Stesura Seveso Archivio Italiano di Urologia e Andrologia 2016; 88, 4296 ORIGINAL PAPER MRI/US fusion prostate biopsy: Our initial experience Vito Lacetera 1, Bernardo Cervelli 1, Antonio Cicetti 1, Giuliana Gabrielloni 1, Michele Montesi 1, Roberto Morcellini 1, Gianni Parri 1, Emilio Recanatini 1, Gianluca Giglioni 2, Andrea Benedetto Galosi 2, Valerio Beatrici 1 1 Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy; 2 Clinica Urologica, Università Politecnica delle Marche, Azienda Ospedaliera Ospedali Runiti, Ancona, Italy. Aim: The objective of this study is to pres- ent our initial experience with magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy using the Koelis Trinity device after the first consecutive 59 patients. Materials and methods: 59 consecutive patients with suspect- ed prostate cancer (PCA) underwent prostate biopsy using Trinity Koelis® (Koelis, Grenoble, France). We divided the patients into 2 groups: patients with a previous negative mapping underwent to a MRI/US fusion re-biopsy (Group A); and biopsy-naïve patients who underwent to a first stereotac- tic 3-D mapping of the prostate (Group B). Group A (22 patients):mean age 64 years (CI 48-73), mean PSA = 7.7 ng/ml (CI 4.2- 9.9); mean prostate volume 55 ml(CI 45-82), Digital Rectal Examination (DRE) positive in 2/22, number of lesions detected by MRI 1.4, mean cores from each MRI target lesion 3 (CI 2-5), mean total cores 15 ( CI 12-19). Group B (37 patients): mean age 66 years (CI 49-77), mean PSA= 4.7 (3.2- 7.9); mean prostate volume 45 ml (33-67), DRE positive in 5/37, mean total cores 14 ( CI 10-16) Results: In Group A 10/22 patients were positive for PCA (overall detection rate of 45.5%): 6 PCA were detected by target biopsy and 4 cancer by random biopsy. Significant prostate cancer (defined as the presence of Gleason pattern 4) was detected in 4/10 patients (Significant PCA detection rate of 40%) and all significant PCA were detected by MRI target biopsy. All PCA detected by random biopsy had Gleason score 3 + 3 = 6. In Group B (biopsy naïve patients) 14/37 patients were positive for PCA (overall detection rate of 37.8%), Significant prostate cancer was detected in 5/14 patients (Significant PCA detection rate of 35,7%). No signifi- cant side effects were recorded. Conclusions: Our overall detection rate was 45.5% and 37.8% in Group A (patients with previous negative biopsy and persistent suspicion of PCA) and in Group B (biopsy naïve patients) respectively; clinical significant PCA detection rate was respectively 40% and 35.7%. These results are simi- lar to current literature and promising for the future. We believe that using platforms of co-registered MRI/US fusion biopsy can potentially improve risk stratification and reduces understaging, undergrading and the need for repeat biopsies in biopsy naïve patients (using a stereotactic first mapping) and in patients with previous negative biopsy and persistent suspicion of PCA ( using a second MRI/US fusion biopsy). KEY WORDS: MRI/US fusion biopsy; Prostate cancer; Prostate biopsy. Submitted 15 November 2016; Accepted 15 December 2016 Summary No conflict of interest declared. INTRODUCTION Transrectal ultrasound-guided random biopsy of the prostate (TRUSB) is still the recommended standard tool for the diagnosis of prostate cancer (PCA) (1). This approach is a blindly sample of the prostate without focus on any specific lesion; there are several limitations in this approach, including failure to detect clinically sig- nificant PCA (due to undersampling); imprecise tumor risk stratification (undergrading) and detection of small, low risk clinically insignificant cancers (overdiagnosis) (2). Undersampling can occur in up to 30% of cases with clinically significant tumors being missed on initial biop- sy; undergrading is exstimated at 46% of cases consid- ered at low risk of progression candidates for active sur- veillance, based on preoperative systematic biopsy, but with an upgraded Gleason score of 7 or greater at final histopathology (3). These diagnostic limitations can lead to repeat biopsies (with related side effects and costs), delayed detection of significant PCA and over treatment. Efforts to overcome sampling error include performing multiple repeat biop- sies and increasing the core number; this resulted in the overdetection of indolent cancers, morbidity attributed to unnecessary biopsies and an increase in cost. Several studies have shown that when serial biopsies are indicated, most cancers that are detected are clinically insignificant and the rate of indolent cancer detection increases (4, 5). Recently, a 3-D stereotactic mapping of the prostate has been proposed in order to have a three- dimensional histological mapping of the gland: this tech- nique can be made by a templated-guided transperineal biopsy that requires anaesthesia (spinal or sedation) and hospitalization, or by a software based transrectal biopsy that records all tracks of the needle on a 3-D map with only a local anaesthesia. This technique should allow not overlapping needle’s tracks with a better 3-D volumetric distribution of the biopsies into the prostatic gland and than a better determination of the extent and location of cancer before definitive therapy (6). Advances in imaging have led to the application of magnetic resonance imag- ing (MRI) for the detection of PCA (7-12) with subse- quent development of software-based co-registration allowing for the integration of MRI with real-time TRUS during prostate biopsy. A number of fusion-guided methods and platforms are now commercially available DOI: 10.4081/aiua.2016.4.296 Presented at 20th National Congress SIEUN, Sciacca 2016 297Archivio Italiano di Urologia e Andrologia 2016; 88, 4 Fusion prostate biopsy with common elements in image and analysis and plan- ning (13-15). We present our initial experience with one of these platforms after the first consecutive 59 patients. MATERIALS AND METHODS Between May 2016 and October 2016, we prospectively evaluated the first consecutive 59 patients who underwent to TRUS biopsy using Trinity Koelis® (Koelis, Grenoble, France) MRI/US Fusion machine. We divided the patients into 2 groups: patients with a previous negative mapping who underwent to a MRI/US fusion re-biopsy (Group A); and biopsy-naïve patients who underwent to a first stereo- tactic 3-D mapping of the prostate (Group B). MRI images were obtained using a 1.5 T scanner with a pelvic phased array coil, each suspicious area was further characterized according to the ESUR PI-RADS v.1 global score (12), MRI were done in different hospital without a central review. Two different urologists made all the biopsies. All biopsy core specimens were examined by 2 urogenital pathologists and graded according to the 2005 International Society of Urological Pathology Modified Gleason Grading System (16). Characteristics of the patients (summarized in Table 1) were in Group A: n° of patients = 22, mean age 64 years (CI 48-73), mean PSA = 7.7 ng/ml (CI 4.2- 9.9), mean prostate volume = 55 ml (CI 45-82), Digital Rectal Examination (DRE) positive ratio = 2/22, number of lesions detected by MRI 1.4 (17 PIRADS 3, 4 PIRADS 4, 1 PIRADS 5), mean cores from each MRI target lesion = 3 (CI 2-5), mean total cores = 15 (CI 12-19). In Group B: n° of patients = 37, mean age 66 years (CI 49-77), mean PSA = 4.7 (3.2- 7.9); mean prostate volume = 45 ml (33-67), DRE positive ratio = 5/37, mean total cores = 14 (CI 10-16). We standardized our MRI/US fusion biopsy technique using Koelis Trinity in 5 steps: First step: MRI T2 and/or DWI images are loaded into the Trinity, we manually border the prostate signing the apex, the base the mid gland and additional landmarks of the prostate obtaining a 3-D MRI volume; than we tar- get the suspected areas described in the MRI report in a semiautomatic process. This step is usually done the day before procedure Second step: a 3D TRUS volume is obtained by a real-time TRUS examination in 3 planes (transversal, 60 degree lon- gitudinal turning the probe on the right and on left) by an end fire probe with a rotating 360 degree head. We border the prostate volume in a similar way to MRI process. Third step: automatic elastic fusion of the MRI and ultra- sound volumes is done by the machine’s software pressing a button. We check the correct fusion of the volumes Fourth step: virtual simulation of bioptical tracking with a visual feedback on the fused target volume is done Fifth step: if the virtual simulation of the track is inside the target lesion, we press the button of the needle and a real biopsy is done followed by 3D-TRUS acquisition of the real track with the needle still in the gland. A mean of 2 cores were obtained from each MRI-target area. Then at least a 12-core random biopsy were performed in all patients. In case of stereotactic first round biopsy in biopsy naïve patient (Group B) step 1 and 3 are avoided, we recorded all real track in a 3-D TRUS map. RESULTS Our results are summarized below and displayed in Table 2. Group A (22 patients): 10/22 positive for PCA (overall detection rate of 45.5%). 6 PCA were detected by target biopsy and 4 cancer by random biopsy. Significant prostate cancer (defined as the presence of Gleason pat- tern 4) was detected in 4/10 patients (significant PCA detection rate of 40%), all significant PCA were detected in MRI target biopsy (1/17 PIRADS 3, 2/4 PIRADS 4, 1/1 PIRADS 5). All PCA detected by random biopsy had Gleason score 3 + 3 = 6. Group B (37 biopsy naïve patients): 14/37 positive for PCA (overall detection rate of 37.8%), Significant prostate cancer was detected in 5/14 patients (Significant PCA detection rate of 35,7%). The mean time of the procedure was 42 min (C.I. 22-55) in the initial 10 patients and 27 min in the following 10 patients (C.I. 19-35) in Group A, 27 min (C.I. 19-45) in the initial 10 patients and 17 min in the following 10 patients (C.I. 10-25) in Group B. No significant side effects were recorded in either group (such as fever, urinary retention, urosepsis, and hospital- ization). Table 1. Characteristics of the patients. Group A: patients with a previous negative mapping who underwent to a MRI/US fusion re-biopsy. Group B: biopsy-naïve patients who underwent to a first stereotactic 3-D mapping of the prostate. Group A Group B Number of patients 22 37 Mean age 64 66 Mean PSA 7.7 4.7 DRE positive 2/22 5/37 Mean Prostate Volume 55 46 Total cores 15 14 Mean core from each target 3 PIRADS 3 17/22 PIRADS 4 4/22 PIRADS 5 1/22 Table 2. Results. Group A Group B Overall PCA detection rate 10/22 ( 45.5%) 14/37 (37.8%) Significant PCA detection rate 4/10 (40%) 5/14 (35.7%) PCA in target lesion 6/10 PCA in random biopsy core 4/10 Significant PCA detected in target lesion 4/6 PIRADS 3 1 /6 PIRADS 4 2 /6 PIRADS 5 1/6 Significant PCA in random biopsy core 0/4 Archivio Italiano di Urologia e Andrologia 2016; 88, 4 V. Lacetera, B. Cervelli, A. Cicetti, G. Gabrielloni, M. Montesi, R. Morcellini, G. Parri, E. Recanatini, G. Giglioni, A.B. Galosi, V. Beatrici 298 DISCUSSION We considered many commercial platforms of co-regis- tered MRI/US fusion biopsy devices commercially avail- able. These devices vary by method of co-registration (mechanical, electromagnetic or real-time) and use a differ- ent hardware platform to align the biopsy with the co-reg- istered image. We chose Trinity Koelis because we consid- ered this option to be the best compromise between accu- racy, reproducibility and feasibility in our daily practice. A recent systematic review shows that MRI-TRUS image fusion targeted biopsies detect more clinically significant cancers compared with standard biopsy techniques: the median detection rate of any cancer was 43.4% and 50.5% in the standard biopsy strategy versus MRI-TRUS image fusion biopsy; the median detection of clinically significant disease was 23.6% (range: 4.8-52%) for stan- dard biopsy and 33.3% (range: 13.2-50%) for MRI- TRUS image fusion targeted biopsy However, patient populations differ quite a bit between the different stud- ies regarding the amount of patients with a previous neg- ative biopsy or patients that were biopsy naïve (17). Our overall detection rate was 45.5% and 37.8% in MRI-US fusion biopsy (patients with previous negative biopsy and persistent suspicion of PCA) and in stereotactic biopsy (biopsy naïve patients); clinical significant PCA detection rate was respectively 40% and 35.7%. These results are similar to those reported in the current litera- ture and promising for the future. The main limitations of our study were the small number of patients, differ- ence in expertise of the radiologists, our learning curve of at least the first 10 cases. Until now our main problems using this technique are the following: it is not easy to border the target lesion without radiologist’s help if it is visible only in DWI sequence; because this is a freehand procedure (operator dependent technique) without a probe stepper, even a little movement of the probe in the passage from virtual track simulation to real biopsy could miss the target lesion (especially if the diameter is < 1 cm). CONCLUSIONS MRI/US fusion biopsy in patients with a previous negative mapping but persistent suspicion of PCA represents a use- ful tool to address many of the limitations of contempo- rary systematic re-biopsy (reduce false-negatives, improve risk classification, contribute to the reduction of repeat biopsies and overdetection). Among men with no previ- ous biopsy its role is poorly defined, but we believe that at least a stereotactic first bioptical mapping (recording all bioptical tracks in a 3-D map) can not only increase can- cer detection rate but, if a re-biopsy will be necessary, a MRI-US fusion biopsy can be done using the previous recorded 3-D map, avoiding the same tracks of first map- ping and improving the results of this technique.We believe that among men with suspicion of PCA, stereotac- tic first mapping and MRI/US fusion re- biopsy potential- ly improves risk stratification and reduces understaging, undergrading and the need for repeat biopsies. The opti- mal method for MR targeted biopsy has not yet been established; further comparative studies with standard of practice and evaluation of cost-effectiveness are warranted. Figure 1. First stereotactic 3-D mapping of the prostate in a biopsy- naïve patient. Figure 2. MRI/US fusion re-biopsy in a patients with a previous negative mapping (4 target cores from a MRI lesion with a PIRADS score 3 at right apex plus 9 random cores). Figure 3. Automatic elastic fusion of the MRI and ultrasound volumes is done by the machine’s software. Figure 4. MRI/US fusion target and random re-biopsy: 2 MRI lesions with a PIRADS score of 3 (orange) and 2 MRI lesions with PIRADS 4 (red). 299Archivio Italiano di Urologia e Andrologia 2016; 88, 4 Fusion prostate biopsy REFERENCES 1. Bjurlin MA, Carter HB, Schellhammer P, et al. Optimization of initial prostate biopsy in clinical practice: sampling, labeling and specimen processing. J Urol. 2013; 189:2039. 2. Serefoglu EC, Altinova S, Ugras NS, et al. How reliable is 12-core prostate biopsy procedure in the detection of prostate cancer? Can Urol Assoc J. 2013; 7:E293-E298 3. Mufarrij P, Sankin A, Godoy G, et al. Pathologic outcomes of can- didates for active surveillance undergoing radical prostatectomy. Urology. 2010; 76:689. 4. Walz J, et al. High incidence of prostate cancer detected by satu- ration biopsy after previous negative biopsy series. Eur Urol. 2006; 50:498. 5. Eichler K, et al. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol. 2006; 175:1605. 6. Moran BJ, et al. Re-biopsy of the prostate using a stereotactic transperineal technique. J Urol. 2006; 176:1376. 7. Futterer JJ, et al. Can clinically significant prostate cancer be detected with multiparametric magnetic resonance Imaging? A sys- tematic review of the literature. Eur Urol. 2015; 68:1045. 8. Schoots IG, et al. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound- guided biop- sy: a systematic review and meta-analysis. Eur Urol. 2015; 68:438. 9. Panebianco V, et al. Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a ran- domized study. Urol Oncol. 2015; 33:17 e1. 10. Barentsz JO, Weinreb JC, Verma S, et al. Synopsis of the PI- RADS v2 guidelines for multiparametric prostate magnetic reso- nance imaging and recommendations for use. Eur Urol. 2016; 69:41-49. 11. Vache T, et al. Characterization of prostate lesions as benign or malignant at multiparametric MR imaging: comparison of three scoring systems in patients treated with radical prostatectomy. Radiology. 2014;. 272:446. 12. Barentsz JO, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012; 22:746. 13. Moore CM, Robertson NL, Arsanious N, et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol. 2013; 63:125. 14. Van Hove A, et al. Comparison of image-guided targeted biop- sies versus systematic randomized biopsies in the detection of prostate cancer: a systematic literature review of well-designed stud- ies. World J Urol. 2014; 32:847. 15. Siddiqui MM, et al. Comparison of MR/ultrasound fusion-guid- ed biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA. 2015; 313:390. 16. Epstein JI, Allsbrook WC, Amin MB, Egevad LL, Grading ISUP, ISUP Grading Committee The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grad- ing of prostatic carcinoma. Am J Surg Pathol. 2005; 29:1228-1242. 17. 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; 68:8-19. Correspondence Vito Lacetera, MD, Urologist Vito.Lacetera@gmail.com Bernardo Cervelli, MD, Urologist Bernardo.Cervelli@ospedalimarchenord.it Antonio Cicetti, MD, Urologist Antonio.Cicetti@ospedalimarchenord.it Giuliana Gabrielloni, MD, Urologist Giuliana.Gabrielloni@ospedalimarchenord.it Gianluca Giglioni, MD Gianluca.Giglioni@ospedalimarchenord.it - piallu88@gmail.com Michele Montesi, MD, Urologist Michele.Montesi@ospedalimarchenord.it Roberto Morcellini, MD, Urologist Roberto.Morcellini@ospedalimarchenord.it Gianni Parri, MD, Urologist Gianni.Parri@ospedalimarchenord.it Emilio Recanatini, MD, Urologist Emilio.Recanatini@ospedalimarchenord.it Valerio Beatrici, MD, Urologist Valerio.Beatrici@ospedalimarchenord.it Azienda Ospedaliera Ospedali Riuniti Marche Nord Piazzale Cinelli 4, 61121 Pesaro, Italy Andrea Benedetto Galosi, MD, Associate Professor of Urology galosiab@yahoo.it Clinica Urologica, Università Politecnica delle Marche, Azienda Ospedaliera Ospedali Runiti, Ancona, Italy