. References [1] Ma TM, Tosoian JJ, Schaeffer EM, et al. The role of multiparametric magnetic resonance imaging/ultrasound fusion biopsy in active surveillance. Eur Urol. In press. http://dx.doi.org/10.1016/j. eururo.2016.05.021. [2] Walton Diaz A, Shakir NA, George AK, et al. Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance. Urol Oncol Semin Orig Investig 2015;33:202e1–7e. [3] Mendhiratta N, Rosenkrantz AB, Meng X, 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. J Urol 2015;194: 1601–6. [4] Ouzzane A, Renard-Penna R, Marliere F, et al. Magnetic resonance imaging targeted biopsy improves selection of patients considered for active surveillance for clinically low risk prostate cancer based on systematic biopsies. J Urol 2015;194:350–6. [5] Hu JC, Chang E, Natarajan S, et al. Targeted prostate biopsy in select men for active surveillance — do the Epstein criteria still apply? J Urol 2014;192:385–90. [6] Filson CP, Natarajan S, Margolis DJA, et al. Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: the role of systematic and targeted biopsies. Cancer 2016;122:884–92. [7] Ouzzane A, Puech P, Lemaitre L, et al. Combined multiparametric MRI and targeted biopsies improve anterior prostate cancer detection, staging, and grading. Urology 2011;78:1356–62. [8] Le JD, Stephenson S, Brugger M, et al. Magnetic resonance imagingultrasound fusion biopsy for prediction of final prostate pathology. J Urol 2014;192:1367–73. [9] Chamie K, Sonn GA, Finley DS, et al. The role of magnetic resonance imaging in delineating clinically significant prostate cancer. Urology 2014;83:369–75. [10] Felker ER, Wu J, Natarajan S, , et al. Serial MRI. in active surveillance of prostate cancer: incremental value. J Urol 2015;195:1421–7.
Please cite this article in press as: Prado K, Reiter RE. Is Targeted Biopsy Applicable to Patients on Active Surveillance? Eur Urol (2016), http://dx.doi.org/10.1016/j.eururo.2016.05.048