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Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings
Clinical Radiology xxx (xxxx) xxx
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Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings S.Y. Won a, N.H. Cho b, Y.D. Choi c, S.Y. Park a, d, * a Department of Radiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea b Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea c Department of Urology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea d Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
art icl e i nformat ion Article history: Received 19 March 2019 Accepted 1 October 2019
AIM: To evaluate retrospectively the diagnostic usefulness of transrectal ultrasound (TRUS)guided targeted biopsy (TB) for transition zone (TZ) prostate cancer (PCa) in patients with prebiopsy magnetic resonance imaging (MRI). MATERIALS AND METHODS: A consecutive series of 38 patients who underwent TRUSguided TB of TZ lesions were evaluated. TB (mean core number, 2.40.6; range, 2e4) was performed by a single experienced radiologist under cognitive registration between prebiopsy MRI and TRUS. Tumour echogenicity on TRUS and Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring on MRI for targeted TZ lesions were assessed. The interrupted midline sign was defined as a focal lesion traversing the midline of the TZ leading to discontinuity of the midline on both MRI and TRUS. TZ PCa with a Gleason score of 7 or greater was defined as clinically significant PCa (csPCa). RESULTS: The cancer detection rate of TRUS-guided TB for TZ lesions was 78.9% (30/38) for any PCa and 42.1% (16/38) for csPCa. Echogenicity of TZ PCa on TRUS was various and half did not show low echogenicity (low, 50%; intermediate, 26.7%; and high, 23.3%). The interrupted midline sign was identified in 50% (19/38) of patients, which was highly predictive of TZ PCa (94.7%, 18/19). CONCLUSION: TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
* Guarantor and correspondent: S. Y. Park, Department of Radiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea. Tel.: þ82 2 2228 7400; fax: þ82 2 393 3035. E-mail address: [email protected] (S.Y. Park).
Introduction Transition zone (TZ) prostate cancers (PCa) are difficult to detect using ultrasound-guided biopsy alone.1
https://doi.org/10.1016/j.crad.2019.10.001 0009-9260/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Prebiopsy magnetic resonance imaging (MRI) seems to enhance cancer detection in men with clinical suspicion2,3; however, the usefulness of prebiopsy MRI for accurate biopsy of TZ PCa is still uncertain for the following reasons: first, there may be significant overlap in MRI features between benign mimickers and TZ PCa. Jung et al. reported that the positive predictive value of MRI was <70%4; second, there may be significant interreader variability in image interpretation for TZ lesions5; and third, different imaging planes may be related to the limited capability of transrectal ultrasound (TRUS)-guided targeted biopsy (TB). Although real-time fusion or in-bore biopsy has shown promise regarding TB for prostatic lesions,6,7 cognitive registration between MRI and TRUS is simple to apply and still accepted as a technique for TB for MRI-suspected prostatic lesions8e10; however, it is still unclear how TRUS-guided TB under cognitive registration is useful to detect TZ PCa. The purpose of this study was to analyse retrospectively the radiological findings of TZ PCa detected using TRUS-guided TB for patients with prebiopsy MRI, and to assess the diagnostic yield.
Materials and methods
MRI examination Multiparametric prostate MRI including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI) was performed using one of three 3-T MRI machines (Ingenia CX, Philips Medical Systems; Discovery MR750, GE Medical Systems; or MR750w, GE Medical Systems) with a phased-array body coil. Before MRI examination, 20 mg butyl scopolamine (Buscopan, Boehringer Ingelheim, Ingelheim am Rhein, Germany) was injected intramuscularly to suppress bowel peristalsis. MRI protocols of the three pulse sequences are summarised in Table 1. All images covered the whole prostate gland and seminal vesicles. Apparent diffusion coefficient (ADC) maps were obtained from the DWI data using a bfactor of 50 and 1,000 mm2/s using the mono-exponential model. Fat-saturated T1-weighted fast-field-echo images were acquired for DCEI before and after a bolus injection of gadoterate meglumine (Dotarem; Guerbet, Aulnay-SousBois, France) with a rate of 2e3 ml/s using a power injector at a dose of 0.1 mmol/kg body weight, followed by a 20 ml saline flush. Subtraction DCE images were also generated. All the MRI images were archived with PACS (PathSpeed Workstation, GE Healthcare) for the image analysis.
Study patients The institutional review board approved this study, and the requirement for informed consent was waived. Between September 2016 and July 2017, a consecutive series of 118 patients had prebiopsy MRI and subsequent TRUSguided biopsy of the prostate gland (Fig 1). Of the patients, 80 were excluded as follows: (a) TB for an index tumour in the PZ (n¼75); (b) no TB in the prostate gland (n¼2); (c) interval between MRI and biopsy >3 months (n¼2); and (d) biopsy-proven prostate teratoma (n¼1). Therefore, 38 patients (median, 66 years; range, 55e84 years) with prebiopsy prostate MRI and subsequent TRUSguided TB for TZ lesions were included in this study. Seventeen were biopsy-naive patients and 21 had a history of negative prostate biopsy.
Table 1 Prostate magnetic resonance imaging (MRI) protocol. Parameter
T2WI
DWI
DCEI
Orientation Repetition time (ms) Echo time (ms) Section thickness (mm) Field of view (mm) In plane dimension Phase (mm) Frequency (mm) B factor (mm2/s) Temporal resolution (s)
Three planes 4,000e5,000 100e110 3 200
Axial 3,000 90 4 200
Axial 3.3e5.2 1.6e2.3 3 200
0.7 0.4 NA NA
2.5 2.5 0, 50, 1,000 NA
<2 <2 NA 7
Three planes were axial, sagittal, and coronal planes. Two b factors (50 and 1,000 mm2/s) were used for generating ADC maps. T2WI, T2-weighted imaging; DWI, diffusion-weighted imaging; DCEI, dynamic contrast-enhanced imaging.
Figure 1 Flowchart of study patients. Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
S.Y. Won et al. / Clinical Radiology xxx (xxxx) xxx
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Data analysis
TRUS-guided prostate biopsy
A genitourinary radiologist (S.Y.P.) who had 6 years of experience in prostate MRI and biopsy interpreted the MRI and TRUS images. Prebiopsy MRI was reviewed prior to the biopsy. The index lesion size, location (e.g., anterior or posterior), Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score, and presence of the interrupted midline sign were assessed at MRI for each patient. Based on the MRI findings, TRUS images were reviewed under cognitive registration to detect the MRI-detected index lesion. Lesion echogenicity and the interrupted midline sign were analysed using TRUS. Anterior TZ PCa was defined as an index tumour located in the anterior TZ to the prostatic urethra.11,12 The interrupted midline sign was defined as a discontinuity of the prostatic midline by anteriorly located TZ PCa involving the bilateral TZ areas on both MRI and TRUS (Fig 2). Baseline prostate-specific antigen (PSA) was recorded from the electronic medical chart. PSA density was defined by PSA/prostate volume. The prostate volume was measured on axial and sagittal T2WI as follows: (maximum AP diameter)(maximum transverse diameter)(maxi mum longitudinal diameter)0.52.
The interval time between MRI and biopsy was 36 days (range, 12e66). TRUS-guided prostate biopsy comprised TB (median core number, 2; range, 2e4) and subsequent 12-core systemic biopsies. TB was performed with an 18-G biopsy gun (ACECUT, TSK Laboratory, Tochigi, Japan) only for the index lesion for each patient (e.g., the most suspicious lesion in each patient). Cognitive registration between prebiopsy MRI and TRUS (Aixplorer US system, SuperSonic Imagine, Aix-en-Provence, France; EPIQ 5, Philips Medical Systems, Bothell, WA, USA) images was applied for lesion targeting. All biopsies were performed by the same radiologist who interpreted the prebiopsy MRI examinations. An experienced genitourinary pathologist (N.H.C.) who had >15 years of experience analysed the biopsy specimens. In this study, the histopathological results of TB samples were used as the reference standard because the purpose of the study was to evaluate the performance of TRUS-guided TB under cognitive registration with prebiopsy MRI and radiological findings of the targeted TZ lesions. The presence or absence of PCa and Gleason score (GS) were recorded for the targeted samples. Biopsy-proven TZ PCa of GS 7 was defined as clinically significant PCa (csPCa) in this study.
Figure 2 MRI and TRUS images of a 77-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 1.8 cm, in the anterior TZ of the prostate gland (arrows). The lesion was markedly hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal low echoic lesion at the corresponding site (arrows). On both MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of a positive interrupted midline sign. (d) TRUS-guided TB for the lesion under cognitive registration detected PCa of GS 8 (arrowheads). Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Statistical analysis Cancer detection rates of TRUS-guided TB under cognitive registration with prebiopsy MRI were estimated for any PCa or csPCa in TZ, respectively. The ManneWhitney test was used to compare PSA, TB core number, and lesion size between patients with TB-detected PCa and those with no PCa. The ratio of long-to-short axis diameter or PI-RADSv2 category between the two groups with and without the interrupted midline sign by using the ManneWhitney test. PI-RADSv2, lesion echogenicity, and the interrupted midline sign were compared using Fisher’s exact test between the two groups. Spearman’s rank correlation was used to assess the relationship between prebiopsy parameters (i.e., baseline PSA or PSA density, PI-RADSv2 category, lesion size measured by MRI or TRUS, and lesion echogenicity) and tumour GS. Statistical analyses were performed with SPSS (version 23.0; SPSS, Chicago, IL, USA) and MedCalc (version 13.3, MedCalc Software, Mariakerke, Belgium). A p-value of <0.05 was considered statistically significant.
Results
Table 2 Patients characteristics. Parameter
Value
Age (year) 66 (55e84) PSA (ng/dl) 7.3 (3.2e21) Interval between MRI and TB (day) 36 (12e66) Core number of TB (n) 2 (2e4) Cancer detection rate by TB (%) Any PCa 78.9 (30/38) csPCa 42.1 (16/38) GS of TB-detected PCa (%) 6 46.7 (14/30) 7 43.3 (13/30) 8 10 (3/30) Cancer-detection rate according to PI-RADSv2 category (%) Category 3 Any PCa 88.2 (30/34) csPCa 47.1 (16/34) Category 4 Any PCa 100 (20/20) csPCa 55 (11/20) Category 5 Any PCa 100 (13/13) csPCa 53.8 (7/13) Data of age, PSA, interval between MRI and TB, and core number of TB are median (range). PSA, prostate-specific antigen; TB, targeted biopsy; PCa, prostate cancer; csPCa, clinically significant prostate cancer; GS, Gleason score; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
Overall characteristics and cancer detection rate The proportion of biopsy native and repeated biopsy cases were 44.7% (17/38) and 55.3% (21/38), respectively. The median PSA of the study patients was 7.3 ng/dl (range, 3.2e21 ng/dl). Median core number of TB was 2 (range, 2e4). The detection rate of TRUS-guided TB under cognitive registration with prebiopsy MRI for any PCa was 78.9% (30/38; Table 2). The GS of TB-proven TZ PCa was 6 in 14 patients (46.7%), 7 in 13 (43.3%), and 8 in three (10%). Thus, the detection rate of TRUS-guided TB under cognitive registration with prebiopsy MRI for csPCa was 42.1% (16/ 38) in this study. According to PI-RADSv2 categories, the cancer detection rate for csPCa in TZ was 47.1 (16/34) for category 3, 55 (11/20) for category 4, and 53.8 (7/13) for category 5. Therefore, about half of the TB-proven PCa with a PI-RADSv2 category of 4 had a GS of 6.
versus 1.1 cm; p¼0.012; Table 4). The proportion of PIRADSv2 categories was significantly different between the two groups (p<0.05). In the no PCa group, there was no patient with TZ lesions showing a PI-RADSv2 category of 4 or 5. The echogenicity of PCa was low in 15 (50%), intermediate in eight (26.7%), and high in seven (23.3%), which was similar to those of the no cancer group (p>0.05). The interrupted midline sign was more frequently seen in the TB-detected PCa group than in the no cancer group (60% versus 12.5%; p<0.042; Figs 3 and 4). In 30 patients with TB-detected TZ PCa, the interrupted midline sign was present in 18. In 19 TZ lesions with the interrupted midline sign, 18 were revealed as PCa by TB (positive predictive value [PPV] of the interrupted midline sign, 94.7%).
MRI and TRUS features
Table 3 MRI and TRUS findings of 38 index lesions in TZ.
The median size of index TZ lesions was 1.3 cm (range, 0.7e3.2 cm). Thirty-two of 38 TZ lesions were located anteriorly. On MRI, PI-RADSv2 categories consisted of 2 for four patients, 3 for 13, 4 for eight, and 5 for 13 (Table 3). On TRUS images, the index TZ lesions showed low echogenicity for 21, intermediate echogenicity for nine, and high echogenicity for eight patients, compared to that of the adjacent TZ. The interrupted midline sign seen on both MRI and TRUS was detected in half of the patients.
Comparison between TB-detected PCa and no PCa in TZ In comparison to PSA, biopsy, and imaging parameters, lesion size was significantly greater in the TB-detected PCa group than in the no cancer group (median size 1.5 cm
Parameter
Value
Lesion size (cm) Anterior location (%) PI-RADSv2 (%) 2 3 4 5 Lesion echogenicity (%) Low Iso High Interrupted midline sign (%)
1.3 (0.7e3.2) 84.2 (32/38) 10.5 (4/38) 34.2 (13/38) 21 (8/38) 34.2 (13/38) 55.3 (21/38) 23.7 (9/38) 21 (8/38) 50 (19/38)
Data of lesion size is median (range). MRI, magnetic resonance imaging; TRUS, transrectal ultrasound; TZ, transition zone; PCa, prostate cancer; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Table 4 Comparison of clinical and radiological findings between TB-detected PCa and no PCa. Parameter
TB-detected PCa (n¼30)
No PCa (n¼8)
p-Value
PSA (ng/dl) TB core number (n) Lesion size (cm) PI-RADSv2 (%) 3 or greater 4 or greater 5 Lesion echogenicity (%) Low Iso High Interrupted midline sign (%)
7.5 (3.2e21) 2 (2e3) 1.5 (0.7e3.2)
7.3 (3.7e11.5) 2 (2e4) 1.1 (0.7e1.4)
0.566 0.526 0.012
100 (30/30) 70 (21/30) 43.3 (13/30)
50 (4/8) 0 (0/8) 0 (0/8)
0.001 0.001 0.034
50 (15/30) 26.7 (8/30) 23.3 (7/30) 60 (18/30)
75 (6/8) 12.5 (1/8) 12.5 (1/8) 12.5 (1/8)
0.257 0.257 0.660 0.042
Data of PSA, TB core number, and lesion size are median (range). TB, targeted biopsy; PCa, prostate cancer; PSA, prostate-specific antigen; MRI, magnetic resonance imaging; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
There was no difference in the ratio of long-to-short axis diameter between the two TZ groups with and without the interrupted midline sign (median ratio, 1.6 versus 1.4; p¼0.748); however, the PI-RADSv2 category of TZ lesions with the interrupted midline sign was significantly higher than that of lesions without the interrupted midline sign (median PI-RADSv2 category, 5 versus 3; p<0.001). All the lesions showing the
interrupted midline sign were located anteriorly (100%, 18/18).
Relationship between prebiopsy parameters and GS In the present study, PSA (rho¼0.123; p¼0.516), PSA density (rho¼0.199; p¼0.292), PI-RADSv2 category (rho¼0.015; p¼0.933), lesion size measured at MRI (rho¼0.080; p¼0.672)
Figure 3 MRI and TRUS images of a 68-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 1.8 cm, in the anterior TZ of the prostate gland (arrows). The lesion was moderately hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal iso-echoic lesion at the corresponding site (arrows). On both the MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of a positive interrupted midline sign. (d) TRUS-guided TB for the lesion under cognitive registration detected PCa of GS 7 (arrowheads). Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Figure 4 MRI and TRUS images of an 84-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 2.5 cm, in the anterior TZ of the prostate gland (arrows). The lesion was markedly hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal high-echoic lesion at the corresponding site (arrows). On both MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of positive interrupted midline sign. (d) TRUSguided TB for the lesion under cognitive registration detected PCa with a GS of 7 (arrowheads).
or TRUS (rho¼0.111; p¼0.558), and lesion echogenicity (rho¼0.257; p¼0.170) were not significantly correlated with GS of TZ PCa.
Discussion The present study indicates that prebiopsy MRI is useful to TRUS-guided TB for TZ PCa showing PI-RADSv2 category of 3 even under cognitive registration (cancer detection rate, 78.9% for any PCa and 42.1% for csPCa). Knowledge of MRI and sonographic features of TZ PCa, such as lesion echogenicity and the interrupted midline sign, may allow accurate targeting of TZ PCa even under cognitive registration between MRI and TRUS. Researchers have reported that the usefulness of the advanced imaging and biopsy techniques, such as real-time fusion or in-bore biopsy in sampling PCa.6,7 Nevertheless, in-bore biopsy may not be available in every institution. In addition, the data are still conflicting regarding the superiority between cognitive and real-time fusion.3,8,13 Accordingly, in daily practice, TB under cognitive registration still remains a reasonable approach for experienced biopsy operators without advanced equipment.9 Thus, radiological findings of prebiopsy MRI and TRUS addressed in this study may be helpful to recognise TZ PCa. Technically, the image planes are usually different between prebiopsy MRI and TRUS. The sonic direction from the TRUS
probe for obtaining transverse image is usually between the axial and coronal planes of MRI because of the anatomical axis of the rectum.14 Thus, biopsy operators should be aware that MRI-suspected TZ lesions may appear in more apical areas of the peripheral zone (PZ) on the transverse images of TRUS, compared with the axial images of MRI; this discrepancy may be associated with inaccurate targeting of TZ lesions under cognitive registration, especially for the anterior PCa. In a visible case, PCa typically manifests as a focal area of low echogenicity on grey-scale images of TRUS,15 leading to TB when the lesion is also suspected as PCa at the corresponding site of prebiopsy MRI. A previous study reported that high echogenicity of the tumour on TRUS was found in 7.6% of biopsy-proven PCa, regardless of zonal location; however, in the present study, the echogenicity of TZ PCa varies on the TRUS images (low, 50%; intermediate, 26.7%; and high, 23.3%). Therefore, biopsy operators need to know that TB only for the hypoechoic lesions in TZ may have a risk of inaccurate sampling, based on the present data. To the authors’ knowledge, these sonographic features of TZ PCa have not been reported. Anterior PCa accounts for approximately 20% of all PCa.16 Identification of anterior TZ PCa using TRUS is still challenging because of the heterogeneity of the TZ, which may prevent accurate targeting via the TRUS-guided approach. Anterior fibromuscular stroma can sometimes manifest as an anteriorly located symmetric lesion mimicking anterior PCa17; however, MRI is useful to differentiate them.11,18
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
S.Y. Won et al. / Clinical Radiology xxx (xxxx) xxx
Thus, the interrupted midline sign of anterior TZ PCa should be sought during prebiopsy MRI. A recent study demonstrated that the cancer detection rates of PI-RADSv2 category 3, 4, and 5 were 22.2%, 39.1%, and 87.8% for all TZ PCa, and 11.1%, 29.1%, and 77.6% for TZ csPCa, respectively.19 Thus, MRI findings suggesting high PIRADSv2 categories (i.e., category 4 or 5) may still have some limitations in accurately predicting PCa in the TZ, compared with the PZ. Recognising various echogenicity patterns of TZ PCa and the interrupted midline sign, seen in some anterior TZ PCa, may help improve cancer detection. In the present study, none of the prebiopsy clinical or radiological parameters was significantly correlated with GS of TB-proven TZ PCa. Conversely, previous studies have reported that PSA or PSAD, lesion size, or PI-RADSv2 category are associated with tumour aggressiveness.20,21 There may be a possible explanation. Two or three cores of TB may be insufficient to sample the most aggressive region of TZ PCa. In this study, most TZ PCas were located anteriorly where accurate targeting is relatively difficult. In addition, about half of the TB-proven PCa showing PI-RADSv2 category 4 had a GS of 6. Accordingly, increasing the number of biopsy cores (i.e., to three or more) may be required to sample the most aggressive part of TZ PCa under the cognitive registration. In terms of MRI-guided in-bore TB, three or more cores may be acceptable.22 The present study has several limitations. First, TB was performed by a single experienced radiologist. Thus, current data require validation by more operators of multiple institutions. Second, biopsy-naive and repeat-biopsy patients were not analysed separately. The cancer detection rates of prostate biopsy are different according to the history of biopsy.23 Based on current data, further studies are required to assess the usefulness of TRUS-guided TB under cognitive registration with varying biopsy settings. Third, the reference standard of the present study was the histopathological results of the targeted biopsy. It may be that some of the small TZ PCa with a GS of 7 were not detected or were underestimated by imaging or biopsy.24,25 Based on the present initial results, further studies with long-term follow-up or surgical results are required to assess the actual probability of significant TZ PCa. In conclusion, TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration.
Conflict of interest The authors declare no conflict of interest.
References 1. Pelzer AE, Bektic J, Berger AP, et al. Are transition zone biopsies still necessary to improve prostate cancer detection? Results from the tyrol screening project. Eur Urol 2005;48:916e21. discussion 21. 2. Schoots IG, Roobol MJ, Nieboer D, et al. Magnetic resonance imagingtargeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol 2015;68:438e50.
7
3. Puech P, Rouviere O, Renard-Penna R, et al. Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal USMR fusion guidance versus systematic biopsydprospective multicenter study. Radiology 2013;268:461e9. 4. Jung SI, Donati OF, Vargas HA, et al. Transition zone prostate cancer: incremental value of diffusion-weighted endorectal MR imaging in tumour detection and assessment of aggressiveness. Radiology 2013;269:493e503. 5. Rosenkrantz AB, Ginocchio LA, Cornfeld D, et al. Interobserver Reproducibility of the PI-RADS Version 2 lexicon: a multicenter study of six experienced prostate radiologists. Radiology 2016;280:793e804. 6. Valerio M, Donaldson I, Emberton M, et al. Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: a systematic review. Eur Urol 2015;68:8e19. 7. Quentin M, Blondin D, Arsov C, et al. Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naive men with elevated prostate specific antigen. J Urol 2014;192:1374e9. 8. Lee DJ, Recabal P, Sjoberg DD, et al. Comparative effectiveness of targeted prostate biopsy using magnetic resonance imaging ultrasound fusion software and visual targeting: a prospective study. J Urol 2016;196:697e702. 9. Rosenkrantz AB, Verma S, Choyke P, et al. Prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a prior negative biopsy: a consensus statement by AUA and SAR. J Urol 2016;196:1613e8. 10. Tonttila PP, Lantto J, Paakko E, et al. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsy-naive men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. Eur Urol 2016;69:419e25. 11. Shinmoto H, Tamura C, Soga S, et al. Anterior prostate cancer: diagnostic performance of T2-weighted MRI and an apparent diffusion coefficient map. AJR Am J Roentgenol 2015;205:W185e92. 12. Koppie TM, Bianco Jr FJ, Kuroiwa K, et al. The clinical features of anterior prostate cancers. BJU Int 2006;98:1167e71. 13. Cool DW, Zhang X, Romagnoli C, et al. Evaluation of MRI-TRUS fusion versus cognitive registration accuracy for MRI-targeted, TRUS-guided prostate biopsy. AJR Am J Roentgenol 2015;204:83e91. 14. Park BK. Ultrasound-guided genitourinary interventions: principles and techniques. Ultrasonography 2017;36:336e48. 15. Shinohara K, Wheeler TM, Scardino PT. The appearance of prostate cancer on transrectal ultrasonography: correlation of imaging and pathological examinations. J Urol 1989;142:76e82. 16. Bott SR, Young MP, Kellett MJ, et al. Contributors to the UCLHTRPD. Anterior prostate cancer: is it more difficult to diagnose? BJU Int 2002;89:886e9. 17. Kitzing YX, Prando A, Varol C, et al. Benign conditions that mimic prostate carcinoma: MR imaging features with histopathologic correlation. RadioGraphics 2016;36:162e75. 18. Ward E, Baad M, Peng Y, et al. Multi-parametric MR imaging of the anterior fibromuscular stroma and its differentiation from prostate cancer. Abdom Radiol (NY) 2017;42:926e34. 19. Thai JN, Narayanan HA, George AK, et al. Validation of PI-RADS version 2 in transition zone lesions for the detection of prostate cancer. Radiology 2018;288:485e91. 20. Park SY, Shin SJ, Jung DC, et al. PI-RADS version 2: quantitative analysis aids reliable interpretation of diffusion-weighted imaging for prostate cancer. Eur Radiol 2017;27:2776e83. 21. Park BH, Jeon HG, Choo SH, et al. Role of multiparametric 3.0-Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance. BJU Int 2014;113:864e70. 22. Tan N, Lin WC, Khoshnoodi P, et al. In-bore 3-T MR-guided transrectal targeted prostate biopsy: prostate Imaging Reporting and Data System version 2-based diagnostic performance for detection of prostate cancer. Radiology 2017;283:130e9. 23. Yacoub JH, Verma S, Moulton JS, et al. Imaging-guided prostate biopsy: conventional and emerging techniques. RadioGraphics 2012;32:819e37. 24. Seo JW, Shin SJ, Taik Oh Y, et al. PI-RADS Version 2: detection of clinically significant cancer in patients with biopsy Gleason score 6 prostate cancer. AJR Am J Roentgenol 2017;209:W1e9. 25. Borofsky S, George AK, Gaur S, et al. What are we missing? Falsenegative cancers at multiparametric MR imaging of the prostate. Radiology 2018;286:186e95.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings S.Y. Won a, N.H. Cho b, Y.D. Choi c, S.Y. Park a, d, * a Department of Radiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea b Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea c Department of Urology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea d Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
art icl e i nformat ion Article history: Received 19 March 2019 Accepted 1 October 2019
AIM: To evaluate retrospectively the diagnostic usefulness of transrectal ultrasound (TRUS)guided targeted biopsy (TB) for transition zone (TZ) prostate cancer (PCa) in patients with prebiopsy magnetic resonance imaging (MRI). MATERIALS AND METHODS: A consecutive series of 38 patients who underwent TRUSguided TB of TZ lesions were evaluated. TB (mean core number, 2.40.6; range, 2e4) was performed by a single experienced radiologist under cognitive registration between prebiopsy MRI and TRUS. Tumour echogenicity on TRUS and Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring on MRI for targeted TZ lesions were assessed. The interrupted midline sign was defined as a focal lesion traversing the midline of the TZ leading to discontinuity of the midline on both MRI and TRUS. TZ PCa with a Gleason score of 7 or greater was defined as clinically significant PCa (csPCa). RESULTS: The cancer detection rate of TRUS-guided TB for TZ lesions was 78.9% (30/38) for any PCa and 42.1% (16/38) for csPCa. Echogenicity of TZ PCa on TRUS was various and half did not show low echogenicity (low, 50%; intermediate, 26.7%; and high, 23.3%). The interrupted midline sign was identified in 50% (19/38) of patients, which was highly predictive of TZ PCa (94.7%, 18/19). CONCLUSION: TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
* Guarantor and correspondent: S. Y. Park, Department of Radiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea. Tel.: þ82 2 2228 7400; fax: þ82 2 393 3035. E-mail address: [email protected] (S.Y. Park).
Introduction Transition zone (TZ) prostate cancers (PCa) are difficult to detect using ultrasound-guided biopsy alone.1
https://doi.org/10.1016/j.crad.2019.10.001 0009-9260/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Prebiopsy magnetic resonance imaging (MRI) seems to enhance cancer detection in men with clinical suspicion2,3; however, the usefulness of prebiopsy MRI for accurate biopsy of TZ PCa is still uncertain for the following reasons: first, there may be significant overlap in MRI features between benign mimickers and TZ PCa. Jung et al. reported that the positive predictive value of MRI was <70%4; second, there may be significant interreader variability in image interpretation for TZ lesions5; and third, different imaging planes may be related to the limited capability of transrectal ultrasound (TRUS)-guided targeted biopsy (TB). Although real-time fusion or in-bore biopsy has shown promise regarding TB for prostatic lesions,6,7 cognitive registration between MRI and TRUS is simple to apply and still accepted as a technique for TB for MRI-suspected prostatic lesions8e10; however, it is still unclear how TRUS-guided TB under cognitive registration is useful to detect TZ PCa. The purpose of this study was to analyse retrospectively the radiological findings of TZ PCa detected using TRUS-guided TB for patients with prebiopsy MRI, and to assess the diagnostic yield.
Materials and methods
MRI examination Multiparametric prostate MRI including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI) was performed using one of three 3-T MRI machines (Ingenia CX, Philips Medical Systems; Discovery MR750, GE Medical Systems; or MR750w, GE Medical Systems) with a phased-array body coil. Before MRI examination, 20 mg butyl scopolamine (Buscopan, Boehringer Ingelheim, Ingelheim am Rhein, Germany) was injected intramuscularly to suppress bowel peristalsis. MRI protocols of the three pulse sequences are summarised in Table 1. All images covered the whole prostate gland and seminal vesicles. Apparent diffusion coefficient (ADC) maps were obtained from the DWI data using a bfactor of 50 and 1,000 mm2/s using the mono-exponential model. Fat-saturated T1-weighted fast-field-echo images were acquired for DCEI before and after a bolus injection of gadoterate meglumine (Dotarem; Guerbet, Aulnay-SousBois, France) with a rate of 2e3 ml/s using a power injector at a dose of 0.1 mmol/kg body weight, followed by a 20 ml saline flush. Subtraction DCE images were also generated. All the MRI images were archived with PACS (PathSpeed Workstation, GE Healthcare) for the image analysis.
Study patients The institutional review board approved this study, and the requirement for informed consent was waived. Between September 2016 and July 2017, a consecutive series of 118 patients had prebiopsy MRI and subsequent TRUSguided biopsy of the prostate gland (Fig 1). Of the patients, 80 were excluded as follows: (a) TB for an index tumour in the PZ (n¼75); (b) no TB in the prostate gland (n¼2); (c) interval between MRI and biopsy >3 months (n¼2); and (d) biopsy-proven prostate teratoma (n¼1). Therefore, 38 patients (median, 66 years; range, 55e84 years) with prebiopsy prostate MRI and subsequent TRUSguided TB for TZ lesions were included in this study. Seventeen were biopsy-naive patients and 21 had a history of negative prostate biopsy.
Table 1 Prostate magnetic resonance imaging (MRI) protocol. Parameter
T2WI
DWI
DCEI
Orientation Repetition time (ms) Echo time (ms) Section thickness (mm) Field of view (mm) In plane dimension Phase (mm) Frequency (mm) B factor (mm2/s) Temporal resolution (s)
Three planes 4,000e5,000 100e110 3 200
Axial 3,000 90 4 200
Axial 3.3e5.2 1.6e2.3 3 200
0.7 0.4 NA NA
2.5 2.5 0, 50, 1,000 NA
<2 <2 NA 7
Three planes were axial, sagittal, and coronal planes. Two b factors (50 and 1,000 mm2/s) were used for generating ADC maps. T2WI, T2-weighted imaging; DWI, diffusion-weighted imaging; DCEI, dynamic contrast-enhanced imaging.
Figure 1 Flowchart of study patients. Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Data analysis
TRUS-guided prostate biopsy
A genitourinary radiologist (S.Y.P.) who had 6 years of experience in prostate MRI and biopsy interpreted the MRI and TRUS images. Prebiopsy MRI was reviewed prior to the biopsy. The index lesion size, location (e.g., anterior or posterior), Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score, and presence of the interrupted midline sign were assessed at MRI for each patient. Based on the MRI findings, TRUS images were reviewed under cognitive registration to detect the MRI-detected index lesion. Lesion echogenicity and the interrupted midline sign were analysed using TRUS. Anterior TZ PCa was defined as an index tumour located in the anterior TZ to the prostatic urethra.11,12 The interrupted midline sign was defined as a discontinuity of the prostatic midline by anteriorly located TZ PCa involving the bilateral TZ areas on both MRI and TRUS (Fig 2). Baseline prostate-specific antigen (PSA) was recorded from the electronic medical chart. PSA density was defined by PSA/prostate volume. The prostate volume was measured on axial and sagittal T2WI as follows: (maximum AP diameter)(maximum transverse diameter)(maxi mum longitudinal diameter)0.52.
The interval time between MRI and biopsy was 36 days (range, 12e66). TRUS-guided prostate biopsy comprised TB (median core number, 2; range, 2e4) and subsequent 12-core systemic biopsies. TB was performed with an 18-G biopsy gun (ACECUT, TSK Laboratory, Tochigi, Japan) only for the index lesion for each patient (e.g., the most suspicious lesion in each patient). Cognitive registration between prebiopsy MRI and TRUS (Aixplorer US system, SuperSonic Imagine, Aix-en-Provence, France; EPIQ 5, Philips Medical Systems, Bothell, WA, USA) images was applied for lesion targeting. All biopsies were performed by the same radiologist who interpreted the prebiopsy MRI examinations. An experienced genitourinary pathologist (N.H.C.) who had >15 years of experience analysed the biopsy specimens. In this study, the histopathological results of TB samples were used as the reference standard because the purpose of the study was to evaluate the performance of TRUS-guided TB under cognitive registration with prebiopsy MRI and radiological findings of the targeted TZ lesions. The presence or absence of PCa and Gleason score (GS) were recorded for the targeted samples. Biopsy-proven TZ PCa of GS 7 was defined as clinically significant PCa (csPCa) in this study.
Figure 2 MRI and TRUS images of a 77-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 1.8 cm, in the anterior TZ of the prostate gland (arrows). The lesion was markedly hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal low echoic lesion at the corresponding site (arrows). On both MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of a positive interrupted midline sign. (d) TRUS-guided TB for the lesion under cognitive registration detected PCa of GS 8 (arrowheads). Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Statistical analysis Cancer detection rates of TRUS-guided TB under cognitive registration with prebiopsy MRI were estimated for any PCa or csPCa in TZ, respectively. The ManneWhitney test was used to compare PSA, TB core number, and lesion size between patients with TB-detected PCa and those with no PCa. The ratio of long-to-short axis diameter or PI-RADSv2 category between the two groups with and without the interrupted midline sign by using the ManneWhitney test. PI-RADSv2, lesion echogenicity, and the interrupted midline sign were compared using Fisher’s exact test between the two groups. Spearman’s rank correlation was used to assess the relationship between prebiopsy parameters (i.e., baseline PSA or PSA density, PI-RADSv2 category, lesion size measured by MRI or TRUS, and lesion echogenicity) and tumour GS. Statistical analyses were performed with SPSS (version 23.0; SPSS, Chicago, IL, USA) and MedCalc (version 13.3, MedCalc Software, Mariakerke, Belgium). A p-value of <0.05 was considered statistically significant.
Results
Table 2 Patients characteristics. Parameter
Value
Age (year) 66 (55e84) PSA (ng/dl) 7.3 (3.2e21) Interval between MRI and TB (day) 36 (12e66) Core number of TB (n) 2 (2e4) Cancer detection rate by TB (%) Any PCa 78.9 (30/38) csPCa 42.1 (16/38) GS of TB-detected PCa (%) 6 46.7 (14/30) 7 43.3 (13/30) 8 10 (3/30) Cancer-detection rate according to PI-RADSv2 category (%) Category 3 Any PCa 88.2 (30/34) csPCa 47.1 (16/34) Category 4 Any PCa 100 (20/20) csPCa 55 (11/20) Category 5 Any PCa 100 (13/13) csPCa 53.8 (7/13) Data of age, PSA, interval between MRI and TB, and core number of TB are median (range). PSA, prostate-specific antigen; TB, targeted biopsy; PCa, prostate cancer; csPCa, clinically significant prostate cancer; GS, Gleason score; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
Overall characteristics and cancer detection rate The proportion of biopsy native and repeated biopsy cases were 44.7% (17/38) and 55.3% (21/38), respectively. The median PSA of the study patients was 7.3 ng/dl (range, 3.2e21 ng/dl). Median core number of TB was 2 (range, 2e4). The detection rate of TRUS-guided TB under cognitive registration with prebiopsy MRI for any PCa was 78.9% (30/38; Table 2). The GS of TB-proven TZ PCa was 6 in 14 patients (46.7%), 7 in 13 (43.3%), and 8 in three (10%). Thus, the detection rate of TRUS-guided TB under cognitive registration with prebiopsy MRI for csPCa was 42.1% (16/ 38) in this study. According to PI-RADSv2 categories, the cancer detection rate for csPCa in TZ was 47.1 (16/34) for category 3, 55 (11/20) for category 4, and 53.8 (7/13) for category 5. Therefore, about half of the TB-proven PCa with a PI-RADSv2 category of 4 had a GS of 6.
versus 1.1 cm; p¼0.012; Table 4). The proportion of PIRADSv2 categories was significantly different between the two groups (p<0.05). In the no PCa group, there was no patient with TZ lesions showing a PI-RADSv2 category of 4 or 5. The echogenicity of PCa was low in 15 (50%), intermediate in eight (26.7%), and high in seven (23.3%), which was similar to those of the no cancer group (p>0.05). The interrupted midline sign was more frequently seen in the TB-detected PCa group than in the no cancer group (60% versus 12.5%; p<0.042; Figs 3 and 4). In 30 patients with TB-detected TZ PCa, the interrupted midline sign was present in 18. In 19 TZ lesions with the interrupted midline sign, 18 were revealed as PCa by TB (positive predictive value [PPV] of the interrupted midline sign, 94.7%).
MRI and TRUS features
Table 3 MRI and TRUS findings of 38 index lesions in TZ.
The median size of index TZ lesions was 1.3 cm (range, 0.7e3.2 cm). Thirty-two of 38 TZ lesions were located anteriorly. On MRI, PI-RADSv2 categories consisted of 2 for four patients, 3 for 13, 4 for eight, and 5 for 13 (Table 3). On TRUS images, the index TZ lesions showed low echogenicity for 21, intermediate echogenicity for nine, and high echogenicity for eight patients, compared to that of the adjacent TZ. The interrupted midline sign seen on both MRI and TRUS was detected in half of the patients.
Comparison between TB-detected PCa and no PCa in TZ In comparison to PSA, biopsy, and imaging parameters, lesion size was significantly greater in the TB-detected PCa group than in the no cancer group (median size 1.5 cm
Parameter
Value
Lesion size (cm) Anterior location (%) PI-RADSv2 (%) 2 3 4 5 Lesion echogenicity (%) Low Iso High Interrupted midline sign (%)
1.3 (0.7e3.2) 84.2 (32/38) 10.5 (4/38) 34.2 (13/38) 21 (8/38) 34.2 (13/38) 55.3 (21/38) 23.7 (9/38) 21 (8/38) 50 (19/38)
Data of lesion size is median (range). MRI, magnetic resonance imaging; TRUS, transrectal ultrasound; TZ, transition zone; PCa, prostate cancer; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Table 4 Comparison of clinical and radiological findings between TB-detected PCa and no PCa. Parameter
TB-detected PCa (n¼30)
No PCa (n¼8)
p-Value
PSA (ng/dl) TB core number (n) Lesion size (cm) PI-RADSv2 (%) 3 or greater 4 or greater 5 Lesion echogenicity (%) Low Iso High Interrupted midline sign (%)
7.5 (3.2e21) 2 (2e3) 1.5 (0.7e3.2)
7.3 (3.7e11.5) 2 (2e4) 1.1 (0.7e1.4)
0.566 0.526 0.012
100 (30/30) 70 (21/30) 43.3 (13/30)
50 (4/8) 0 (0/8) 0 (0/8)
0.001 0.001 0.034
50 (15/30) 26.7 (8/30) 23.3 (7/30) 60 (18/30)
75 (6/8) 12.5 (1/8) 12.5 (1/8) 12.5 (1/8)
0.257 0.257 0.660 0.042
Data of PSA, TB core number, and lesion size are median (range). TB, targeted biopsy; PCa, prostate cancer; PSA, prostate-specific antigen; MRI, magnetic resonance imaging; PI-RADSv2, Prostate Imaging-Reporting and Data System version 2.
There was no difference in the ratio of long-to-short axis diameter between the two TZ groups with and without the interrupted midline sign (median ratio, 1.6 versus 1.4; p¼0.748); however, the PI-RADSv2 category of TZ lesions with the interrupted midline sign was significantly higher than that of lesions without the interrupted midline sign (median PI-RADSv2 category, 5 versus 3; p<0.001). All the lesions showing the
interrupted midline sign were located anteriorly (100%, 18/18).
Relationship between prebiopsy parameters and GS In the present study, PSA (rho¼0.123; p¼0.516), PSA density (rho¼0.199; p¼0.292), PI-RADSv2 category (rho¼0.015; p¼0.933), lesion size measured at MRI (rho¼0.080; p¼0.672)
Figure 3 MRI and TRUS images of a 68-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 1.8 cm, in the anterior TZ of the prostate gland (arrows). The lesion was moderately hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal iso-echoic lesion at the corresponding site (arrows). On both the MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of a positive interrupted midline sign. (d) TRUS-guided TB for the lesion under cognitive registration detected PCa of GS 7 (arrowheads). Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
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Figure 4 MRI and TRUS images of an 84-year-old patient. (a,b) T2WI and ADC map depicted a focal lesion, measuring 2.5 cm, in the anterior TZ of the prostate gland (arrows). The lesion was markedly hypointense on both T2WI and the ADC map, suggestive of PI-RADSv2 category 5. (c) TRUS also demonstrated a focal high-echoic lesion at the corresponding site (arrows). On both MRI and TRUS images, the prostatic midline (red dotted line of aec) was discontinued by the lesion traversing the midline of the TZ, suggestive of positive interrupted midline sign. (d) TRUSguided TB for the lesion under cognitive registration detected PCa with a GS of 7 (arrowheads).
or TRUS (rho¼0.111; p¼0.558), and lesion echogenicity (rho¼0.257; p¼0.170) were not significantly correlated with GS of TZ PCa.
Discussion The present study indicates that prebiopsy MRI is useful to TRUS-guided TB for TZ PCa showing PI-RADSv2 category of 3 even under cognitive registration (cancer detection rate, 78.9% for any PCa and 42.1% for csPCa). Knowledge of MRI and sonographic features of TZ PCa, such as lesion echogenicity and the interrupted midline sign, may allow accurate targeting of TZ PCa even under cognitive registration between MRI and TRUS. Researchers have reported that the usefulness of the advanced imaging and biopsy techniques, such as real-time fusion or in-bore biopsy in sampling PCa.6,7 Nevertheless, in-bore biopsy may not be available in every institution. In addition, the data are still conflicting regarding the superiority between cognitive and real-time fusion.3,8,13 Accordingly, in daily practice, TB under cognitive registration still remains a reasonable approach for experienced biopsy operators without advanced equipment.9 Thus, radiological findings of prebiopsy MRI and TRUS addressed in this study may be helpful to recognise TZ PCa. Technically, the image planes are usually different between prebiopsy MRI and TRUS. The sonic direction from the TRUS
probe for obtaining transverse image is usually between the axial and coronal planes of MRI because of the anatomical axis of the rectum.14 Thus, biopsy operators should be aware that MRI-suspected TZ lesions may appear in more apical areas of the peripheral zone (PZ) on the transverse images of TRUS, compared with the axial images of MRI; this discrepancy may be associated with inaccurate targeting of TZ lesions under cognitive registration, especially for the anterior PCa. In a visible case, PCa typically manifests as a focal area of low echogenicity on grey-scale images of TRUS,15 leading to TB when the lesion is also suspected as PCa at the corresponding site of prebiopsy MRI. A previous study reported that high echogenicity of the tumour on TRUS was found in 7.6% of biopsy-proven PCa, regardless of zonal location; however, in the present study, the echogenicity of TZ PCa varies on the TRUS images (low, 50%; intermediate, 26.7%; and high, 23.3%). Therefore, biopsy operators need to know that TB only for the hypoechoic lesions in TZ may have a risk of inaccurate sampling, based on the present data. To the authors’ knowledge, these sonographic features of TZ PCa have not been reported. Anterior PCa accounts for approximately 20% of all PCa.16 Identification of anterior TZ PCa using TRUS is still challenging because of the heterogeneity of the TZ, which may prevent accurate targeting via the TRUS-guided approach. Anterior fibromuscular stroma can sometimes manifest as an anteriorly located symmetric lesion mimicking anterior PCa17; however, MRI is useful to differentiate them.11,18
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001
S.Y. Won et al. / Clinical Radiology xxx (xxxx) xxx
Thus, the interrupted midline sign of anterior TZ PCa should be sought during prebiopsy MRI. A recent study demonstrated that the cancer detection rates of PI-RADSv2 category 3, 4, and 5 were 22.2%, 39.1%, and 87.8% for all TZ PCa, and 11.1%, 29.1%, and 77.6% for TZ csPCa, respectively.19 Thus, MRI findings suggesting high PIRADSv2 categories (i.e., category 4 or 5) may still have some limitations in accurately predicting PCa in the TZ, compared with the PZ. Recognising various echogenicity patterns of TZ PCa and the interrupted midline sign, seen in some anterior TZ PCa, may help improve cancer detection. In the present study, none of the prebiopsy clinical or radiological parameters was significantly correlated with GS of TB-proven TZ PCa. Conversely, previous studies have reported that PSA or PSAD, lesion size, or PI-RADSv2 category are associated with tumour aggressiveness.20,21 There may be a possible explanation. Two or three cores of TB may be insufficient to sample the most aggressive region of TZ PCa. In this study, most TZ PCas were located anteriorly where accurate targeting is relatively difficult. In addition, about half of the TB-proven PCa showing PI-RADSv2 category 4 had a GS of 6. Accordingly, increasing the number of biopsy cores (i.e., to three or more) may be required to sample the most aggressive part of TZ PCa under the cognitive registration. In terms of MRI-guided in-bore TB, three or more cores may be acceptable.22 The present study has several limitations. First, TB was performed by a single experienced radiologist. Thus, current data require validation by more operators of multiple institutions. Second, biopsy-naive and repeat-biopsy patients were not analysed separately. The cancer detection rates of prostate biopsy are different according to the history of biopsy.23 Based on current data, further studies are required to assess the usefulness of TRUS-guided TB under cognitive registration with varying biopsy settings. Third, the reference standard of the present study was the histopathological results of the targeted biopsy. It may be that some of the small TZ PCa with a GS of 7 were not detected or were underestimated by imaging or biopsy.24,25 Based on the present initial results, further studies with long-term follow-up or surgical results are required to assess the actual probability of significant TZ PCa. In conclusion, TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration.
Conflict of interest The authors declare no conflict of interest.
References 1. Pelzer AE, Bektic J, Berger AP, et al. Are transition zone biopsies still necessary to improve prostate cancer detection? Results from the tyrol screening project. Eur Urol 2005;48:916e21. discussion 21. 2. Schoots IG, Roobol MJ, Nieboer D, et al. Magnetic resonance imagingtargeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol 2015;68:438e50.
7
3. Puech P, Rouviere O, Renard-Penna R, et al. Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal USMR fusion guidance versus systematic biopsydprospective multicenter study. Radiology 2013;268:461e9. 4. Jung SI, Donati OF, Vargas HA, et al. Transition zone prostate cancer: incremental value of diffusion-weighted endorectal MR imaging in tumour detection and assessment of aggressiveness. Radiology 2013;269:493e503. 5. Rosenkrantz AB, Ginocchio LA, Cornfeld D, et al. Interobserver Reproducibility of the PI-RADS Version 2 lexicon: a multicenter study of six experienced prostate radiologists. Radiology 2016;280:793e804. 6. Valerio M, Donaldson I, Emberton M, et al. Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: a systematic review. Eur Urol 2015;68:8e19. 7. Quentin M, Blondin D, Arsov C, et al. Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naive men with elevated prostate specific antigen. J Urol 2014;192:1374e9. 8. Lee DJ, Recabal P, Sjoberg DD, et al. Comparative effectiveness of targeted prostate biopsy using magnetic resonance imaging ultrasound fusion software and visual targeting: a prospective study. J Urol 2016;196:697e702. 9. Rosenkrantz AB, Verma S, Choyke P, et al. Prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a prior negative biopsy: a consensus statement by AUA and SAR. J Urol 2016;196:1613e8. 10. Tonttila PP, Lantto J, Paakko E, et al. Prebiopsy multiparametric magnetic resonance imaging for prostate cancer diagnosis in biopsy-naive men with suspected prostate cancer based on elevated prostate-specific antigen values: results from a randomized prospective blinded controlled trial. Eur Urol 2016;69:419e25. 11. Shinmoto H, Tamura C, Soga S, et al. Anterior prostate cancer: diagnostic performance of T2-weighted MRI and an apparent diffusion coefficient map. AJR Am J Roentgenol 2015;205:W185e92. 12. Koppie TM, Bianco Jr FJ, Kuroiwa K, et al. The clinical features of anterior prostate cancers. BJU Int 2006;98:1167e71. 13. Cool DW, Zhang X, Romagnoli C, et al. Evaluation of MRI-TRUS fusion versus cognitive registration accuracy for MRI-targeted, TRUS-guided prostate biopsy. AJR Am J Roentgenol 2015;204:83e91. 14. Park BK. Ultrasound-guided genitourinary interventions: principles and techniques. Ultrasonography 2017;36:336e48. 15. Shinohara K, Wheeler TM, Scardino PT. The appearance of prostate cancer on transrectal ultrasonography: correlation of imaging and pathological examinations. J Urol 1989;142:76e82. 16. Bott SR, Young MP, Kellett MJ, et al. Contributors to the UCLHTRPD. Anterior prostate cancer: is it more difficult to diagnose? BJU Int 2002;89:886e9. 17. Kitzing YX, Prando A, Varol C, et al. Benign conditions that mimic prostate carcinoma: MR imaging features with histopathologic correlation. RadioGraphics 2016;36:162e75. 18. Ward E, Baad M, Peng Y, et al. Multi-parametric MR imaging of the anterior fibromuscular stroma and its differentiation from prostate cancer. Abdom Radiol (NY) 2017;42:926e34. 19. Thai JN, Narayanan HA, George AK, et al. Validation of PI-RADS version 2 in transition zone lesions for the detection of prostate cancer. Radiology 2018;288:485e91. 20. Park SY, Shin SJ, Jung DC, et al. PI-RADS version 2: quantitative analysis aids reliable interpretation of diffusion-weighted imaging for prostate cancer. Eur Radiol 2017;27:2776e83. 21. Park BH, Jeon HG, Choo SH, et al. Role of multiparametric 3.0-Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance. BJU Int 2014;113:864e70. 22. Tan N, Lin WC, Khoshnoodi P, et al. In-bore 3-T MR-guided transrectal targeted prostate biopsy: prostate Imaging Reporting and Data System version 2-based diagnostic performance for detection of prostate cancer. Radiology 2017;283:130e9. 23. Yacoub JH, Verma S, Moulton JS, et al. Imaging-guided prostate biopsy: conventional and emerging techniques. RadioGraphics 2012;32:819e37. 24. Seo JW, Shin SJ, Taik Oh Y, et al. PI-RADS Version 2: detection of clinically significant cancer in patients with biopsy Gleason score 6 prostate cancer. AJR Am J Roentgenol 2017;209:W1e9. 25. Borofsky S, George AK, Gaur S, et al. What are we missing? Falsenegative cancers at multiparametric MR imaging of the prostate. Radiology 2018;286:186e95.
Please cite this article as: Won SY et al., Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.10.001