Comparison of Cancer Detection Rates Between TRUS-Guided Biopsy and MRI-Targeted Biopsy According to PSA Level in Biopsy-Naive Patients: A Propensity Score Matching Analysis

Accepted Manuscript Comparison of cancer detection rates between TRUS-guided biopsy and MRItargeted biopsy according to PSA level in biopsy-naïve patients: a propensity-score matching analysis Young Hyo Choi, Min Yong Kang, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Chan Kyo Kim, Byung Kwan Park, Hyun Moo Lee PII:

S1558-7673(18)30362-8

DOI:

10.1016/j.clgc.2018.09.007

Reference:

CLGC 1124

To appear in:

Clinical Genitourinary Cancer

Received Date: 9 May 2018 Revised Date:

26 August 2018

Accepted Date: 7 September 2018

Please cite this article as: Choi YH, Kang MY, Sung HH, Jeon HG, Chang Jeong B, Seo SI, Jeon SS, Kim CK, Park BK, Lee HM, Comparison of cancer detection rates between TRUS-guided biopsy and MRI-targeted biopsy according to PSA level in biopsy-naïve patients: a propensity-score matching analysis, Clinical Genitourinary Cancer (2018), doi: https://doi.org/10.1016/j.clgc.2018.09.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Comparison of cancer detection rates between TRUS-guided biopsy and MRI-targeted biopsy according to PSA level in biopsy-naïve patients: a

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propensity-score matching analysis

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Young Hyo Choi1, Min Yong Kang1, Hyun Hwan Sung1, Hwang Gyun Jeon1, Byong Chang Jeong1, Seong Il Seo1, Seong Soo Jeon1, Chan Kyo Kim2, Byung Kwan Park2 and Hyun Moo

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Lee1

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of

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Medicine, Seoul, Korea

Department of Radiology and Center for Imaging Science, Samsung Medical Center,

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Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence to:

Hyun Moo Lee, M.D., PhD Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: +82-2-3410-3558; Fax: +82-2-3410-3027 E-mail: [email protected]

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Abstract Purpose: To compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-

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guided target prostate biopsy (MRI-TBx) according to prostate specific antigen (PSA) level in biopsy-naïve patients.

Patients and Methods: A retrospective study was conducted in 2,009 biopsy-naïve patients

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with suspected prostate cancer (PSA ≤20 ng/ml). Patients underwent TRUS-Bx (n = 1,786) or MRI-TBx (n = 223) from September 2013 to March 2017 and were stratified by each of

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four PSA cutoffs. MRI-TBx was performed on lesions with PI-RADS scores of 3-5 on mpMRI. Clinically significant prostate cancer (csPC) was defined as Gleason 7 or greater. Propensity-score matching was performed using the prebiopsy variables which included age, PSA, prostate volume, and PSA density.

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Results: Propensity-score matching resulted in 222 patients in each group. There were significant differences between the TRUS-Bx and MRI-TBx groups in the overall detection rates of prostate cancer (41.4% vs. 55.4%, P= 0.003) and csPCa (30.1% vs. 42.8%, P =

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0.005). However, across PSA cutoffs, MRI-TBx detected more prostate cancer than TRUS-

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Bx at PSA levels of 2.5- <4 (29.5% vs. 56.6%, P < 0.001). The csPCa detection rates of TRUS-Bx and MRI-TBx did not differ significantly within the PSA cutoffs. There was a significantly higher detection rate of prostate cancer and csPC in lesions with PI-RADS scores 4 and 5 than in those with a score of 3. Conclusion: Prebiopsy mpMRI and subsequent targeted biopsy had a higher detection rate than the TRUS-Bx in both PCa and csPCa.

ACCEPTED MANUSCRIPT Key words Cancer detection rate; magnetic resonance imaging; prostate biopsy; prostate cancer; prostatic

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specific antigen

Micro-Abstract

To compare cancer detection rates between 12-core TRUS-Bx and MRI-TBx according to PSA levels. Between September 2013 to March 2017, 2,009 biopsy-naïve patients with

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suspected PCa underwent TRUS-Bx or MRI-TBx. Propensity-score matching resulted in 222

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patients in each group. Prebiopsy mpMRI and subsequent targeted biopsy had a higher detection rate than the TRUS-Bx in both PCa and csPCa. However, we could not determine

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the appropriate PSA cutoffs for MRI-TBx in the csPCa detection.

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Introduction To diagnose prostate cancer (PCa), transrectal ultrasound-guided biopsy (TRUS-Bx) is now the standard of care in men with elevated prostatic specific antigen (PSA) levels and/or

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abnormal digital rectal examinations (DRE) 1. However, many patients without PCa undergo unnecessary biopsies, clinically insignificant PCas are often detected, and clinically

significant prostate cancers (csPCa) are sometimes missed 2,3. Furthermore, TRUS-Bx carries

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considerable complications and can cause sepsis 4.

Multiparametric magnetic resonance imaging (mpMRI) has significantly improved the

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diagnostic accuracy for PCa by enabling tumor detection and localization 5-9. Many studies report that MRI-targeted biopsy (MRI-TBx) of suspicious lesions seen by mpMRI enables more precise sampling and increases detection of csPCa while decreasing detection of clinically insignificant PCa 10-13. In men with a previous negative biopsy, MRI-TBx showed

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an improved detection rate of overall PCa in comparison with TRUS-Bx 13,14. However, MRITBx and TRUS-Bx showed similar results for overall PCa detection in men with an initial biopsy 13,14. In recent randomized clinical trials 15,16, overall PCa and csPCa detection was

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similar between the MRI-TBx and TRUS-guided random biopsy in biopsy-naïve patients. In the present study, we aimed to evaluate the diagnostic accuracy of MRI-TBx in

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comparison with TRUS-Bx in biopsy-naïve patients. We also evaluated whether MRI-TBx has increased the detection rate of overall PCa and csPCa compared with TRUS-Bx according to PSA level. To overcome the limitations of retrospective studies, we used propensity-score matching to adjust for prebiopsy variables associated with detection of PCa.

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Materials and Methods Patients Our Institutional Review Board approved this retrospective study, and the requirement for

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informed consent was waived (IRB No. 2018-02-025). Between September 2013 and March 2017, a total of 2,265 biopsy-naïve patients with PSA levels ≥2.5 ng/ml and/or suspicious DRE underwent prostate biopsy at a single tertiary institute. After additional exclusion of 256

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patients with PSA >20 ng/ml, we finally analyzed 2,009 patients. Patients were stratified by each of four PSA cutoffs (PSA <2.5, 2.5- <4, 4- <10, and 10- <20). Clinical and pathological

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information were collected from our prospectively maintained database.

Prostate biopsy was performed with either 12-core TRUS-guided random biopsy (n = 1786) or targeted biopsy using prebiopsy mpMRI examination (n = 223). Two MRI guided biopsy techniques were available: (1) MRI/TRUS fusion target biopsy (n = 83) or (2) cognitive

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registration target biopsy (n = 140).

MRI Protocol and Analysis

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mpMRI was performed with a 3-Tesla magnetic resonance system (Intera Achieva TX,

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Philips Healthcare, Best, the Netherlands) using a phase-array body coil. MRI protocols included T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. After obtaining three-plane localizer images, T2weighted turbo spin-echo images were obtained in the axial, sagittal, and coronal planes. Apparent diffusion coefficient maps were automatically constructed using the manufacturer’s software. Axial dynamic contrast-enhanced imaging was obtained from the prostate apex to base using a 3D fast-field echo sequence. The MR images were independently scored by two radiologists (10 and 15 years of

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to the likelihood of significant prostate cancer being present 17-19.

Prostate Biopsy Procedures

TRUS-Bx (12-core systematic biopsy) was performed under TRUS guidance (IU22,

urologists with different levels of clinical experience.

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Philips Healthcare, Andover, MA, USA) in a standard paired sextant pattern by several

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Two experienced radiologists performed all biopsies in the mpMRI group. One of the two radiologists performed MRI/TRUS fusion target biopsy and the other radiologist performed cognitive target biopsy on lesions with PI-RADS scores of 3-5 on mpMRI, and six to ten cores were obtained for random biopsy in some patients. Subjects with negative MRI findings

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(PI-RADS score 1-2) were not biopsied. Each lesion with a PI-RADS score of 3-5 was biopsied using two or three cores (median 2 cores, range 1-4 cores per patient). A cognitive target biopsy was conducted whenever cancer was suspected from the mpMRI examination,

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and MRI/TRUS fusion target biopsy was performed using the UroNav Fusion Biopsy System (Invivo, Gainesville, FL, USA) and a TRUS probe (Philips Healthcare, Amsterdam, the

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Netherlands) beginning in 2014.

Histopathologic Analysis

An experienced genitourinary pathologist reviewed and described all biopsy cores. The biopsy data included the number of positive biopsy cores, Gleason score, and the maximal percentage of involvement for each positive biopsy core. In addition, high-grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), and inflammation were reported if present. Clinically significant PCa was defined by any Gleason

ACCEPTED MANUSCRIPT pattern of ≥4 20,21. Statistical Analysis Propensity-score matching was performed to reduce selection bias and to adjust for

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significant differences in patient characteristics. The propensity scores were estimated for each patient using multivariate logistic regression analysis including covariates of age, PSA, prostate volume, and PSA density. For the development of propensity-score matched pairs

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without replacement (1:1 match), the local optimal algorithm with the caliper method was used. After matching the propensity-scores of 1786 patients (TRUS-Bx group) and 223

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patients (MRI-TBx group), 222 matched pairs were selected.

Clinical and pathological characteristics were compared by Chi-square test and Wilcoxon rank sum test between the TRUS-Bx and MRI-TBx groups. Differences in PCa detection rates and csPCa detection rates between the two groups were compared using chi-square test

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or Fisher’s exact test as appropriate. Potential predictors of csPCa were included in a multivariate logic regression test if P < 0.1 on univariate analysis. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA) and R 3.4.2 (Vienna,

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Austria; http://www.R-project.org). Statistical significance was considered as P < 0.05.

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Results Prostate biopsies were obtained from 1,786 and 223 patients in the TRUS-Bx and MRITBx groups, respectively. Clinical characteristics of the study cohort are summarized in Table

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1. In the entire cohort, prebiopsy clinical features differed significantly between the two groups. Patients in the MRI-TBx group had a significantly lower prostate volume and higher age and PSA density. PSA levels in patients in the TRUS-Bx group were slightly higher than

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those in MRI-TBx group. Propensity-score matching resulted in a cohort of 222 patients in each group. In the matched cohorts, there were no between-group differences with respect to

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prebiopsy clinical variables, except for the number of biopsy cores and abnormal DRE. Table 2 shows the pathologic results according to the biopsy methods. The two biopsy modalities were compared in terms of the highest Gleason score detected per patient. Of 215 men, 162 (75.3 %) were classified with csPCa (Gleason score 3+4 of greater). In the matched

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cohort, there were significant differences between the TRUS-Bx and MRI-TBx groups in the overall detection rates of PCa (41.4% vs. 55.4%, P= 0.003) and csPCa (30.1% vs. 42.8%, P = 0.005). However, there was no significant difference in the ratio of overall detection of

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csPCa/PCa between the two groups. Although there was a significant difference in the number of positive cores and percentage of maximal involvement of positive core, the

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Gleason score ≥7 was not significantly higher in the MRI-TBx group. In the matched cohort, across PSA cutoffs, MRI-TBx detected more PCa than TRUS-Bx at PSA levels of 2.5- <4 (29.5% vs. 56.6%, P < 0.001; Figure 1B). There was a significant difference between the two groups. The csPCa detection rates of TRUS-Bx and MRI-TBx did not differ significantly within the PSA cutoffs (Figure 2B). In the entire cohort, potential predictive factors of csPCa among any cancer were assessed by univariate analysis. The biopsy method, age, prostate volume, and PSA density were

ACCEPTED MANUSCRIPT significantly associated with csPCa. Multivariate logistic regression model revealed that the MRI-TBx and PSA density remained significant predictors of csPCa after adjusting for potentially confounding variables (Table 3). However, in the matched cohort, there were no

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predictive factors significantly associated with csPCa detection. In the MRI-TBx group, a total of 90 patients did not undergo additional random biopsy after targeted biopsy, and 132 patients underwent the combined (targeted + random) biopsy.

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There was no significant difference between targeted biopsy alone and combined biopsy

groups in the detection rates of PCa (52.2% vs. 57.5%, P = 0.4426) and csPCa (37.8% vs.

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46.2%, P = 0.2634). However, a significant difference was recorded when stratifying the patients in targeted biopsy alone, random biopsy with negative targeted biopsy, and random biopsy with positive targeted biopsy, in terms of the overall detection rates of PCa (52.2% vs. 12.5% vs. 100%, respectively; P <0.001, Table 4) and csPCa (37.8% vs. 1.6% vs. 88.2%,

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respectively; P <0.001, Table 4). In the combined biopsy, only one csPCa (Gleason score 4+4) and eight patients (Gleason score 3+3) were missed with negative targeted biopsy. However, all patients had PCa in random biopsy with positive targeted biopsy.

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The detection rates of PCa and csPCa by targeted biopsy according to PI-RADS scores are reported in Table 5. There was a significantly higher detection rate of PCa and csPCa in

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lesions with PI-RADS scores 4 and 5 than in those with PI-RADS score 3.

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Discussion The use of prebiopsy mpMRI is controversial. In biopsy-proven PCa, MRI is usually performed for staging work-up to make a treatment plan 22. The use of prebiopsy mpMRI is

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not accepted for common practice in many institutes but only for patients with previous negative biopsy and persistently high PSA 23-26. However, mpMRI prior to biopsy may be beneficial in detecting anterior PCa which are likely to be missed in the TRUS-Bx and

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staging patients eligible for active surveillance 27,28. Moreover, prebiopsy mpMRI and

subsequent targeted biopsy may be superior to TRUS-Bx in men without previous prostate

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biopsies. This method may also have potential for reducing the over-diagnosis of men with high risk of insignificant PCa detection when conducting a TRUS-guided random biopsy. In the present study, we aimed to evaluate whether mpMRI-guided target biopsy improves PCa diagnosis among biopsy-naïve men according to PSA level.

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Several prospective studies comparing MRI-TBx and standard biopsy in biopsy-naïve men show that targeted biopsy using mpMRI limited over-detection of insignificant PCa while providing greater detection of csPCa than standard biopsy alone 29-33. Three recently

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published randomized-controlled trials (RCT) have compared a first biopsy based on mpMRI with 12-core standard biopsy alone, producing conflicting results 15,16,34. One RCT included

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175 biopsy-naïve patients suspicious for PCa (PSA increase to 4-20 ng/ml and/or abnormal DRE). In the mpMRI group, 2-core targeted biopsy guided by MRI/TRUS fusion for mpMRI suspicious lesions was followed by 12-core random biopsy. There was no significant difference between the MRI and control groups (random biopsy alone) in the overall detection rate of any PCa (59% vs 54%, P=0.4) or detection rate of csPCa (44% vs 49%, P=0.5) 15. Another RCT included 130 biopsy-naïve patients based on PSA levels <20ng/ml. Patients in the MRI group underwent TRUS-guided random biopsy and cognitive MRI/TRUS fusion target biopsy. The overall PCa and csPCa detection rates were similar between the

ACCEPTED MANUSCRIPT MRI and control groups (64% vs. 57%, P=0.5, and 55% vs. 45%, P=0.8; respectively) 16. However, the most current RCT using MRI/TRUS fusion software-guided target biopsy was recently published 34. In that study, 212 biopsy-naïve men with suspected PCa (PSA≤15

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ng/ml and normal DRE) were randomized into a prebiopsy mpMRI group (arm A) or a control group (arm B). Targeted biopsy was performed in arm A and standard biopsy was performed for patients in arm A with negative mpMRI findings and in arm B. The overall

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detection rates were significantly different for PCa (60.5% vs. 19.2% vs. 29.5%, respectively, P < 0.001) and csPCa (56.8% vs. 3.8% vs. 18.1%, respectively, P < 0.001). Our results

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indicated that prebiopsy mpMRI and subsequent targeted biopsy (MRI/TRUS fusion targeting or cognitive targeting) have improved the value for the diagnosis of overall PCa and csPCa in men without previous biopsy, which is consistent with a previous study 34. This retrospective study used the inclusion criteria similar to the former study 15,16 and compared

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the cancer detection rates of the two groups after prebiopsy variables were matched using propensity-score matching. Our results seemed to confirm the potential role of prebiopsy mpMRI and MRI-TBx in the diagnostic strategy of biopsy-naïve patients with suspected PCa.

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If mpMRI is considered in biopsy-naïve patients, determining which patient populations may be suited to MRI-TBx as an initial diagnostic strategy is important. Patients were

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stratified by each of four PSA cutoffs. We then compared cancer detection rates of overall PCa and csPCa between the two groups across PSA cutoffs. The TRUS-Bx group showed a various PCa detection rate (20.3% vs. 28.8% vs. 31% vs. 53%, respectively) according to the PSA cutoffs (PSA <2.5, 2.5- <4, 4- <10, and 10- <20), whereas the MRI-TBx group showed almost similar diagnostic rates (50% vs. 56.6% vs. 52.8%, 68%, respectively). In the entire cohort, our results demonstrate that use of MRI-TBx in patients with PSA levels <10 ng/ml may be useful for diagnosing any PCa (Figure 1A). In particular, there was a significant difference in the detection rates of csPCa at PSA 2.5- <4 and 4- <10 between the TRUS-Bx

ACCEPTED MANUSCRIPT and the MRI-TBx groups (49.5% vs. 72.1%, P=0.011, and 56.3% vs. 78.6%, P=0.002, respectively; Figure 2A). However, in the matched cohort, there was no significant difference in the detection rates of csPCa within the PSA cutoffs between the two groups. Only in PSA

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levels of 2.5- <4, the overall PCa detection rate was significantly different between the TRUS-Bx and the MRI-TBx groups (29.5% vs. 56.6%, P < 0.001). The PSA cutoffs that we determined may not be universal due to selection bias, suggesting that the role of MRI-TBx

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as an initial diagnostic strategy may remain to be elucidated.

There was no significant difference in cancer detection rates between targeted biopsy alone

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and combined biopsy in the mpMRI group (52.2% vs. 57.5%, P = 0.4426). In the combined biopsy, in case of positive MRI-TBx, PCa was diagnosed in all random biopsies. On the other hand, in MRI-TBx negative cases, eight patients were diagnosed with PCa and only one clinically significant GS 4+4 cancer was missed based on random biopsies. It remains to be

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clarified whether random biopsy can be abandoned when considering suspicious lesions on prebiopsy mpMRI. To our knowledge, MRI-TBx alone is not recommended, but if random biopsy is not required or advanced PCa is reliably identified, MRI-TBx alone can be

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performed 35. Nevertheless, several studies have reported that some high-grade PCa in a small cohort were negative MRI findings 25.

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In our results, MRI-TBx of PI-RADS score 3 lesions had minimal benefit for diagnosing PCa and csPCa. There was a significantly higher detection rate of PCa and csPCa in lesions with PI-RADS scores 4 and 5 than in those with PI-RADS score 3. These data suggest that targeted biopsy of PI-RADS score 3 lesions might not be needed, although some were diagnosed as csPCa. The present study has several limitations to consider. First, this study was retrospectively conducted at a single institution, raising a concern of selection bias. Patients undergoing targeted biopsy for suspicious lesions after prebiopsy mpMRI were compared with patients

ACCEPTED MANUSCRIPT undergoing random biopsy using TRUS. Thus, the cancer detection rate is likely to be higher in targeted biopsy than random biopsy. Second, two radiologists and several urologists with different experience levels performed biopsies, which may have affected results. However,

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this may also make our results more generalizable. Third, our study has a lack of correlation between biopsy findings and suspicious lesions on mpMRI, and possible correlation with pathology and TRUS abnormalities was not assessed. A further limitation is that we did not

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distinguish between MRI/TRUS fusion targeted biopsy and cognitive targeted biopsy in the targeted biopsy group. Several studies comparing MRI/TRUS fusion and cognitive targeted

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biopsy have produced conflicting results. According to recent studies, the overall PCa detection rate is not significantly different between MRI/TRUS fusion biopsy and MRI visually cognitive biopsy 36,37. Finally, the cost effectiveness and potential complications of mpMRI should be evaluated in a future study.

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In conclusion, in biopsy-naïve men with suspected PCa and PSA levels ≤20 ng/ml, MRITBx detected more PCa and csPCa than TRUS-Bx. However, MRI-TBx did not detect more cases to csPCa than TRUS-Bx according to PSA cutoffs. There was significant difference in

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detection rates of overall PCa between the two groups at PSA levels 2.5- <4 ng/ml. Our results supported that prebiopsy mpMRI may be considered in biopsy naïve patients.

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However, in the matched cohort, we could not determine the appropriate PSA cutoffs for MRI-TBx in the csPCa detection.

ACCEPTED MANUSCRIPT Clinical Practice Point To diagnose PCa, TRUS-Bx is currently the standard of care in men with elevated PSA and/or abnormal DRE. mpMRI has significantly improved the diagnostic accuracy for PCa

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by enabling tumor detection and localization. In our study, we aimed to investigate the diagnostic accuracy of MRI-TBx in comparison with TRUS-Bx in biopsy-naïve patients. In addition, we evaluated whether MRI-TBx has increased the detection rate of overall PCa and csPCa compared with TRUS-Bx according to PSA level. . There were significant differences

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between the TRUS-Bx and MRI-TBx groups in the overall detection rates of PCa (41.4% vs.

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55.4%, P= 0.003) and csPCa (30.1% vs. 42.8%, P = 0.005). However, across PSA cutoffs, MRI-TBx detected more PCa than TRUS-Bx at PSA levels of 2.5- <4 (29.5% vs. 56.6%, P < 0.001). The csPCa detection rates of TRUS-Bx and MRI-TBx did not differ significantly within the PSA cutoffs. In biopsy-naïve men with suspected PCa and PSA levels ≤20 ng/ml,

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MRI-TBx detected more PCa and csPCa than TRUS-Bx. However, we could not determine

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the appropriate PSA cutoffs for MRI-TBx in the csPCa detection.

Disclosure

The authors declare no conflict of interest.

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Mendhiratta N, Rosenkrantz AB, Meng X, et al. Magnetic Resonance Imaging-Ultrasound

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Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification. J Urol 2015; 194:1601-6. Mozer P, Roupret M, Le Cossec C, et al. First round of targeted biopsies using magnetic

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resonance imaging/ultrasonography fusion compared with conventional transrectal ultrasonography-guided biopsies for the diagnosis of localised prostate cancer. BJU Int 2015; 115:50-7. 33.

Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound fusionguided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama 2015; 313:390-7.

Porpiglia F, Manfredi M, Mele F, et al. Diagnostic Pathway with Multiparametric Magnetic

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Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naive Patients with Suspected Prostate Cancer. Eur Urol 2017; 72:282-8. 35.

Futterer JJ, Briganti A, De Visschere P, et al. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the

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Literature. Eur Urol 2015; 68:1045-53. Puech P, Rouviere O, Renard-Penna R, et al. Prostate cancer diagnosis: multiparametric

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MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy--prospective multicenter study. Radiology 2013; 268:461-9.

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Wysock JS, Rosenkrantz AB, Huang WC, et al. A prospective, blinded comparison of

magnetic resonance (MR) imaging-ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial. Eur Urol 2014; 66:343-51.

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Figure legend Figure 1 Comparison of cancer detection rate in A, an entire cohort and B, a propensity-score matched cohort by PSA cutoffs for TRUS-Bx versus MRI-TBx.

guided target biopsy; PSA=prostate-specific antigen

RI PT

TRUS-Bx=transrectal ultrasound-guided biopsy; MRI-TBx=magnetic resonance imaging

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Figure 2 Comparison of clinically significant cancer (3+4 or greater) detection rate in A, an entire cohort and B, a propensity-score matched cohort by PSA cutoffs for TRUS-Bx versus

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MRI-TBx.

TRUS-Bx=transrectal ultrasound-guided biopsy; MRI-TBx=magnetic resonance imaging

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guided target biopsy; PSA=prostate-specific antigen

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Table 1 Demographic Characteristics of the Study Population

1786

223

Age, years, median (IQR)

64 (63.6-64.4)

66 (64.3-66.6)

PSA, ng/ml, median (IQR)

4.62 (5.63-5.95)

4.51 (5.19-6.14)

Prostate volume, ml, median (IQR) PSA density, ng/mL2, median (IQR) No. of biopsy cores

38.7 (42.8-44.7) 0.11 (0.14-0.15)

Methods of MRI-TBx, n (%) MRI/TRUS fusion Bx MRI cognitive target Bx

172 (9.6%)

MRI-TBx

222

222

0.035

67 (59-73)

66 (60-71)

0.407

0.367

4.50 (3.38-6.69)

4.50 (3.30-6.67)

0.894

33.3(33.7-37.6)

<0.001

33.5 (25.1-43.8)

33.3 (25-42.9)

0.774

0.13 (0.16-0.20)

0.001

0.13 (0.09-0.20)

0.13 (0.09-0.21)

0.924

9.39±4.12

12.02±0.21

9.38±4.13

10 (8.8-9.9)

12 (12-12)

10 (5-13)

27 (12.1%)

4 (1.8%)

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Abnormal DRE, n (%)

12 (12-12)

TRUS-Bx

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Mean ± SD Median (IQR)

12.02±0.25

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No. of patients

p value

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MRI-TBx

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TRUS-Bx

Propensity-score matched cohort

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Entire cohort

4 (1.8%)

83 (37.2) 140 (62.8)

<0.001

<0.001

p value

<0.001

<0.001

82 (36.9) 140 (63.1)

Abbreviations: TRUS-Bx = transrectal ultrasound-guided biopsy; MRI-TBx = magnetic resonance imaging guided target biopsy; PSA = prostate-specific antigen; DRE = digital rectal examination

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Table 2 Comparison of Pathologic Results and Overall Cancer Detection Rates for the Entire Cohort

1786

223

Overall detection of any PCa, n (%)

522 (29.2)

124 (55.6)

Overall detection of csPCa, n (%)

323 (18.0)

96 (43.0)

61.9

77.4

No. of patients

Ratio of overall detection of csPCa/PCa, % No. of positive cores

p value

TRUS-Bx

MRI-TBx

222

222

<0.001

92 (41.4)

123 (55.4)

0.003

0.001

67 (30.1)

95 (42.8)

0.005

0.001

72.8

77.2

0.457

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MRI-TBx

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TRUS-Bx

Propensity-score matched cohort

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Entire cohort

<0.001

<0.001

Mean ± SD

1.09±2.39

Median (IQR)

0 (0.9-1.2)

2 (2.2-2.9)

1.65±2.78 0 (1.2-2.0)

2.53±2.84 2 (2.1-2.9)

0.001

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Biopsy Gleason score, n (%) 6 7

2.54±2.84

8-10

42.41±30.20

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Maximal involvement of positive core, % Mean ± SD

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199 (38.1) 192 (36.8) 131 (25.1)

28 (22.6) 66 (53.2) 30 (24.2)

60.29±26.41

<0.001

p value

0.748 25 (27.2) 45 (48.9) 22 (23.9)

28 (22.8) 65 (52.8) 30 (24.4)

44.63±32.17

60.04±26.38

<0.001

Abbreviations: TRUS-Bx=transrectal ultrasound-guided biopsy, MRI-TBx=magnetic resonance imaging guided target biopsy, PCa=prostate cancer, csPCa= clinically significant prostate cancer, defined as Gleason 3+4 or greater

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Table 3 Logic Regression Analysis of Factors Predicting Clinically Significant Prostate Cancer among Any Cancer Entire cohort Multivariate

Univariate

p value

OR (95% CI)

p value

OR (95% CI)

p value

OR (95% CI)

p value

2.11 (1.33-3.33)

0.001

2.26 (1.39-3.65)

0.001

1.26 (0.67-2.36)

0.458

1.51 (0.78-2.94)

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(Ref. TRUS-Bx) PSA level Ref.

0.50 (0.18-1.37)

0.181

0.46 (0.16-1.27)

4-10

0.60 (0.22-1.58)

0.303

0.41 (0.14-1.16)

>10-20

2.68 (0.91-7.86)

0.072

2.26 (1.39-3.65)

1.03 (1.01-1.05)

0.004

1.02 (0.99-1.04)

0.98 (0.97-0.99)

0.003

99.08 (22.9-428.4)

<0.001

0.96 (0.88-1.04)

0.375

Age

(Ref. 38 ml) PSA density

(Ref. 10 cores)

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No. of biopsy cores

56.19 (6.93-455.1)

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Prostate volume

Ref.

0.135

0.91 (0.21-3.90)

0.908

0.75 (0.17-3.35)

0.711

0.094

1.20 (0.29-5.00)

0.793

0.81 (0.16-3.98)

0.802

0.744

13.28 (1.19-147.5)

0.035

8.44 (0.66-107.5)

0.100

0.057

1.35 (1.71-2.59)

0.355

0.78 (0.39-1.55)

0.485

2.14 (1.10-4.14)

0.023

1.81 (0.80-4.06)

0.150

1.16 (0.58-2.29)

0.669

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(Ref. 65 yrs)

Ref.

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Ref.

2.5-<4

(Ref. 0.12 ng/mL2)

Multivariate

OR (95% CI)

Biopsy methods

<2.5

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Univariate Parameters

Propensity-score matched cohort

<0.001

Abbreviations: TRUS-Bx=transrectal ultrasound-guided biopsy, PSA=prostate-specific antigen, OR=odds ratio, CI=confidence interval

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Table 4 Comparison of Cancer Detection Rates by Performance of Different Biopsy Approaches in Patients from MRI-TBx Group (n = 222) Combined biopsy*

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TBx alone

p value

RBx with positive TBx

90

64

68

Cancer detection, n (%)

47 (52.2)

8 (12.5)

68 (100)

<0.001

csPCa detection, n (%)

34 (37.8)

1 (1.6)

60 (88.2)

<0.001

88.2

<0.001

Ratio of overall detection of csPCa/PCa, %

72.3

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No. of patients

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RBx with negative TBx

12.5

Abbreviations: csPCa=clinically significant prostate cancer; MRI-TBx=magnetic resonance imaging guided target biopsy; PCa=prostate

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cancer; RBx=random biopsy; TBx=targeted biopsy

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*Combined biopsy = targeted biopsy + random biopsy

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Table 5 Comparison of Cancer Detection Rates by PI-RADS Score in Patients from MRI-TBx (n = 222) PI-RADS score 4

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103

Cancer detection, n (%)

4 (8.3)

55 (53.4)

csPCa detection, n (%)

3 (6.2) 75

71 <0.001

37 (35.9)

55 (77.5)

<0.001

67.3

85.9

0.036

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Ratio of overall detection of csPCa/PCa, %

P value

64 (90.1)

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No. of patients

PI-RADS score 5

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PI-RADS score 3

Abbreviations: MRI-TBx = magnetic resonance imaging guided target biopsy; PCa = prostate cancer; csPCa = clinically significant prostate

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cancer; PI-RADS = Prostate Imaging Reporting and Data System

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