- Email: [email protected]
Central zone lesions on magnetic resonance imaging: Should we be concerned?
Urologic Oncology: Seminars and Original Investigations ] (2016) ∎∎∎–∎∎∎
Original article
Central zone lesions on magnetic resonance imaging: Should we be concerned? Wei Phin Tan, M.D.a,*, Andrew Mazzone, B.S.a, Stephanie Shors, M.D., M.S.b, Nency Antoine, R.D.M.S.a, Shahid Ekbal, M.D.a, Narendra Khare, M.D.a, Charles McKiel, M.D.a, Dennis Pessis, M.D.a, Leslie Deane, M.B.B.S., F.R.C.S.C., F.A.C.S.a a b
Department of Urology, Rush University Medical Center, Chicago, IL Department of Radiology, Rush University Medical Center, Chicago, IL
Received 20 June 2016; received in revised form 4 August 2016; accepted 11 August 2016
Abstract Introduction and objective: The Prostate Imaging Reporting and Data System (PI-RADS) score was developed to evaluate lesions in the peripheral and transition zone on multiparametric magnetic resonance imaging (mpMRI) of the prostate. We aim to determine if the PIRADS scoring system can be used to evaluate central zone lesions on mpMRI. Materials and methods: A retrospective review of 73 patients who underwent mpMRI/ultrasound (US) fusion-guided biopsy of 143 suspicious lesions between February 2014 and October 2015 was performed. All patients underwent a 3 T mpMRI. Indications for mpMRI included an abnormal digital rectal examination, PSA velocity 4 0.75 ng/dl/y, and patients on active surveillance. The mpMRI sequence involved T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement. Using 3-dimensional model software (Invivo Corporation, Gainesville, FL, USA), a minimum of 3 magnetic resonance imaging (MRI)/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of PI-RADS score, using local anesthesia in an outpatient clinic setting. Results: A total of 73 patients underwent MRI/US fusion-guided biopsy of 85 peripheral zone lesions, 31 transitional zone lesions, and 27 central zone lesions. Only 2 (7%) of central zone lesions were positive for prostate cancer. Both patients had lesions which were graded as PI-RADS 3. Both the patients had multifocal lesions that encompassed Z50% of the central and transition zones on the sagittal view MRI images. Both patients previously had transrectal US-guided biopsy of the prostate which was negative for cancer. Both patients underwent a robotic-assisted laparoscopic prostatectomy, each revealing high-grade cancer. Conclusions: Lesions involving only the central gland/zone seen on MRI are less concerning for malignancy and should not be given equal weight as peripheral zone lesions. In this series, no lesions involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MRI/US fusion-guided biopsy. Consideration of a modified PI-RADS scoring system should be given to help identify central zone lesions with malignant potential. r 2016 Elsevier Inc. All rights reserved.
Keywords: Multiparametric magnetic resonance imaging; Prostate cancer; PSA; Central zone lesion; MRI/US biopsy
1. Introduction The prostate is divided into 3 general anatomic zones: peripheral zone, transition zone, and central zone. Prostate cancer most commonly originates from the peripheral zone [1]. Sextant biopsy with the aid of a transrectal ultrasound Corresponding author. Tel.: þ1-312-942-9220; fax: þ1-312-942-4005. E-mail address: [email protected] (W.P. Tan). *
http://dx.doi.org/10.1016/j.urolonc.2016.08.006 1078-1439/r 2016 Elsevier Inc. All rights reserved.
(US) continues to be performed up to this day since it was described in 1989 [2]. The technique initially described obtaining 6 biopsies from the peripheral zone of the prostate. Since then, it has evolved and currently entails sampling in a more systematic manner, with 10 to 12 cores to achieve higher detection rates [3,4]. Over the ensuing 2.5 decades, magnetic resonance imaging (MRI) of the prostate has been used for noninvasive evaluation of the prostate gland and surrounding
2
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6
Fig. 1. Central zone lesion as seen on T2 MRI sequence. Sagittal view of (A) the prostate, (B) patient 1, and (C) patient 2. AFS ¼ anterior fibromuscular stroma; CZ ¼ central zone; PZ ¼ peripheral zone; TZ ¼ transition zone; US ¼ urethra. Figure 1A reproduced with permission [5].
structures. The initial technique for MRI of the prostate involved T1-weighted and T2-weighted pulsed sequences and was primarily used for locoregional staging in patients with biopsy-proven cancer. Further advances in the technology has led to the development of multiparametric magnetic resonance imaging (mpMRI), which combines T1/T2-weighted images with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences for MR image acquisition [5,6].
The technique allows for identification of any lesion which would then be assigned a grade using the Prostate Imaging Reporting and Data System (PI-RADS) scoring system [7]. With the use of MRI, central zone lesions that were typically missed on a standard 12 core sextant biopsy can now be identified. However, the PI-RADS scoring system was only developed to evaluate peripheral zone and transitional zone lesions [7]. In this study, we aim to determine if the PI-RADS scoring system can be used to evaluate central zone lesions on mpMRI.
Fig. 2. Axial, sagittal, and coronal views of the prostate and the central zone lesion.
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6 Table 1 Characteristics of CG and PZ lesions identified on mpMRI Peripheral zone
Central zone
58 85
20 27
27 20 8 3
7 7 5 1
Age, median (first/third quartile) PSA, median (first/third quartile) Number of patients with previous 12 core biopsy Benign GS 3 þ 3 GS 3 þ 4
65 (59.5/71.5)
63 (60/68)
0.90
7.8 (5.5/11.1)
8.2 (5.1/10.5)
0.89
10 4 3
7 0 0
Active surveillance
7
0
Number of patients Number of lesions Race Caucasian African American Hispanic Others
P value
0.61
3
our institution's protocol. The pathology was reviewed by 2 genitourinary pathologists at our institution. The data were collected and maintained in a Microsoft Excel (Microsoft, Redmond, WA) spreadsheet format. Statistical analyses were performed using Intercooled Stata software, version 14.0 (StataCorp, College Station, TX). Percentages were calculated using denominators that reflect the number of patients with available data for each specific variable. Categorical variables were analyzed using the Chisquared test or logistic regression. Continuous variables were compared using the Mann-Whitney rank sum test. Averages were reported as medians, and statistical significance was accepted at the P o 0.05 level.
0.99
3. Results
0.99
2. Methodology This is an institutional review board approved retrospective review of a prospectively collected database on patients who underwent an mpMRI of the prostate followed by MRI/US fusion biopsy of the prostate at a tertiary referral center between February 2014 and October 2015. Data were reviewed from our hospital's electronic health record (Epic Systems, Madison, WI). All men underwent clinical assessment by an attending urologist. Indications for mpMRI of the prostate were abnormal digital rectal examination, elevated PSA, PSA velocity 4 0.75 ng/dl/y, or patients on active surveillance. mpMRI of the prostate was performed using a Siemens MAGNETOM 3 T machine. The following imaging phases were taken: (1) T2 turbo spin echo sagittal phase Fig. 1; (2) T2 turbo spin echo coronal phase; (3) T2 turbo spin echo axial phase; (4) DWI axial phase; (5) T1 turbo spin echo axial phase; and (6) DCE axial phase. Each MRI scan was reviewed and reported by an attending radiologist. Using 3-dimensional modeling software (Invivo Corporation, Gainesville, FL, USA), MRI/US fusion biopsy of the prostate was performed with an end-fire Philips iU22 sonographic probe and system (Amsterdam, The Netherlands). Prostate biopsy samples were obtained using an 18-gauge Bard Max-Core (Bard Medical Division, Covington, GA) needle biopsy gun. A minimum of 3 MRI/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of the PI-RADS score, using local anesthesia in an outpatient clinic setting Fig. 2. Radical prostatectomy was performed by a single surgeon. Whole mount pathology was not performed. The prostate was serially sectioned from apex to base into multiple levels as per
A total of 73 patients underwent MRI/US fusion-guided biopsy of 143 lesions. Characteristics of peripheral zone and central zone lesions are listed in Table 1. The PI-RADS score and the corresponding histopathology results for both peripheral zone and central zone lesions are listed in Table 2. The PI-RADS score, the MRI characteristics (T2, DWI, and DCE), and the histopathology for each of the 27 patients with central zone lesions are depicted in Table 3. The median follow-up was 150 days (first quartile 88 days and third quartile 242 days). Two patients developed urinary tract infections treated with oral antibiotics as outpatients. Only 2 (7%) central zone lesions were positive for prostate cancer. Both patients had lesions that were graded as PI-RADS 3. Each patient had multifocal lesions that encompassed Z50% of the prostate on sagittal view of the MRI. Each of these patients' central zone lesions were given a score of 4 out of a 5-point scale derived from T1/T2 imaging on mpMRI. Both patients previously had 12 core transrectal US-guided systematic biopsy of the prostate that was negative for malignancy. Both patients underwent a robotic assisted laparoscopic prostatectomy. The pathological features of both patients are described in Table 4. Both patients had multifocal tumor involving both sides of the prostate involving all zones on final pathology. Table 2 PI-RADS scoring system and peripheral/central zone lesions with its corresponding biopsy PI-RADS score
Fusion biopsy Peripheral zone
1 2 3 4 5
Central zone
Benign
GS 4 6
Benign
GS 4 6
5 18 20 6 0
1 4 14 12 5
2 4 9 9 1
0 0 2 0 0
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6
4
Table 3 PI-RADS score of central zone lesions and its correlated biopsy Lesion
PI-RADS
T2
DWI
DCE
Fusion biopsy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
2 3 3 3 4 3 4 3 5 3 3 3 4 1 4 3 5 4 4 3 4 3 3 3 4 3 4
3 2 3 4 2 4 4 4 5 2 4 4 3 2 3 3 4 4 3 4 2 3 4 3 4 4 3
1 4 4 2 4 2 5 4 4 4 1 1 4 1 4 1 4 4 4 1 5 4 4 2 4 1 5
1 1 1 1 5 3 2 1 4 1 2 2 3 1 4 3 5 2 5 1 5 2 1 2 3 2 4
Benign Benign Benign 4þ4 Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign 3þ4 Benign Benign Benign Benign Benign Benign Benign
Other than the 2 patients with central zone lesions who were positive for cancer, no other patients with central zone involvement on mpMRI had central zone biopsies positive for cancer (GS Z 6). The 25 lesions with benign central zone fusion biopsies had no extracapsular involvement seen on mpMRI. In our series of patients with central zone lesions, only the 2 patients with central zone lesions who were positive for malignancy underwent a prostatectomy (Table 4).
4. Discussion Approximately, 1 million men in Europe and in the United States undergo a TRUS biopsy annually [8]. However, the accuracy of this procedure is limited by its random nature, and despite the use of simultaneous US examination to identify the prostate for needle placement, routine targeting of suspicious lesions has not been employed. When compared to the approach used in most other solid organ cancers where the lesion is identified on imaging before obtaining directed biopsies of the suspicious area/areas, this approach of randomly performing biopsies of the prostate leads to a number of problems. Multiple studies regarding how many cores to obtain and where to obtain these cores have been performed but the issue remains a debate among urologists [9]. To this end, clinicians have incorporated mpMRI of the
Table 4 Characteristics of both patients with central zone malignancy
PSA, ng/ml Extracapsular involvement based on MRI PI-RADS score Fusion biopsy (GS) Robotic assisted laparoscopic prostatectomy (GS) Prostate size on pathology, cm3 Prostate weight, g Percentage of prostate with cancer on pathology, % Zones involved (peripheral, transition, and central) Laterality of tumor Extra prostatic invasion Seminal vesicle involvement
Patient 1
Patient 2
20.1 Yes
28.0 No
3 4þ4 4þ4
3 3þ4 4þ4
5.5 4.5 2.5
5.2 4.0 4.1
62 40
45 40
All zones
All zones
Both sides No No
Both sides Yes Yes
GS = Gleason score
prostate to assist in determining the location of lesions suspicious for prostate cancer. Although mpMRI of the prostate may show a lesion, the identification and the histopathological grading of prostate cancer still requires tissue to establish a diagnosis. Owing to poor standardization of prostate MRI, the PIRADS v1 score was designed in 2012 by the European Society of Urogenital Radiology (ESUR) to provide an initial guideline and scoring system for prostate MRI [7]. Since its introduction, the PI-RADS v1 has been validated in multiple clinical scenarios [10,11]. However, because of several limitations, the PI-RADS scoring system was further modified in 2016 to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate mpMRI examination, hence improving detection, localization, characterization, and risk stratification in patients with suspected prostate cancer in treatment naïve prostate glands [5]. The PI-RADS scoring system has been demonstrated in multiple studies to correlate with final pathology from prostatectomy specimens. Rosenkrantz et al. retrospectively reviewed 70 patients who underwent mpMRI using T2, DWI, and DCE phases, and compared the PI-RADS scoring system with Likert scales using radical prostatectomy as the reference standard. This group showed that the PI-RADS scoring system had a higher sensitivity when compared to the Likert scales in detecting tumor with GS ¼ 7 or higher [12]. A recent meta-analysis of 1,785 patients, published in 2015, showed a sensitivity of 0.73 to 0.82 and specificity of 0.75 to 0.82 generated from the pooled data of 14 studies using prostatectomy or biopsy as the reference standard [13]. To our knowledge, there has not been a study in the literature specifically analyzing the efficacy of the PI-RADS scoring system to classify central zone lesions on MRI/USguided fusion biopsy. In the present series, both patients
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6
who were diagnosed with cancer in the central zone following MRI/US-guided biopsy had multifocal lesions involving all three anatomical zones on final pathology. Hence, the central zone lesion may not be the responsible site of origin for the malignant lesion, but rather the tumor may have initially developed from the transition zone or the peripheral zone, and transgressed into the central zone. In this series, the patients with solely a central gland/central zone lesion without overlapping involvement of the peripheral zone on mpMRI did not have prostate cancer detected by MRI/US fusion biopsy. Our series used PI-RADS v1 to classify the lesions on mpMRI as PI-RADS v2 was only released in 2016 [5]. However, the authors feel that this is unlikely to affect the data, as neither version of the PIRADS scoring system elaborates on the classification of central zone lesions. In most instances, careful scrutiny of the T2W images allows the transition zone to be distinguished from the central zone. However, in some patients with age-related expansion of the transition zone by benign prostatic hypertrophy, the adenomatous growth may compress and displace the central zone, rendering it challenging to delineate the border between them. Use of the term “central gland,” which refers to the amalgamation of the transition zone and the central zone, is discouraged in PI-RADS v2, as it does not reflect prostatic zonal anatomy as visualized on imaging or as seen on pathologic sectioning. Of significant concern to our group, is the possibility of falsely negative central zone lesions on mpMRI. In this regard, a large retrospective review of radical prostatectomy specimens performed in Australia found that central zone tumors were significantly more aggressive than peripheral or transition zone cancers with a far greater risk of extracapsular extension, seminal vesicle invasion, and positive surgical margins [14]. These findings were corroborated in a study by Vargas et al. [15], which showed that patients with central zone lesions have a higher PSA, Gleason score, and increased likelihood of extracapsular extension. In the present study, both patients with central zone cancers had elevated PSA levels higher than 20 ng/ml, high-grade prostate cancer, and 1 of the 2 patients had extra prostatic extension of cancer upon final pathological examination of the gland. Furthermore, in the Australian series, patients with central zone lesions after radical prostatectomy also had 2 times the probability of developing biochemical failure compared to those with cancers in other zones [14]. Given the aggressive nature of central zone lesions, we suggest that fusion biopsy be performed on all central zone lesions until further work establishes a more accurate and reliable reporting system for these lesions. We acknowledge that there are some limitations to our study including the limited patient number and three onsite specialist genitourinary radiologists of which the latter may produce some variability in determination of the exact demarcation of the central zone. In addition, MRI/US
5
fusion biopsy is performed by three urologists at our institution, potentially producing technical differences that may further confound the study findings. None of our patients have had whole mount examinations because of institution policy. 5. Conclusions Lesions involving solely the central zone as seen on mpMRI appear to be less concerning for malignancy and these lesions should be reviewed and their malignancy potential weighed differently compared to peripheral and transition zone lesions. In this series, no lesion involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MR/US fusion-guided biopsy. Consideration should be given to adaptation of the PI-RADS scoring system to more reliably identify central zone lesions with increased malignant potential. References [1] McNeal JE, Redwine EA, Freiha FS, Stamey TA. Zonal distribution of prostatic adenocarcinoma. Correlation with histologic pattern and direction of spread. Am J Surg Pathol 1988;12:897–906. [2] Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 1989;142:71–4:[discussion 74–5]. [3] Eskew LA, Bare RL, McCullough DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 1997;157:199–202:[discussion 202-3]. [4] Chang JJ, Shinohara K, Bhargava V, Presti JC Jr. Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection. J Urol 1998;160:2111–4. [5] Weinreb JC, Barentsz JO, Choyke PL, Cornud F, Haider MA, Macura KJ, et al. PI-RADS prostate imaging—reporting and data system: 2015, version 2. Eur Urol 2016;69:16–40. [6] Hegde JV, Mulkern RV, Panych LP, Fennessy FM, Fedorov A, Maier SE, et al. Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer. J Magn Reson Imaging 2013;37:1035–54. [7] Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012;22: 746–57. [8] Loeb S, Vellekoop A, Ahmed HU, Catto J, Emberton M, Nam R, et al. Systematic review of complications of prostate biopsy. Eur Urol 2013;64:876–92. [9] Scattoni V, Maccagnano C, Capitanio U, Gallina A, Briganti A, Montorsi F. Random biopsy: when, how many and where to take the cores? World J Urol 2014;32:859–69. [10] Habchi H, Bratan F, Paye A, Pagnoux G, Sanzalone T, MegeLechevallier F, et al. Value of prostate multiparametric magnetic resonance imaging for predicting biopsy results in first or repeat biopsy. Clin Radiol 2014;69:e120–8. [11] Junker D, Schafer G, Edlinger M, Kremser C, Bektic J, Horninger W, et al. Evaluation of the PI-RADS scoring system for classifying mpMRI findings in men with suspicion of prostate cancer. BioMed Res Int 2013;2013:252939. [12] Rosenkrantz AB, Kim S, Lim RP, Hindman N, Deng FM, Babb JS, et al. Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PIRADS) and Likert scales. Radiology 2013;269:482–92.
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[13] Hamoen EH, de Rooij M, Witjes JA, Barentsz JO, Rovers MM. Use of the Prostate Imaging Reporting and Data System (PI-RADS) for prostate cancer detection with multiparametric magnetic resonance imaging: a diagnostic meta-analysis. Eur Urol 2015;67:1112–21. [14] Cohen RJ, Shannon BA, Phillips M, Moorin RE, Wheeler TM, Garrett KL. Central zone carcinoma of the prostate gland: a distinct
tumor type with poor prognostic features. J Urol 2008;179:1762–7: [discussion 1767]. [15] Vargas HA, Akin O, Franiel T, Goldman DA, Udo K, Touijer KA, et al. Normal central zone of the prostate and central zone involvement by prostate cancer: clinical and MR imaging implications. Radiology 2012;262:894–902.
Original article
Central zone lesions on magnetic resonance imaging: Should we be concerned? Wei Phin Tan, M.D.a,*, Andrew Mazzone, B.S.a, Stephanie Shors, M.D., M.S.b, Nency Antoine, R.D.M.S.a, Shahid Ekbal, M.D.a, Narendra Khare, M.D.a, Charles McKiel, M.D.a, Dennis Pessis, M.D.a, Leslie Deane, M.B.B.S., F.R.C.S.C., F.A.C.S.a a b
Department of Urology, Rush University Medical Center, Chicago, IL Department of Radiology, Rush University Medical Center, Chicago, IL
Received 20 June 2016; received in revised form 4 August 2016; accepted 11 August 2016
Abstract Introduction and objective: The Prostate Imaging Reporting and Data System (PI-RADS) score was developed to evaluate lesions in the peripheral and transition zone on multiparametric magnetic resonance imaging (mpMRI) of the prostate. We aim to determine if the PIRADS scoring system can be used to evaluate central zone lesions on mpMRI. Materials and methods: A retrospective review of 73 patients who underwent mpMRI/ultrasound (US) fusion-guided biopsy of 143 suspicious lesions between February 2014 and October 2015 was performed. All patients underwent a 3 T mpMRI. Indications for mpMRI included an abnormal digital rectal examination, PSA velocity 4 0.75 ng/dl/y, and patients on active surveillance. The mpMRI sequence involved T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement. Using 3-dimensional model software (Invivo Corporation, Gainesville, FL, USA), a minimum of 3 magnetic resonance imaging (MRI)/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of PI-RADS score, using local anesthesia in an outpatient clinic setting. Results: A total of 73 patients underwent MRI/US fusion-guided biopsy of 85 peripheral zone lesions, 31 transitional zone lesions, and 27 central zone lesions. Only 2 (7%) of central zone lesions were positive for prostate cancer. Both patients had lesions which were graded as PI-RADS 3. Both the patients had multifocal lesions that encompassed Z50% of the central and transition zones on the sagittal view MRI images. Both patients previously had transrectal US-guided biopsy of the prostate which was negative for cancer. Both patients underwent a robotic-assisted laparoscopic prostatectomy, each revealing high-grade cancer. Conclusions: Lesions involving only the central gland/zone seen on MRI are less concerning for malignancy and should not be given equal weight as peripheral zone lesions. In this series, no lesions involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MRI/US fusion-guided biopsy. Consideration of a modified PI-RADS scoring system should be given to help identify central zone lesions with malignant potential. r 2016 Elsevier Inc. All rights reserved.
Keywords: Multiparametric magnetic resonance imaging; Prostate cancer; PSA; Central zone lesion; MRI/US biopsy
1. Introduction The prostate is divided into 3 general anatomic zones: peripheral zone, transition zone, and central zone. Prostate cancer most commonly originates from the peripheral zone [1]. Sextant biopsy with the aid of a transrectal ultrasound Corresponding author. Tel.: þ1-312-942-9220; fax: þ1-312-942-4005. E-mail address: [email protected] (W.P. Tan). *
http://dx.doi.org/10.1016/j.urolonc.2016.08.006 1078-1439/r 2016 Elsevier Inc. All rights reserved.
(US) continues to be performed up to this day since it was described in 1989 [2]. The technique initially described obtaining 6 biopsies from the peripheral zone of the prostate. Since then, it has evolved and currently entails sampling in a more systematic manner, with 10 to 12 cores to achieve higher detection rates [3,4]. Over the ensuing 2.5 decades, magnetic resonance imaging (MRI) of the prostate has been used for noninvasive evaluation of the prostate gland and surrounding
2
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6
Fig. 1. Central zone lesion as seen on T2 MRI sequence. Sagittal view of (A) the prostate, (B) patient 1, and (C) patient 2. AFS ¼ anterior fibromuscular stroma; CZ ¼ central zone; PZ ¼ peripheral zone; TZ ¼ transition zone; US ¼ urethra. Figure 1A reproduced with permission [5].
structures. The initial technique for MRI of the prostate involved T1-weighted and T2-weighted pulsed sequences and was primarily used for locoregional staging in patients with biopsy-proven cancer. Further advances in the technology has led to the development of multiparametric magnetic resonance imaging (mpMRI), which combines T1/T2-weighted images with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences for MR image acquisition [5,6].
The technique allows for identification of any lesion which would then be assigned a grade using the Prostate Imaging Reporting and Data System (PI-RADS) scoring system [7]. With the use of MRI, central zone lesions that were typically missed on a standard 12 core sextant biopsy can now be identified. However, the PI-RADS scoring system was only developed to evaluate peripheral zone and transitional zone lesions [7]. In this study, we aim to determine if the PI-RADS scoring system can be used to evaluate central zone lesions on mpMRI.
Fig. 2. Axial, sagittal, and coronal views of the prostate and the central zone lesion.
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6 Table 1 Characteristics of CG and PZ lesions identified on mpMRI Peripheral zone
Central zone
58 85
20 27
27 20 8 3
7 7 5 1
Age, median (first/third quartile) PSA, median (first/third quartile) Number of patients with previous 12 core biopsy Benign GS 3 þ 3 GS 3 þ 4
65 (59.5/71.5)
63 (60/68)
0.90
7.8 (5.5/11.1)
8.2 (5.1/10.5)
0.89
10 4 3
7 0 0
Active surveillance
7
0
Number of patients Number of lesions Race Caucasian African American Hispanic Others
P value
0.61
3
our institution's protocol. The pathology was reviewed by 2 genitourinary pathologists at our institution. The data were collected and maintained in a Microsoft Excel (Microsoft, Redmond, WA) spreadsheet format. Statistical analyses were performed using Intercooled Stata software, version 14.0 (StataCorp, College Station, TX). Percentages were calculated using denominators that reflect the number of patients with available data for each specific variable. Categorical variables were analyzed using the Chisquared test or logistic regression. Continuous variables were compared using the Mann-Whitney rank sum test. Averages were reported as medians, and statistical significance was accepted at the P o 0.05 level.
0.99
3. Results
0.99
2. Methodology This is an institutional review board approved retrospective review of a prospectively collected database on patients who underwent an mpMRI of the prostate followed by MRI/US fusion biopsy of the prostate at a tertiary referral center between February 2014 and October 2015. Data were reviewed from our hospital's electronic health record (Epic Systems, Madison, WI). All men underwent clinical assessment by an attending urologist. Indications for mpMRI of the prostate were abnormal digital rectal examination, elevated PSA, PSA velocity 4 0.75 ng/dl/y, or patients on active surveillance. mpMRI of the prostate was performed using a Siemens MAGNETOM 3 T machine. The following imaging phases were taken: (1) T2 turbo spin echo sagittal phase Fig. 1; (2) T2 turbo spin echo coronal phase; (3) T2 turbo spin echo axial phase; (4) DWI axial phase; (5) T1 turbo spin echo axial phase; and (6) DCE axial phase. Each MRI scan was reviewed and reported by an attending radiologist. Using 3-dimensional modeling software (Invivo Corporation, Gainesville, FL, USA), MRI/US fusion biopsy of the prostate was performed with an end-fire Philips iU22 sonographic probe and system (Amsterdam, The Netherlands). Prostate biopsy samples were obtained using an 18-gauge Bard Max-Core (Bard Medical Division, Covington, GA) needle biopsy gun. A minimum of 3 MRI/US fusion-guided biopsy samples were taken from each prostate lesion seen on mpMRI irrespective of the PI-RADS score, using local anesthesia in an outpatient clinic setting Fig. 2. Radical prostatectomy was performed by a single surgeon. Whole mount pathology was not performed. The prostate was serially sectioned from apex to base into multiple levels as per
A total of 73 patients underwent MRI/US fusion-guided biopsy of 143 lesions. Characteristics of peripheral zone and central zone lesions are listed in Table 1. The PI-RADS score and the corresponding histopathology results for both peripheral zone and central zone lesions are listed in Table 2. The PI-RADS score, the MRI characteristics (T2, DWI, and DCE), and the histopathology for each of the 27 patients with central zone lesions are depicted in Table 3. The median follow-up was 150 days (first quartile 88 days and third quartile 242 days). Two patients developed urinary tract infections treated with oral antibiotics as outpatients. Only 2 (7%) central zone lesions were positive for prostate cancer. Both patients had lesions that were graded as PI-RADS 3. Each patient had multifocal lesions that encompassed Z50% of the prostate on sagittal view of the MRI. Each of these patients' central zone lesions were given a score of 4 out of a 5-point scale derived from T1/T2 imaging on mpMRI. Both patients previously had 12 core transrectal US-guided systematic biopsy of the prostate that was negative for malignancy. Both patients underwent a robotic assisted laparoscopic prostatectomy. The pathological features of both patients are described in Table 4. Both patients had multifocal tumor involving both sides of the prostate involving all zones on final pathology. Table 2 PI-RADS scoring system and peripheral/central zone lesions with its corresponding biopsy PI-RADS score
Fusion biopsy Peripheral zone
1 2 3 4 5
Central zone
Benign
GS 4 6
Benign
GS 4 6
5 18 20 6 0
1 4 14 12 5
2 4 9 9 1
0 0 2 0 0
W.P. Tan et al. / Urologic Oncology: Seminars and Original Investigations ] (2016) 1–6
4
Table 3 PI-RADS score of central zone lesions and its correlated biopsy Lesion
PI-RADS
T2
DWI
DCE
Fusion biopsy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
2 3 3 3 4 3 4 3 5 3 3 3 4 1 4 3 5 4 4 3 4 3 3 3 4 3 4
3 2 3 4 2 4 4 4 5 2 4 4 3 2 3 3 4 4 3 4 2 3 4 3 4 4 3
1 4 4 2 4 2 5 4 4 4 1 1 4 1 4 1 4 4 4 1 5 4 4 2 4 1 5
1 1 1 1 5 3 2 1 4 1 2 2 3 1 4 3 5 2 5 1 5 2 1 2 3 2 4
Benign Benign Benign 4þ4 Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign 3þ4 Benign Benign Benign Benign Benign Benign Benign
Other than the 2 patients with central zone lesions who were positive for cancer, no other patients with central zone involvement on mpMRI had central zone biopsies positive for cancer (GS Z 6). The 25 lesions with benign central zone fusion biopsies had no extracapsular involvement seen on mpMRI. In our series of patients with central zone lesions, only the 2 patients with central zone lesions who were positive for malignancy underwent a prostatectomy (Table 4).
4. Discussion Approximately, 1 million men in Europe and in the United States undergo a TRUS biopsy annually [8]. However, the accuracy of this procedure is limited by its random nature, and despite the use of simultaneous US examination to identify the prostate for needle placement, routine targeting of suspicious lesions has not been employed. When compared to the approach used in most other solid organ cancers where the lesion is identified on imaging before obtaining directed biopsies of the suspicious area/areas, this approach of randomly performing biopsies of the prostate leads to a number of problems. Multiple studies regarding how many cores to obtain and where to obtain these cores have been performed but the issue remains a debate among urologists [9]. To this end, clinicians have incorporated mpMRI of the
Table 4 Characteristics of both patients with central zone malignancy
PSA, ng/ml Extracapsular involvement based on MRI PI-RADS score Fusion biopsy (GS) Robotic assisted laparoscopic prostatectomy (GS) Prostate size on pathology, cm3 Prostate weight, g Percentage of prostate with cancer on pathology, % Zones involved (peripheral, transition, and central) Laterality of tumor Extra prostatic invasion Seminal vesicle involvement
Patient 1
Patient 2
20.1 Yes
28.0 No
3 4þ4 4þ4
3 3þ4 4þ4
5.5 4.5 2.5
5.2 4.0 4.1
62 40
45 40
All zones
All zones
Both sides No No
Both sides Yes Yes
GS = Gleason score
prostate to assist in determining the location of lesions suspicious for prostate cancer. Although mpMRI of the prostate may show a lesion, the identification and the histopathological grading of prostate cancer still requires tissue to establish a diagnosis. Owing to poor standardization of prostate MRI, the PIRADS v1 score was designed in 2012 by the European Society of Urogenital Radiology (ESUR) to provide an initial guideline and scoring system for prostate MRI [7]. Since its introduction, the PI-RADS v1 has been validated in multiple clinical scenarios [10,11]. However, because of several limitations, the PI-RADS scoring system was further modified in 2016 to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate mpMRI examination, hence improving detection, localization, characterization, and risk stratification in patients with suspected prostate cancer in treatment naïve prostate glands [5]. The PI-RADS scoring system has been demonstrated in multiple studies to correlate with final pathology from prostatectomy specimens. Rosenkrantz et al. retrospectively reviewed 70 patients who underwent mpMRI using T2, DWI, and DCE phases, and compared the PI-RADS scoring system with Likert scales using radical prostatectomy as the reference standard. This group showed that the PI-RADS scoring system had a higher sensitivity when compared to the Likert scales in detecting tumor with GS ¼ 7 or higher [12]. A recent meta-analysis of 1,785 patients, published in 2015, showed a sensitivity of 0.73 to 0.82 and specificity of 0.75 to 0.82 generated from the pooled data of 14 studies using prostatectomy or biopsy as the reference standard [13]. To our knowledge, there has not been a study in the literature specifically analyzing the efficacy of the PI-RADS scoring system to classify central zone lesions on MRI/USguided fusion biopsy. In the present series, both patients
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who were diagnosed with cancer in the central zone following MRI/US-guided biopsy had multifocal lesions involving all three anatomical zones on final pathology. Hence, the central zone lesion may not be the responsible site of origin for the malignant lesion, but rather the tumor may have initially developed from the transition zone or the peripheral zone, and transgressed into the central zone. In this series, the patients with solely a central gland/central zone lesion without overlapping involvement of the peripheral zone on mpMRI did not have prostate cancer detected by MRI/US fusion biopsy. Our series used PI-RADS v1 to classify the lesions on mpMRI as PI-RADS v2 was only released in 2016 [5]. However, the authors feel that this is unlikely to affect the data, as neither version of the PIRADS scoring system elaborates on the classification of central zone lesions. In most instances, careful scrutiny of the T2W images allows the transition zone to be distinguished from the central zone. However, in some patients with age-related expansion of the transition zone by benign prostatic hypertrophy, the adenomatous growth may compress and displace the central zone, rendering it challenging to delineate the border between them. Use of the term “central gland,” which refers to the amalgamation of the transition zone and the central zone, is discouraged in PI-RADS v2, as it does not reflect prostatic zonal anatomy as visualized on imaging or as seen on pathologic sectioning. Of significant concern to our group, is the possibility of falsely negative central zone lesions on mpMRI. In this regard, a large retrospective review of radical prostatectomy specimens performed in Australia found that central zone tumors were significantly more aggressive than peripheral or transition zone cancers with a far greater risk of extracapsular extension, seminal vesicle invasion, and positive surgical margins [14]. These findings were corroborated in a study by Vargas et al. [15], which showed that patients with central zone lesions have a higher PSA, Gleason score, and increased likelihood of extracapsular extension. In the present study, both patients with central zone cancers had elevated PSA levels higher than 20 ng/ml, high-grade prostate cancer, and 1 of the 2 patients had extra prostatic extension of cancer upon final pathological examination of the gland. Furthermore, in the Australian series, patients with central zone lesions after radical prostatectomy also had 2 times the probability of developing biochemical failure compared to those with cancers in other zones [14]. Given the aggressive nature of central zone lesions, we suggest that fusion biopsy be performed on all central zone lesions until further work establishes a more accurate and reliable reporting system for these lesions. We acknowledge that there are some limitations to our study including the limited patient number and three onsite specialist genitourinary radiologists of which the latter may produce some variability in determination of the exact demarcation of the central zone. In addition, MRI/US
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fusion biopsy is performed by three urologists at our institution, potentially producing technical differences that may further confound the study findings. None of our patients have had whole mount examinations because of institution policy. 5. Conclusions Lesions involving solely the central zone as seen on mpMRI appear to be less concerning for malignancy and these lesions should be reviewed and their malignancy potential weighed differently compared to peripheral and transition zone lesions. In this series, no lesion involving solely the central gland/zone, regardless of PI-RADS score, was positive for malignancy on MR/US fusion-guided biopsy. Consideration should be given to adaptation of the PI-RADS scoring system to more reliably identify central zone lesions with increased malignant potential. References [1] McNeal JE, Redwine EA, Freiha FS, Stamey TA. Zonal distribution of prostatic adenocarcinoma. Correlation with histologic pattern and direction of spread. Am J Surg Pathol 1988;12:897–906. [2] Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 1989;142:71–4:[discussion 74–5]. [3] Eskew LA, Bare RL, McCullough DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 1997;157:199–202:[discussion 202-3]. [4] Chang JJ, Shinohara K, Bhargava V, Presti JC Jr. Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection. J Urol 1998;160:2111–4. [5] Weinreb JC, Barentsz JO, Choyke PL, Cornud F, Haider MA, Macura KJ, et al. PI-RADS prostate imaging—reporting and data system: 2015, version 2. Eur Urol 2016;69:16–40. [6] Hegde JV, Mulkern RV, Panych LP, Fennessy FM, Fedorov A, Maier SE, et al. Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer. J Magn Reson Imaging 2013;37:1035–54. [7] Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012;22: 746–57. [8] Loeb S, Vellekoop A, Ahmed HU, Catto J, Emberton M, Nam R, et al. Systematic review of complications of prostate biopsy. Eur Urol 2013;64:876–92. [9] Scattoni V, Maccagnano C, Capitanio U, Gallina A, Briganti A, Montorsi F. Random biopsy: when, how many and where to take the cores? World J Urol 2014;32:859–69. [10] Habchi H, Bratan F, Paye A, Pagnoux G, Sanzalone T, MegeLechevallier F, et al. Value of prostate multiparametric magnetic resonance imaging for predicting biopsy results in first or repeat biopsy. Clin Radiol 2014;69:e120–8. [11] Junker D, Schafer G, Edlinger M, Kremser C, Bektic J, Horninger W, et al. Evaluation of the PI-RADS scoring system for classifying mpMRI findings in men with suspicion of prostate cancer. BioMed Res Int 2013;2013:252939. [12] Rosenkrantz AB, Kim S, Lim RP, Hindman N, Deng FM, Babb JS, et al. Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PIRADS) and Likert scales. Radiology 2013;269:482–92.
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[13] Hamoen EH, de Rooij M, Witjes JA, Barentsz JO, Rovers MM. Use of the Prostate Imaging Reporting and Data System (PI-RADS) for prostate cancer detection with multiparametric magnetic resonance imaging: a diagnostic meta-analysis. Eur Urol 2015;67:1112–21. [14] Cohen RJ, Shannon BA, Phillips M, Moorin RE, Wheeler TM, Garrett KL. Central zone carcinoma of the prostate gland: a distinct
tumor type with poor prognostic features. J Urol 2008;179:1762–7: [discussion 1767]. [15] Vargas HA, Akin O, Franiel T, Goldman DA, Udo K, Touijer KA, et al. Normal central zone of the prostate and central zone involvement by prostate cancer: clinical and MR imaging implications. Radiology 2012;262:894–902.