- Email: [email protected]
Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer
Clinical Oncology xxx (xxxx) xxx Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer R.J. Chuang, L.S. Marks Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, California, USA Received 11 September 2019; received in revised form 22 November 2019; accepted 29 November 2019
Abstract The value of multi-parametric magnetic resonance imaging in the detection of clinically-significant prostate cancer is increasingly well-established, and has been adopted in current diagnostic pathways and clinical guidelines. Concurrently, the role of conventional ultrasound-guided systematic prostate biopsy is increasingly questioned. In this brief review, we evaluate the continued value of systematic biopsy including a review of prospective studies on targeted and systemic biopsies in the same patients. We also address current limitations of multi-parametric magnetic resonance imaging of the prostate. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Key words: Multi-parametric magnetic resonance imaging; prostate cancer; targeted biopsy
The value of multiparametric magnetic resonance imaging (mpMRI) in the detection of clinically significant prostate cancer (csCaP) has been established by studies such as the PROMIS and PRECISION trials. As prostate mpMRI is adopted in diagnostic pathways and clinical guidelines, the role of conventional ultrasound-guided systematic biopsy, with its risk of significant morbidity including sepsis, is increasingly questioned [1,2]. Here, we evaluate the continued value of systematic biopsy and current limitations of mpMRI in this rapidly developing world of targeted biopsy. As independent diagnostic methods, mpMRI-guided targeted and systematic biopsy each has the potential to identify tumours in disparate locations (Figure 1). In addition, the rate of detection of even the same tumours may differ based on reading and contouring of the mpMRI and suspicious regions of interest, individual performance variation in biopsy technique, and timing and sequence of combined biopsies. In the PROMIS study, Ahmed et al. [1] evaluated mpMRI in comparison with template prostate
Address for correspondence: L.S. Marks, Department of Urology, David Geffen School of Medicine, University of California, 10944 Le Conte Ave, Los Angeles, CA, 90095, USA. Tel: þ1-310-794-3070. E-mail address: [email protected] (L.S. Marks).
Fig 1. Schematic of systematic and targeted prostate biopsies. Reconstructed images from fusion device showing biopsy approaches. A region of interest from the magnetic resonance image is shown in grey. In the systematic biopsies (blue), one core is found to contain cancer (A). Within the region of interest, three targeted biopsy cores are taken (purple), in which one also contains cancer (B).
https://doi.org/10.1016/j.clon.2019.11.011 0936-6555/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
2
First author (nation of origin; trial)
Year ny published
Arsov (Germany)
2015
104/210 RCT
Baco (Norway)
2016
86/175
Tontilla (Finland)
2016
Taverna (Italy)
2016
Elkhoury 2019 (United States; PAIREDCAP) Miah (England) 2019
Study Method of design targeting
Fusion system (Company)
Detection rate: Detection rate: Added Definition of targeted combined detection clinically significant of csCaP (%)
Fusion
Urostation (Koelis)
27/104
33/104
6/104 (6)
GG 2
RCT
Fusion
Urostation (Koelis)
33/86
38/86
5/86 (6)
GG 1 or GG 1 with MCCL 5 mm
53/113
RCT
Cognitive
n/a
22/53
29/53
7/53 (13)
100
RCT
Cognitive
n/a
8/100
15/100
7/100 (7)
Artemis (Eigen)
154/248
174/248
20/248 (8)
GG 2, >2 positive cores or MCCL 3 mm GG 2 or any cancer Subgroup core length > 5 mm analysis of RCT between SB only versus MRI þ SB GG 2 Biopsy-naïve
248/300 Paired Cognitive cohort and fusion 640
Paired Fusion* cohort
Symphony Dx (MIM Software)
263/640
276/640
13/640 (2)
GG 3 or any grade with core length 6 mm
re Rouvie 2019 (France; MRI-FIRST)
251
RCT
105/251
15/251 (6)
van der Leest (Netherlands)
317/626 Paired In-bore cohort MRI-guided
Urostation (Koelis), 90/251 Applio 500 (Toshiba) Percunav (Philips) In-bore (Invivo) 159/317
180/317
21/317 (7)
GG 1 with MCCL 6 mm or GG 2 GG 2
2019
Cognitive or fusion
Comments
Study halted primary end point not met First RCT comparing detection rates in fusion TB versus SB in biopsy-naïve Biopsy-naïve
Largest multicentre study of transperineal fusion TB to-date Biopsy-naïve
Biopsy-naïve
GG, Gleason grade group; MCCL, maximum cancer core length; RCT, randomised controlled trial (paired diagnostic); SB, systematic biopsy; TB, targeted biopsy; TRUS, transrectal ultrasound. * Transperineal. y Number of patients undergoing both targeted and systematic biopsy/total patients enrolled in study.
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
Table 1 Detection of clinically significant prostate cancer (csCaP) in prospective studies pairing multiparametric magnetic resonance imaging (mpMRI) targeted and systematic prostate biopsy in the same patients
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
mapping biopsy, a more extensive version of systematic biopsy with cores taken every 5 mm. The authors found that mpMRI had a negative predictive value of 76% (95% confidence interval 69e82%) for International Society of Urological Pathology (ISUP) grade group 2 or higher cancers, suggesting that a solely mpMRI-guided diagnostic pathway may not be sufficient in the diagnosis of csCaP. In addition, of the 158 men who had a negative mpMRI, 17 (11%) had csCaP on mapping biopsy. In the PRECISION trial, Kasivisvanathan et al. [2] found that csCaP was detected in 38% of targeted biopsies compared with 26% of systematic biopsies (P ¼ 0.005). Other studies comparing targeted with systematic biopsy have found similar higher rates of csCaP detection by targeted biopsy, with a recent meta-analysis of 68 paired cohort studies and eight randomised controlled trials revealing a targeted to systematic biopsy detection ratio of 1.16 (95% confidence interval 1.09e1.24) [3]. However, in PRECISION and many of these other studies, systematic biopsy was not utilised in the targeted biopsy arm, leaving the value of systematic biopsy in combination with targeted biopsy unclear.
Detection of csCaP is Maximised when Combining Targeted with Systematic Biopsy We carried out a comprehensive review of the published literature of prospective studies comparing targeted biopsy to systematic biopsy in the same patients (Table 1). As previous reviews have revealed limitations in study design and samples, these criteria were selected to ensure that relevant comparisons were made and intra-study variability was minimised. We found that the addition of systematic biopsy to targeted biopsy resulted in the diagnosis of an additional 2e13% of csCaP that would have been missed by targeted biopsy alone. Below we highlight key studies from Table 1. In the PAIREDCAP trial, Elkhoury et al. [4] sought to compare different biopsy methods in the same patients. In a prospective paired cohort study of 248 biopsy-naive men with MRI-visible lesions, a systematic biopsy was carried out followed by cognitive and fusion targeted biopsy. The authors detected csCaP in 70.2% of patients, the high rate of which they attributed to a cancer-enriched, MRI-screened population. They found no significant difference in csCaP detection rate between biopsy methods, with 47%, 54% and 60% of cognitive targeted biopsy, cognitive or fusion targeted biopsy, and systematic biopsy detecting csCaP. When combining both systematic and targeted biopsy, the detection rate of csCaP increased to 70%. MRI-FIRST was a multicentre, prospective, paired diagnostic study in which participants were free to use their own mpMRI protocol and approach for targeted biopsy [5]. This approach intentionally introduced heterogeneity to reflect routine practice. In this study, of 251 men who
3
underwent both biopsy methods, csCaP was detected in 36% of target biopsies and 33% of systematic biopsies. csCaP was detected exclusively by systematic biopsy in 6% of patients. re et al. [5] found no difference in detection of csCaP Rouvie between targeted biopsy and systematic biopsy. The authors concluded that, taken together with the results of the PRECISION trial, detection rates of csCaP were improved when both biopsy methods were combined. This conclusion was nuanced by the note that the added value of systematic biopsy was marginalised when looking exclusively at grade group 3 or higher tumours (csPCa-C). Miah et al. sought to ascertain the utility of systematic biopsy exclusively using transperineal biopsies, an alternative approach to transrectal biopsies that may avoid dissemination of bacteria into the prostate and decrease infection rates [6,7]. In this multicentre cohort study, the authors found csCaP in 9.0% of systematic biopsies and 41% of targeted biopsies. They concluded that transperineal systematic biopsies detected only 1% additional csCaP. No standardised template or protocol was used for either targeted or systematic biopsy, and some physicians carried out target biopsies only according to local practice. Interestingly, the other lowest rate of additional csCaP diagnosis was also found in a study using transperineal biopsy [8]. By contrast, the highest rate of additional csCaP detection by systematic biopsy at 13% was found by Tonttila et al. [9]. In this single-centre study, the authors' explicit aim was to evaluate the diagnostic value of mpMRI in a hospital-based practice setting instead of at centres of excellence for prostate MRI. Radiologists involved in this trial were experienced in full-body but not prostate MRI. Cognitive fusion was used exclusively. Van der Leest and colleagues [10] examined the detection rate difference between yet another method, comparing in-bore MRI-guided target biopsy with systematic biopsy. In their multicentre study, they found no significant difference in the detection of csCaP, with a 25 and 23% detection rate in targeted and systematic biopsy, respectively. The authors also found no significant difference in the detection of higher grade, greater or equal than Gleason grade group 3, cancer.
Patients without Observed Suspicious Lesions on mpMRI May Still Harbour csCaP. Variability in Inter-observer Reproducibility Precludes MRI from Being the Sole Diagnostic Method The PROMIS study highlighted the insufficiency of mpMRI as the sole diagnostic pathway for csCaP. Similar findings are present in other studies comparing targeted biopsy with systematic biopsy. In MRI-FIRST, systematic biopsy detected csCaP in five (11%) of the 45 patients with negative mpMRI [5]. Tonttila et al. [9] found that three of 13 MRI-negative patients had grade group 2 cancer. What
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
4
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
may account for these undetected csCaP? In the PAIREDCAP trial, on further investigation, Elkhoury et al. [4] found that significant discordance between prostate gland sidedness of csCaP existed between targeted and systematic biopsy, suggesting that not all csCaP was within MRIvisible areas. By contrast, van der Leest et al. [10] found that in the 21 patients in which csCaP was not detected by targeted biopsy but was found on systematic biopsy, 20 of these patients harboured lesions suspicious on mpMRI, and that the positive cores on systematic biopsy were taken from either the region of the suspicious lesion or areas peripheral to it. On retrospective MRI reading, the remaining patient was also found to have a suspicious lesion. The authors concluded that ‘the majority of csCaP missed by MR-guided biopsy appears to be sampling errors related to intratumor heterogeneity’. The authors acknowledged finding PI-RADSv2 3 lesions in only 6% of their patients, in comparison with 21 and 28% in the PROMIS and PRECISION trials, which they attributed to the use of ‘double-expert consensus’ in MRI reading, although other studies with similar multiple readers did not show such low rates of PI-RADSv2 3 lesions. Further investigation is warranted. In 2017, Priester et al. [11] carried out a study of 114 men who underwent radical prostatectomy, comparing their preoperative MRI with the resultant whole mount pathology placed in the same orientation using 3D-printed patient-specific moulds. The authors found that even from contours created by experienced radiologists, the average tumour diameter was underestimated by 1.1 cm, with a median extension of actual tumour length 1.4 cm beyond the contours of the marked region of interest. Other studies also indicated a degree of tumour size underestimation. Even in the periphery of MRI-suspicious lesions, a degree of uncertainty exists. Finally, in a retrospective study between six different radiologists at six separate institutions experienced in reading prostate MRIs, Rosenkrantz et al. reported a k coefficient of 0.46 for the determination of PIRADSv2 lesions 3, indicating moderate agreement over random chance [12,13]. As discussed in their study, although this is comparable with other cancer reporting systems including BI-RADS in breast cancer studies, this k coefficient indicates that considerable inter-reader variation still exists. In addition, even after a 2-week training session, the authors found no improvement in reproducibility, which they hypothesised may foretell a potential limit to the degree of achievable reproducibility. In summary, although MRI-targeted biopsy improves the detection of clinically significant disease, it does not yet obviate the need for systematic biopsy. Data from Zhou [14] have indicated that the use of a standard device-guided templating system may further improve the rate of detection of csCaP over current user-guided systematic biopsy. As the development of novel methods for obtaining biopsies and the determination of an optimal biopsy protocol are both still underway, there still remains a role for the combined use of systematic biopsy.
Conflict of Interest L. Marks is co-founder of Avenda Health Inc., a biomedical device company aiming to treat prostate tumours focally with a laser device.
References [1] Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017;389:815e822. [2] Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. New Engl J Med 2018; 378:1767e1777. [3] Kasivisvanathan V, Stabile A, Neves JB, Giganti F, Valerio M, Shanmugabavan Y, et al. Magnetic resonance imagingtargeted biopsy versus systematic biopsy in the detection of prostate cancer: a systematic review and meta-analysis. Eur Urol 2019;76:284e303. [4] Elkhoury FF, Felker ER, Kwan L, Sisk AE, Delfin M, Natarajan S, et al. Comparison of targeted vs systematic prostate biopsy in men who are biopsy naive: the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study. JAMA Surg 2019;154(9):811e818. [5] Rouviere O, Puech P, Renard-Penna R, Claudon M, Roy C, Mege-Lechevallier F, et al. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol 2019;20:100e109. [6] Kuru TH, Wadhwa K, Chang RT, Echeverria LM, Roethke M, Polson A, et al. Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg study group for enhanced prostate diagnostics. BJU Int 2013;112:568e577. [7] Miah S, Hosking-Jervis F, Connor MJ, Eldred-Evans D, Shah TT, Arya M, et al. A multicentre analysis of the detection of clinically significant prostate cancer following transperineal image-fusion targeted and nontargeted systematic prostate biopsy in men at risk. Eur Urol Oncol 2019. https://doi.org/10. 1016/j.euo.2019.03.005. [8] Borkowetz A, Platzek I, Toma M, Laniado M, Baretton G, Froehner M, et al. Comparison of systematic transrectal biopsy to transperineal magnetic resonance imaging/ultrasoundfusion biopsy for the diagnosis of prostate cancer. BJU Int 2015;116:873e879. [9] Tonttila PP, Lantto J, Paakko E, Piippo U, Kauppila S, Lammentausta E, et al. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsynaive men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. Eur Urol 2016; 69:419e425. [10] van der Leest M, Cornel E, Israel B, Hendriks R, Padhani AR, Hoogenboom M, et al. Head-to-head comparison of transrectal ultrasound-guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance-guided biopsy in biopsy-naive men with elevated prostate-specific antigen: a large prospective multicenter clinical study. Eur Urol 2019;75:570e578. [11] Priester A, Natarajan S, Khoshnoodi P, Margolis DJ, Raman SS, Reiter RE, et al. Magnetic resonance imaging underestimation
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx of prostate cancer geometry: use of patient specific molds to correlate images with whole mount pathology. J Urol 2017; 197:320e326. [12] Rosenkrantz AB, Ginocchio LA, Cornfeld D, Froemming AT, Gupta RT, Turkbey B, et al. Interobserver reproducibility of the PI-RADS Version 2 Lexicon: a multicenter study of six experienced prostate radiologists. Radiology 2016;280:793e804.
5
[13] McHugh ML. Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 2012;22:276e282. [14] Zhou SR, et al. Prostate cancer detection rate of free-hand versus 3D template mapping biopsy using an MRI/ultrasound fusion device in biopsy-naïve men. J Urol 2019. https://doi. org/10.1097/JU.0000000000000587.
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer R.J. Chuang, L.S. Marks Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, California, USA Received 11 September 2019; received in revised form 22 November 2019; accepted 29 November 2019
Abstract The value of multi-parametric magnetic resonance imaging in the detection of clinically-significant prostate cancer is increasingly well-established, and has been adopted in current diagnostic pathways and clinical guidelines. Concurrently, the role of conventional ultrasound-guided systematic prostate biopsy is increasingly questioned. In this brief review, we evaluate the continued value of systematic biopsy including a review of prospective studies on targeted and systemic biopsies in the same patients. We also address current limitations of multi-parametric magnetic resonance imaging of the prostate. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Key words: Multi-parametric magnetic resonance imaging; prostate cancer; targeted biopsy
The value of multiparametric magnetic resonance imaging (mpMRI) in the detection of clinically significant prostate cancer (csCaP) has been established by studies such as the PROMIS and PRECISION trials. As prostate mpMRI is adopted in diagnostic pathways and clinical guidelines, the role of conventional ultrasound-guided systematic biopsy, with its risk of significant morbidity including sepsis, is increasingly questioned [1,2]. Here, we evaluate the continued value of systematic biopsy and current limitations of mpMRI in this rapidly developing world of targeted biopsy. As independent diagnostic methods, mpMRI-guided targeted and systematic biopsy each has the potential to identify tumours in disparate locations (Figure 1). In addition, the rate of detection of even the same tumours may differ based on reading and contouring of the mpMRI and suspicious regions of interest, individual performance variation in biopsy technique, and timing and sequence of combined biopsies. In the PROMIS study, Ahmed et al. [1] evaluated mpMRI in comparison with template prostate
Address for correspondence: L.S. Marks, Department of Urology, David Geffen School of Medicine, University of California, 10944 Le Conte Ave, Los Angeles, CA, 90095, USA. Tel: þ1-310-794-3070. E-mail address: [email protected] (L.S. Marks).
Fig 1. Schematic of systematic and targeted prostate biopsies. Reconstructed images from fusion device showing biopsy approaches. A region of interest from the magnetic resonance image is shown in grey. In the systematic biopsies (blue), one core is found to contain cancer (A). Within the region of interest, three targeted biopsy cores are taken (purple), in which one also contains cancer (B).
https://doi.org/10.1016/j.clon.2019.11.011 0936-6555/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
2
First author (nation of origin; trial)
Year ny published
Arsov (Germany)
2015
104/210 RCT
Baco (Norway)
2016
86/175
Tontilla (Finland)
2016
Taverna (Italy)
2016
Elkhoury 2019 (United States; PAIREDCAP) Miah (England) 2019
Study Method of design targeting
Fusion system (Company)
Detection rate: Detection rate: Added Definition of targeted combined detection clinically significant of csCaP (%)
Fusion
Urostation (Koelis)
27/104
33/104
6/104 (6)
GG 2
RCT
Fusion
Urostation (Koelis)
33/86
38/86
5/86 (6)
GG 1 or GG 1 with MCCL 5 mm
53/113
RCT
Cognitive
n/a
22/53
29/53
7/53 (13)
100
RCT
Cognitive
n/a
8/100
15/100
7/100 (7)
Artemis (Eigen)
154/248
174/248
20/248 (8)
GG 2, >2 positive cores or MCCL 3 mm GG 2 or any cancer Subgroup core length > 5 mm analysis of RCT between SB only versus MRI þ SB GG 2 Biopsy-naïve
248/300 Paired Cognitive cohort and fusion 640
Paired Fusion* cohort
Symphony Dx (MIM Software)
263/640
276/640
13/640 (2)
GG 3 or any grade with core length 6 mm
re Rouvie 2019 (France; MRI-FIRST)
251
RCT
105/251
15/251 (6)
van der Leest (Netherlands)
317/626 Paired In-bore cohort MRI-guided
Urostation (Koelis), 90/251 Applio 500 (Toshiba) Percunav (Philips) In-bore (Invivo) 159/317
180/317
21/317 (7)
GG 1 with MCCL 6 mm or GG 2 GG 2
2019
Cognitive or fusion
Comments
Study halted primary end point not met First RCT comparing detection rates in fusion TB versus SB in biopsy-naïve Biopsy-naïve
Largest multicentre study of transperineal fusion TB to-date Biopsy-naïve
Biopsy-naïve
GG, Gleason grade group; MCCL, maximum cancer core length; RCT, randomised controlled trial (paired diagnostic); SB, systematic biopsy; TB, targeted biopsy; TRUS, transrectal ultrasound. * Transperineal. y Number of patients undergoing both targeted and systematic biopsy/total patients enrolled in study.
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
Table 1 Detection of clinically significant prostate cancer (csCaP) in prospective studies pairing multiparametric magnetic resonance imaging (mpMRI) targeted and systematic prostate biopsy in the same patients
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
mapping biopsy, a more extensive version of systematic biopsy with cores taken every 5 mm. The authors found that mpMRI had a negative predictive value of 76% (95% confidence interval 69e82%) for International Society of Urological Pathology (ISUP) grade group 2 or higher cancers, suggesting that a solely mpMRI-guided diagnostic pathway may not be sufficient in the diagnosis of csCaP. In addition, of the 158 men who had a negative mpMRI, 17 (11%) had csCaP on mapping biopsy. In the PRECISION trial, Kasivisvanathan et al. [2] found that csCaP was detected in 38% of targeted biopsies compared with 26% of systematic biopsies (P ¼ 0.005). Other studies comparing targeted with systematic biopsy have found similar higher rates of csCaP detection by targeted biopsy, with a recent meta-analysis of 68 paired cohort studies and eight randomised controlled trials revealing a targeted to systematic biopsy detection ratio of 1.16 (95% confidence interval 1.09e1.24) [3]. However, in PRECISION and many of these other studies, systematic biopsy was not utilised in the targeted biopsy arm, leaving the value of systematic biopsy in combination with targeted biopsy unclear.
Detection of csCaP is Maximised when Combining Targeted with Systematic Biopsy We carried out a comprehensive review of the published literature of prospective studies comparing targeted biopsy to systematic biopsy in the same patients (Table 1). As previous reviews have revealed limitations in study design and samples, these criteria were selected to ensure that relevant comparisons were made and intra-study variability was minimised. We found that the addition of systematic biopsy to targeted biopsy resulted in the diagnosis of an additional 2e13% of csCaP that would have been missed by targeted biopsy alone. Below we highlight key studies from Table 1. In the PAIREDCAP trial, Elkhoury et al. [4] sought to compare different biopsy methods in the same patients. In a prospective paired cohort study of 248 biopsy-naive men with MRI-visible lesions, a systematic biopsy was carried out followed by cognitive and fusion targeted biopsy. The authors detected csCaP in 70.2% of patients, the high rate of which they attributed to a cancer-enriched, MRI-screened population. They found no significant difference in csCaP detection rate between biopsy methods, with 47%, 54% and 60% of cognitive targeted biopsy, cognitive or fusion targeted biopsy, and systematic biopsy detecting csCaP. When combining both systematic and targeted biopsy, the detection rate of csCaP increased to 70%. MRI-FIRST was a multicentre, prospective, paired diagnostic study in which participants were free to use their own mpMRI protocol and approach for targeted biopsy [5]. This approach intentionally introduced heterogeneity to reflect routine practice. In this study, of 251 men who
3
underwent both biopsy methods, csCaP was detected in 36% of target biopsies and 33% of systematic biopsies. csCaP was detected exclusively by systematic biopsy in 6% of patients. re et al. [5] found no difference in detection of csCaP Rouvie between targeted biopsy and systematic biopsy. The authors concluded that, taken together with the results of the PRECISION trial, detection rates of csCaP were improved when both biopsy methods were combined. This conclusion was nuanced by the note that the added value of systematic biopsy was marginalised when looking exclusively at grade group 3 or higher tumours (csPCa-C). Miah et al. sought to ascertain the utility of systematic biopsy exclusively using transperineal biopsies, an alternative approach to transrectal biopsies that may avoid dissemination of bacteria into the prostate and decrease infection rates [6,7]. In this multicentre cohort study, the authors found csCaP in 9.0% of systematic biopsies and 41% of targeted biopsies. They concluded that transperineal systematic biopsies detected only 1% additional csCaP. No standardised template or protocol was used for either targeted or systematic biopsy, and some physicians carried out target biopsies only according to local practice. Interestingly, the other lowest rate of additional csCaP diagnosis was also found in a study using transperineal biopsy [8]. By contrast, the highest rate of additional csCaP detection by systematic biopsy at 13% was found by Tonttila et al. [9]. In this single-centre study, the authors' explicit aim was to evaluate the diagnostic value of mpMRI in a hospital-based practice setting instead of at centres of excellence for prostate MRI. Radiologists involved in this trial were experienced in full-body but not prostate MRI. Cognitive fusion was used exclusively. Van der Leest and colleagues [10] examined the detection rate difference between yet another method, comparing in-bore MRI-guided target biopsy with systematic biopsy. In their multicentre study, they found no significant difference in the detection of csCaP, with a 25 and 23% detection rate in targeted and systematic biopsy, respectively. The authors also found no significant difference in the detection of higher grade, greater or equal than Gleason grade group 3, cancer.
Patients without Observed Suspicious Lesions on mpMRI May Still Harbour csCaP. Variability in Inter-observer Reproducibility Precludes MRI from Being the Sole Diagnostic Method The PROMIS study highlighted the insufficiency of mpMRI as the sole diagnostic pathway for csCaP. Similar findings are present in other studies comparing targeted biopsy with systematic biopsy. In MRI-FIRST, systematic biopsy detected csCaP in five (11%) of the 45 patients with negative mpMRI [5]. Tonttila et al. [9] found that three of 13 MRI-negative patients had grade group 2 cancer. What
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
4
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx
may account for these undetected csCaP? In the PAIREDCAP trial, on further investigation, Elkhoury et al. [4] found that significant discordance between prostate gland sidedness of csCaP existed between targeted and systematic biopsy, suggesting that not all csCaP was within MRIvisible areas. By contrast, van der Leest et al. [10] found that in the 21 patients in which csCaP was not detected by targeted biopsy but was found on systematic biopsy, 20 of these patients harboured lesions suspicious on mpMRI, and that the positive cores on systematic biopsy were taken from either the region of the suspicious lesion or areas peripheral to it. On retrospective MRI reading, the remaining patient was also found to have a suspicious lesion. The authors concluded that ‘the majority of csCaP missed by MR-guided biopsy appears to be sampling errors related to intratumor heterogeneity’. The authors acknowledged finding PI-RADSv2 3 lesions in only 6% of their patients, in comparison with 21 and 28% in the PROMIS and PRECISION trials, which they attributed to the use of ‘double-expert consensus’ in MRI reading, although other studies with similar multiple readers did not show such low rates of PI-RADSv2 3 lesions. Further investigation is warranted. In 2017, Priester et al. [11] carried out a study of 114 men who underwent radical prostatectomy, comparing their preoperative MRI with the resultant whole mount pathology placed in the same orientation using 3D-printed patient-specific moulds. The authors found that even from contours created by experienced radiologists, the average tumour diameter was underestimated by 1.1 cm, with a median extension of actual tumour length 1.4 cm beyond the contours of the marked region of interest. Other studies also indicated a degree of tumour size underestimation. Even in the periphery of MRI-suspicious lesions, a degree of uncertainty exists. Finally, in a retrospective study between six different radiologists at six separate institutions experienced in reading prostate MRIs, Rosenkrantz et al. reported a k coefficient of 0.46 for the determination of PIRADSv2 lesions 3, indicating moderate agreement over random chance [12,13]. As discussed in their study, although this is comparable with other cancer reporting systems including BI-RADS in breast cancer studies, this k coefficient indicates that considerable inter-reader variation still exists. In addition, even after a 2-week training session, the authors found no improvement in reproducibility, which they hypothesised may foretell a potential limit to the degree of achievable reproducibility. In summary, although MRI-targeted biopsy improves the detection of clinically significant disease, it does not yet obviate the need for systematic biopsy. Data from Zhou [14] have indicated that the use of a standard device-guided templating system may further improve the rate of detection of csCaP over current user-guided systematic biopsy. As the development of novel methods for obtaining biopsies and the determination of an optimal biopsy protocol are both still underway, there still remains a role for the combined use of systematic biopsy.
Conflict of Interest L. Marks is co-founder of Avenda Health Inc., a biomedical device company aiming to treat prostate tumours focally with a laser device.
References [1] Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017;389:815e822. [2] Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. New Engl J Med 2018; 378:1767e1777. [3] Kasivisvanathan V, Stabile A, Neves JB, Giganti F, Valerio M, Shanmugabavan Y, et al. Magnetic resonance imagingtargeted biopsy versus systematic biopsy in the detection of prostate cancer: a systematic review and meta-analysis. Eur Urol 2019;76:284e303. [4] Elkhoury FF, Felker ER, Kwan L, Sisk AE, Delfin M, Natarajan S, et al. Comparison of targeted vs systematic prostate biopsy in men who are biopsy naive: the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study. JAMA Surg 2019;154(9):811e818. [5] Rouviere O, Puech P, Renard-Penna R, Claudon M, Roy C, Mege-Lechevallier F, et al. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol 2019;20:100e109. [6] Kuru TH, Wadhwa K, Chang RT, Echeverria LM, Roethke M, Polson A, et al. Definitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg study group for enhanced prostate diagnostics. BJU Int 2013;112:568e577. [7] Miah S, Hosking-Jervis F, Connor MJ, Eldred-Evans D, Shah TT, Arya M, et al. A multicentre analysis of the detection of clinically significant prostate cancer following transperineal image-fusion targeted and nontargeted systematic prostate biopsy in men at risk. Eur Urol Oncol 2019. https://doi.org/10. 1016/j.euo.2019.03.005. [8] Borkowetz A, Platzek I, Toma M, Laniado M, Baretton G, Froehner M, et al. Comparison of systematic transrectal biopsy to transperineal magnetic resonance imaging/ultrasoundfusion biopsy for the diagnosis of prostate cancer. BJU Int 2015;116:873e879. [9] Tonttila PP, Lantto J, Paakko E, Piippo U, Kauppila S, Lammentausta E, et al. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsynaive men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. Eur Urol 2016; 69:419e425. [10] van der Leest M, Cornel E, Israel B, Hendriks R, Padhani AR, Hoogenboom M, et al. Head-to-head comparison of transrectal ultrasound-guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance-guided biopsy in biopsy-naive men with elevated prostate-specific antigen: a large prospective multicenter clinical study. Eur Urol 2019;75:570e578. [11] Priester A, Natarajan S, Khoshnoodi P, Margolis DJ, Raman SS, Reiter RE, et al. Magnetic resonance imaging underestimation
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011
R.J. Chuang, L.S. Marks / Clinical Oncology xxx (xxxx) xxx of prostate cancer geometry: use of patient specific molds to correlate images with whole mount pathology. J Urol 2017; 197:320e326. [12] Rosenkrantz AB, Ginocchio LA, Cornfeld D, Froemming AT, Gupta RT, Turkbey B, et al. Interobserver reproducibility of the PI-RADS Version 2 Lexicon: a multicenter study of six experienced prostate radiologists. Radiology 2016;280:793e804.
5
[13] McHugh ML. Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 2012;22:276e282. [14] Zhou SR, et al. Prostate cancer detection rate of free-hand versus 3D template mapping biopsy using an MRI/ultrasound fusion device in biopsy-naïve men. J Urol 2019. https://doi. org/10.1097/JU.0000000000000587.
Please cite this article as: Chuang RJ, Marks LS, Targeted and Systematic Biopsy for Diagnosis and Management of Prostate Cancer, Clinical Oncology, https://doi.org/10.1016/j.clon.2019.11.011