Comparison of Real-Time Virtual Sonography Navigation Versus BioJet Navigation on Magnetic Resonance Imaging–Guided Prostate Needle Biopsy: A Single Institutional Analysis

Abstract

Objective:

To analyze the effectiveness and complication rate of MRI–guided prostate needle biopsies by using real-time virtual sonography (RVS) vs BioJet navigation.

Methods:

We retrospectively reviewed 171 patients who underwent an MRI–guided prostate needle biopsy at our institution. Patients whose prostate-specific antigen level was >4.0 ng/mL and who had suspicious prostate cancer (PCa) lesions by multiparametric MRI (mpMRI) underwent 2-core MRI-guided targeted biopsy (TB) and for MRI–guided TB: RVS and BioJet. RVS navigation synchronized mpMRI images with transrectal ultrasound (TRUS) images. BioJet navigation used a software program that merged images from mpMRI and TRUS to produce a composite image. We retrospectively compared the detection rate of PCa and the frequency of severe adverse events (AEs) between these two navigation systems, focusing on patients. In addition, we compared the detection rate of MRI–guided TB cores of two navigation systems regarding anatomical position (transitional zone [TZ] or peripheral zone [PZ]).

Results:

Data from RVS and BioJet biopsy groups were from 65 and 106 patients, respectively. Of these, RVS-TB included 141 cores (PZ: 49 cores, TZ: 92 cores), and BioJet-TB included 276 cores (PZ: 73 cores, TZ: 203 cores). In detecting PCa, by conducting both systematic biopsy and TB, and AEs in patients, a significant difference was not noted between RVS and BioJet navigation systems. In addition, there was no significant difference in the total detection rate for PCa in TB cores between the two methods. However, in the TZ, BioJet navigation showed a significantly higher detection rate of PCa than RVS navigation (35.0% vs 17.4%, p = 0.0023) by analyzing the cores of MRI–guided TB.

Conclusion:

When targeting TZ lesions, BioJet navigation had a greater detection rate for PCa compared with that of RVS navigation.

Introduction

The high incidence of prostate cancer (PCa) in developed countries is a major problem. However, the majority of men diagnosed with PCa will die of other causes, leading to increasing active surveillance based on precise evaluations of PCa risk.^1,2 A prostate needle biopsy is a definitive diagnostic procedure and, together with transrectal ultrasonography (TRUS), has been used for decades by urologists.³ The combination of a directly targeted biopsy (TB) for a visible lesion using TRUS, and a systematic biopsy (SB) is usual in a prostate biopsy. However, methods using TRUS alone do not yield a high detection rate for clinically significant PCa (csPCa).^4,5

The effectiveness of multiparametric MRI (mpMRI) before prostate needle biopsy for detection, evaluation, risk stratification for a staging diagnosis, and estimation during active surveillance has been steadily increasing.^6,7 To improve diagnostic accuracy, MRI guidance to target lesions for prostate biopsy was established in the late 2000s. Nowadays, three techniques for MRI–guided TB exist: (1) direct in-bore MRI–guided biopsy; (2) MRI–TRUS fusion biopsy, including our method using BioJet navigation; and (3) cognitive registration or synchronized image-guided TRUS biopsy, including our method using real-time virtual sonography (RVS) navigation.^8

–12 Recent evidence suggests that TB may be superior to SB even in a primary biopsy setting.^4,6,13,14 An MRI–guided TB appears superior to a standard biopsy using TRUS alone for improving the detection rate of csPCa, or for reducing insignificant PCas.¹⁵ In 2012, the international MRI Working Group released a Prostate Imaging Reporting and Data System (PI–RADS) to standardize reporting and mapping of all prostate lesions.^16,17 Subsequently, several reports have described the effectiveness of various MRI–guided TB methods using TRUS or navigation systems.^4,13,18 An RVS navigation assists TB by showing MRI images synchronized with the TRUS image. A combination of SB and TB of lesions assigned by PI–RADS version 2, a biopsy method using RVS navigation, improved the detection rate of csPCa. For example, a TB using RVS navigation was superior to conventional biopsy for detecting PCa (32% vs 9%).¹⁹ Recently, MRI–guided TB using a BioJet navigation system that induces elastic registration using a needle tracking method with a mechanical position–encoded stepper has been reported.^20,21 BioJet navigation runs a software program that merges images from ultrasound and MRI to produce a new image, and it assists TB by showing a composite image. A TB using a BioJet navigation system was superior to SB in biopsy-naive men.²¹

As described earlier, each navigation system reported a higher detection rate for PCa than TRUS-only biopsy. However, reports directly comparing BioJet and RVS navigation systems are lacking. Therefore, in this study, we compared the diagnostic accuracy and frequency of severe adverse events (AEs) between RVS navigation and BioJet navigation by using accumulated data in a single institution.

Patients and Methods

Patient enrollment

We retrospectively reviewed patients who underwent an MRI–guided prostate needle biopsy at our hospital between April 2017 and July 2019. The criteria for inclusion were as follows: (1) a prostate-specific antigen (PSA) level >4.0 ng/mL; (2) had suspicious cancer lesions by mpMRI; and (3) were required to have an Eastern Cooperative Oncology Group performance status of 1 or lower. At our institution, two methods of MRI–guided prostate needle biopsy exist. The fee for biopsies using a BioJet navigation system is about three times more expensive than one using an RVS navigation system due to the medical care system in Japan. Therefore, all patients were given a detailed explanation of the two methods for MRI–guided prostate needle biopsy by physicians, and they were free to choose the biopsy method according to their financial circumstances. The research was performed with the approval of the institutional review board of Nagoya City University Hospital (approved institutional review board number 46-16-0028).

Protocols for each prostate biopsy method

MpMRI was performed a day before each prostate biopsy according to European guidelines for uro-radiology.^16,22 Images were obtained by using a 3.0 Tesla MRI scanner (Ingenia 3.0T, Philips, Amsterdam, The Netherlands) and included T1-weighted (T1WI), T2-weighted (T2WI), diffusion-weighted, and dynamic contrast-enhanced sequences. All mpMRI images were reviewed by board-certified radiologists with ≥15 years of clinical experience, and who had reviewed more than 700 prostate mpMRIs in our hospital and given pathological feedback. Lesions detected as PCa by mpMRI were evaluated by using PI–RADS version 2. In all cases, biopsies were conducted with each patient in a lithotomy position under spinal anesthesia. During the procedure, a real-time fusion image was continuously available. All biopsies were carried out transperineally, and the process started with a TB; a SB was then performed by using a 12-zone template. An 18-gauge automatic biopsy gun with a 22-mm-sized specimen (Bard Medical, Covington, KY) was used to obtain a biopsy core.

In biopsies using an RVS navigation system, a 12-core SB and a 2-core MRI/TRUS TB (MRI–guided TB) were performed on lesions with a PI–RADS score of 3–5 on MRI. A HI VISION Ascendus ultrasound platform (Hitachi Aloka Medical Ltd., Tokyo, Japan) was used in TRUS. First, MRI Digital Imaging and Communications in Medicine data were directly loaded into the TRUS, and a lesion suspected as PCa on an mpMRI sagittal image was manually contoured as a region of interest (ROI) in an RVS system. After the confirmation of a T2-weighted mpMRI axial image, synchronized images between a real-time sagittal image obtained by TRUS and mpMRI sagittal imaging were constructed by adjusting for the bladder neck and internal orifice that served as landmarks. For synchronization, a magnetic position sensor beside the patient was positioned for recognition of the probe for real-time virtual images. The accuracy of the registration of synchronization was manually confirmed by each operator moving the probe. By precisely adjusting TRUS and mpMRI images on an ultrasonography monitor, a prostate image depicted by TRUS and ROIs derived from images of mpMRI contours were fused in real time with a TRUS image stack during biopsy sessions.

In biopsies using a BioJet navigation system, a 12-core SB and a 2-core TB on lesions with a PI–RADS score of 3–5 on MRI were performed as for the RVS navigation system. For each biopsy, a BioJet software system (D&K Technologies GmbH, Barum, Germany) was used as a workstation, and the HI VISION Ascendus was used as a TRUS. All mpMRI images were captured by the workstation before biopsy. Segmentation that made an outline of the prostate and lesions suspected of clearly being PCa was performed, and an mpMRI three-dimensional (3D) model in each patient was constructed. This procedure contributed to a correction of position aberrations caused by the pressure of the transrectal probe. Next, the mpMRI 3D model and TRUS images were fused by the probe with sensors of position coordinates after insertion of the TRUS probe. If the operators decided a lesion was a suspected PCa on the MRI–TRUS fusion image, template coordinates were shown and a real-time BioJet navigation guided biopsy was performed. All complications were assessed according to the Clavien–Dindo Classification of surgical complications during hospitalization and outpatient visits.

Pathological assessment

Prostate tissues obtained by biopsy were immediately fixed in formalin. Pathologists who were experienced in PCa assessed the tissues and reported the percentage of PCa area and Gleason score for each core according to the 2005 International Society of Urological Pathology Gleason grading consensus.²³ Pathologists were blinded to the methods used in MRI–guided prostate needle biopsies. The definition of csPCa was that which had at least one core with a Gleason score of 3 + 4 or more.²⁰

Statistical analysis

We compared the diagnostic accuracy of PCa between RVS and BioJet biopsies for each patient and for each core. p < 0.05 was considered statistically significant. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). Specifically, it is a modified version of R commander with statistical functions frequently used in biostatistics.²⁴

Results

Patients' characteristics and cancer detection rate between two groups

Table 1 lists the characteristics of 171 patients, with data from 65 and 106 patients who used RVS and BioJet navigation, respectively. Statistical significance was not found between the two groups, including for age, serum PSA levels, volume of prostate, and distribution of PI–RADS category. The detection rate of PCa or csPCa by SB and TB showed no significant difference between RVS and BioJet groups (58.5% vs 61.9%, p = 0.632, 43.1% vs 52.8%, p = 0.208, respectively). As shown in Table 1, severe AEs, (e.g., hematuria or urinary retention) categorized ≥grade 3 in the Clavien–Dindo Classification were not observed in patients in RVS and BioJet navigation groups. Thus, both RVS and BioJet navigation showed similar detection rates of PCa regardless of the biopsy method used.

Table 1.

Patients' Characteristics and Complication Rates Categorized According to the Clavien–Dindo Classification

Characteristics	RVS group (n = 65)		BioJet group (n = 106)		p
Median age, years (range)	70 (53–88)		69 (53–78)		0.052
Median initial serum PSA level, ng/mL	7.4 (3.2–20.9)		7.1 (3.4–37)		0.51
Median prostate volume, mL	34.5 (16.8–165.4)		33.6 (14.8–126.7)		0.806
Median ADC level in MRI	788 (410–1114)		781 (407–1150)		0.959
PI–RADS category, n (%)
3	41 (56.2)		89 (66.9)		0.101
4	29 (39.7)		34 (25.6)
5	3 (4.1)		10 (7.5)
PCa detection, n (%)	38 (58.5)		65 (61.9)		0.632
Clinically significant PCa detection, n (%)	28 (43.1)		56 (52.8)		0.208
Adverse events categorized by Clavien–Dindo classification	No. of patients in all grades, n (%)	No. of patients in grade3–4, n (%)	No. of patients in all grades, n (%)	No. of patients in grade3–4, n (%)	p
Hematuria	24 (36.9)	0 (0)	38 (35.8)	0 (0)	1
Hematospermia	1 (1.5)	0 (0)	1 (0.9)	0 (0)	1
Rectal bleeding	0 (0)	0 (0)	1 (0.9)	0 (0)	1
Low urinary tract symptoms	4 (6.1)	0 (0)	8 (7.5)	0 (0)	1
Pain	3 (4.6)	0 (0)	5 (4.7)	0 (0)	1
Infection	0 (0)	0 (0)	1 (0.9)	0 (0)	1
Urinary retention	4 (6.1)	0 (0)	2 (1.9)	0 (0)	0.359

ADC = apparent diffusion coefficient; PCa = prostate cancer; PI–RADS = Prostate Imaging Reporting and Data System; PSA = prostate-specific antigen; RVS = real-time virtual sonography.

Biopsy core analysis divided into TB and SB

In this study, 417 TB and 2052 SB specimens were used. TB specimens included 141 RVS–TB and 276 BioJet–TB, and SB specimens included 780 RVS–SB and 1272 BioJet–SB. In TB analysis, statistically significant differences in the data were not observed, including in the rate of PCa cores, volume of MRI-positive lesions, and the area occupied by cancer in each core between RVS–TB and BioJet–TB groups (Table 2). In a similar analysis of SB, the rate of PCa cores and those occupied by cancer were not statistically significant between RVS–SB and BioJet–SB groups. The distribution of Gleason scores between RVS and BioJet groups was not significant for TB and SB. Thus, both RVS and BioJet groups showed similar biopsy core characteristics, regardless of the biopsy method used.

Table 2.

Comparison of TB and SB Cores Using Two Navigation Systems

	TB (n = 417)			SB (n = 2052)
	RVS–TB	BioJet–TB	p	RVS–SB	BioJet–SB	p
No. of biopsy cores, n	141	276		780	1272
No. of PCa cores, n (%)	43 (30.5)	105 (38.0)	0.132	91 (11.7)	116 (9.10)	0.069
Average area occupied by cancer in each core, %	15.1	18.2	0.165	3.37	2.81	0.072
Average volume of lesions detected by MRI, cm³	0.68	0.51	0.063	—	—	—
GS, n (%)
No malignancy	98 (69.5)	171 (62.0)		689 (88.3)	1156 (90.9)
3 + 3	15 (10.6)	32 (11.6)		27 (3.5)	41 (3.2)
3 + 4	10 (7.1)	37 (13.4)		27 (3.5)	37 (2.9)
4 + 3	3 (2.1)	18 (6.5)		15 (1.9)	13 (1.0)
3 + 5	2 (1.4)	3 (1.1)		0 (0)	1 (0.1)
4 + 4	11 (7.8)	10 (3.6)		19 (2.4)	9 (0.7)
4 + 5	2 (1.4)	4 (1.4)		3 (0.4)	13 (1.0)
5 + 4	0 (0)	1 (0.35)		0 (0)	2 (0.2)

GS = Gleason score; TB = targeted biopsy; SB = systemic biopsy.

TB biopsy core analysis of PCa detection rate by mpMRI in peripheral or transitional zones according to PI–RADS category

Next, for the assessment of the diagnostic accuracy of PCa detection using RVS–TB and BioJet–TB, an analysis that focused on prostatic area according to PI–RADS score was performed. In an analysis of the peripheral zone (PZ), MRI-positive lesions in the BioJet–TB group were not statistically significant in categories 3, 4, and in total (Table 3). As a result, the distribution of cancer detection rates and total cancer detection rate were similar for RVS–TB and BioJet–TB groups.

Table 3.

Analysis of Both MRI–Guided TB Cores in the Peripheral Zone

PI–RADS	RVS group (n = 49)	BioJet group (n = 73)	p	RVS group (n = 49)		BioJet group (n = 73)		p
PI–RADS	Median volume cm³ (range)	Median volume cm³ (range)	p	MRI-positive lesions n	Cancer detection cores n, (%)	MRI-positive lesions n	Cancer detection cores n, (%)	p
3	0.25 (0.093–0.65)	0.12 (0.044–1.11)	0.40	17	9 (52.9)	43	18 (41.9)	0.57
4	0.34 (0.040–1.45)	0.24 (0.062–0.60)	0.062	28	15 (53.6)	26	17 (65.4)	0.42
5	1.21 (1.16–1.26)	2.55 (1.93–3.20)	0.010	4	3 (75.0)	4	2 (50.0)	1
Total	0.29 (0.040–1.45)	0.17 (0.044–3.17)	0.48	49	27 (55.1)	73	37 (50.7)	0.71

However, in transitional zone (TZ) analysis, the cancer volume of the RVS–TB group was not significantly larger than that of the BioJet–TB group, except for PI–RADS 4. Also, detection rates of PCa increased with increasing PI–RADS categories. In addition, the detection rate for PI–RADS category 3 in the BioJet–TB group and the total detection rate were significantly greater than those in the RVS–TB group (Table 4). For PI–RADS 4, the cancer detection rate for the BioJet–TB group tended to be greater than that for the RVS–TB group, but a significant difference was not found. Thus, cancer volume and cancer detection rates were greater for the BioJet–TB group compared with the RVS–TB group in the TZ.

Table 4.

Analysis of Both MRI–Guided TB Cores in the Transitional Zone

PI–RADS	RVS group (n = 92)	BioJet group (n = 203)	p	RVS group (n = 92)		BioJet group (n = 203)		p
PI–RADS	Median volume cm³ (range)	Median volume cm³ (range)	p	MRI-positive lesions n	Cancer detection cores n, (%)	MRI-positive lesions n	Cancer detection cores n, (%)	p
3	0.30 (0.070–4.71)	0.28 (0.028–4.57)	0.36	61	3 (4.9)	140	29 (20.7)	0.005
4	0.34 (0.24–1.83)	0.28 (0.066–0.96)	0.009	29	11 (37.9)	44	28 (63.6)	0.054
5	8.79 (8.79–8.79)	1.22 (0.34–2.48)	<0.001	2	2 (100)	19	14 (73.7)	1
Total	0.32 (0.070–8.79)	0.29 (0.028–4.57)	0.049	92	16 (17.4)	203	71 (35.0)	0.0023

Discussion

TB detects more csPCa and fewer insignificant PCa compared with SB alone in a repeat biopsy setting.^25,26 Nowadays, as described earlier, three techniques of MRI–guided biopsy for TB exist. However, in 2019, a multicenter randomized controlled trial did not find any significant advantages in csPCa detection rates among these three biopsy techniques.^27,28 Direct, in-bore, MRI–guided biopsy can accurately target MRI-positive lesions but is time-consuming, expensive, and access is limited. For these reasons, other MRI–guided prostate needle biopsy methods are commonly performed. Such biopsy methods consist of mpMRI information previously obtained by using software and real-time TRUS images. In addition, synchronized image–guided biopsy, such as our RVS navigation methods, is less expensive. Therefore, to minimize human error and maximize accuracy, several software-derived devices have been used for MRI–guided biopsy methods. Various methods also exist that differ by image registration (e.g., rigid vs elastic), needle tracking (e.g., electromagnetic vs position-encoded joints vs image-based software), and biopsy route (transperineal vs transrectal).

Previous reports highlight the detection rate of SB and TB with RVS or BioJet navigation as 65.5%–87%^19,29 or 70%–90%,^20,21, respectively. However, a direct comparison of these two methods is lacking. In this study, the detection rates of RVS and BioJet were 58.5% and 61.9%, respectively, showing no significant difference. Patient characteristics and the diagnostic accuracy of PCa and csPCa were also not significantly different. In addition, differences in complication rates between the two methods did not exist. These results suggested that both methods are feasible for prostate biopsies in terms of accuracy and safety. The cancer area in each core was not significantly different between RVS and BioJet biopsies in both TB and SB; however, TB for both biopsies showed a higher rate compared with SB. Therefore, TB was more effective in detecting PCa than SB in both biopsies, as also reported by others.

To assess diagnostic accuracy in detecting PCa by RVS–TB and BioJet–TB, a prostate area according to PI–RADS score was analyzed. For the PZ, a difference in the total PCa detection rate was not observed. However, in the TZ, BioJet–TB was superior to RVS–TB for detecting PCa, especially in PI–RADS 3 lesions. Two reasons may exist for such results. First, with regard to the characteristics of a BioJet biopsy, the targeting of lesions was coordinated by a reference that was registered on software, which may have contributed to more accurate targeting in the TZ compared with in an RVS biopsy.²¹ The fusion system in BioJet navigation is composed of elastic registration, therefore this is expected to be more accurate than rigid image registration, including in RVS navigation. In addition, in BioJet, the 3D location of the TRUS probe is calculated by direct attachment to the mechanical stepper on the basis of elastic registration. However, for registration steps in an RVS biopsy, a lesion suspected as PCa on an mpMRI sagittal image was manually contoured as an ROI in the RVS system. To obtain synchronized images of TRUS and mpMRI, sagittal imaging must be precisely constructed by adjusting for the bladder neck and internal orifice as landmarks. Such procedures may worsen registration and increase gaps in techniques by physicians. Second, a TZ was generally larger than a PZ and may have increased the difficulty of targeting suspected cancer lesions in the former. Both RVS and a BioJet biopsy were feasible methods in TB but differences in the navigation system may have led to slight differences in the PCa detection rate, especially in the TZ. Recently, the utility of active surveillance using mpMRI and MRI–TRUS fusion biopsy has been described.³⁰ By further analysis in the future, the patient who had severe benign hypertrophy could be accurately diagnosed as PCa by using the BioJet navigation. To avoid unnecessary biopsies, each biopsy method for diagnosis and active surveillance or robot-assisted prostatectomy with nerve sparing should be investigated by considering the specific situation of each patient and PCa.

Several limitations existed in this study. First, this study was retrospectively conducted and not randomized with a relatively small sample size. Second, assigning patients to an RVS or BioJet biopsy was not randomized since patients selected their biopsy method; therefore, this may have resulted in selection bias. Third, further consideration should be given to a learning curve for physicians during the protocol. Moreover, pathology results with reference to prostatectomy specimens should be checked. Considering that various prostate biopsy methods were used with mpMRI, a lot of validated information obtained from clinical data must be accumulated. Our findings may contribute to the development of diagnostic procedures and estimations for patients with PCa.

In conclusion, by the direct comparison of two MRI–guided biopsies, we found both to be safe and reasonable for diagnosing PCa. However, when targeting the TZ, a BioJet biopsy was better than an RVS biopsy in terms of having a greater PCa detection rate.

Footnotes

Acknowledgment

The authors express their appreciation to Prof. Shoji (Tokai University Hospital) for supervising BioJet biopsies.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This work was supported by Grant-Aid from the Ministry of Education, Culture, Sports Science and Technology of Japan (grant no. 18K16704) and a Grant-Aid from the Aichi Cancer Research Foundation in 2018.

Abbreviations Used

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