Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(4):12992 1 ORIGINAL PAPER tematic prostate biopsy in diagnosing csPCa and reducing unnecessary biopsies; the detection rate for csPCa is cor- related with Prostate Imaging-Reporting and Data System (PI-RADS) score and in selected cases systematic biopsies could be omitted without harbor PCa diagnosis. In this study we have prospectively evaluated the detection rate for PCa performing only mpMRI/fusion targeted biop- sy combined with ipsilateral systematic prostate biopsy. MATERIALS AND METHODS From January 2023 to December 2023, we prospectively evaluated 495 men with clinical suspicion of PCa under- went transperineal systematic (SPBx: 20 cores in both prostatic lobes plus anterior zone) plus mpMRI/transrec- tal ultrasound (TRUS) fusion biopsy in the presence of PIRADS score lesions ≥ 3 (TPBx: 4 cores) (11, 12). Clinical criteria for prostate biopsy were: PSA values > 4 ng/ml and/or suspicion digital rectal examination (DRE) or revaluation (scheduled biopsy) of men enrolled in AS protocol. After institutional review board and ethical committee approval were granted, the informed consent was obtained from all individual participants included in the study. Median PSA was 7.3 ng/ml (range: 3.8-152 ng/ml), digital rectal examination (DRE) was suspicion for PCa in 58/495 (11.7%) cases, 295 vs. 200 underwent ini- tial vs. repeated biopsy, 48 men were enrolled in AS pro- tocol for very low/low risk PCa (13). All the mpMRI index lesions characterized by a PI-RADS (version 2) ≥ 3 under- went targeted cores (TPBx: 4 cores); the procedure was performed transperineally using a tru-cut 18 gauge nee- dle (Bard; Covington, GA, USA) under sedation and antibi- otic prophylaxis. The TPBx was done using an Hitachi 70 Arietta ecograph, Chiba, Japan) supplied by a bi-planar trans-rectal probe (14, 15). The detection rate for PCa of SPBx in the controlateral “negative” mpMRI prostatic lobe of men has been evalu- ated; in detail, the opportunity to omit systematic biop- sy in the hemigland without suspicion mpMRI lesions was evaluated. RESULTS None had significant complications (Clavien-Dindo grade I) from prostate biopsy that needed hospital admission; Introduction: To evaluate the detection rate for prostate cancer (PCa) performing multi- parametric magnetic resonance imaging (mpMRI) fusion target- ed biopsy (TPBx) combined only with ipsilateral systematic prostate biopsy (SPBx). Materials and methods: From January 2023 to December 2023, 495 men with clinical suspicion of PCa underwent transperineal SPBx plus TPBx in the presence of PI-RADS score lesions ≥ 3. Results: In 250/495 men (50.5%) a PCa was found, while 36/250 (14.4%) men had negative mpMRI. In comparison to TPBx, SPBx diagnosed a higher number of indolent PCa, 38.5 vs. 5.8%, respectively; conversely, SPBx demonstrated a higher detection rate for clinically significant PCa (97.3 vs. 85.4%) in the pres- ence of ISUP Grade Group 2 (GG2). In details, rates were high- er in the presence of GG2 (100 vs. 76%), GG3 (85.7 vs. 75.8%) and GG4 (100 vs. 86.4%) tumors. However, in GG5, both SPBx and TPBx diagnosed 100% of csPCa. Furthermore, 89.4% of the cases showed csPCa on the negative mpMRI side. Conclusions: SPBx combined with TPBx maximized csPCa diag- nosis; the use of reduced biopsy scheme limited to ipsilateral side of mpMRI lesion plus TPBx missed 11.6% csPCa. Only in the presence of PI-RADS score 5 SPBx and TPBx diagnosed both 100% of csPCa. Key wORDS: Prostate cancer; mpMRI; Targeted biopsy; Systematic biopsy; Gleason score. Submitted 30 August 2024; Accepted 16 September 2024 INTRODUCTION Prostate cancer (PCa) is the most frequent tumor world- wide in the male population (1), with a high estimated risk of overdiagnosis and overtreatment for men enrolled in PSA screening. In the last years, the use of multipara- metric magnetic resonance imaging (mpMRI) combined with risk calculator including more clinical parameters allowed to improve the diagnosis of clinically significant PCa (csPCa) (2-7). In this respect, the diagnosis and treat- ment of PCa should be tailored for each patient to balance oncological and functional outcomes. Although Active Surveillance (AS) protocols (8) have reduced overtreat- ment of low risk PCa and, in well informed patients, favorable intermediate risk (9, 10) PCa, the necessity of definitive treatment (radical prostatectomy or external radiotherapy) results to worse the quality of life. Multiparametric MRI has improved the accuracy of sys- Multiparametric MRI targeted prostate biopsy: When omit systematic biopsy? Pietro Pepe 1, Ludovica Pepe 2, Vincenzo Fiorentino 2, Mara Curduman 3, Filippo Fraggetta 4 1 Urology Unit, Cannizzaro Hospital, Catania, Italy; 2 Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Messina, Italy; 3 Pathology Unit, Cannizzaro Hospital, Catania, Italy; 4 Pathology Unit, ASP Catania, "Gravina" Hospital, Caltagirone, Italy. DOI: 10.4081/aiua.2024.12992 Summary Archivio Italiano di Urologia e Andrologia 2024; 96(4):12992 P. Pepe, L. Pepe, V. Fiorentino, et al. 2 no patient had bilateral suspicious lesions at mpMRI. In 250/495 (50.5%) men a PCa was diagnosed: 100 (40%) had an International Society of Urological Pathology (16) Grade Group 1 (ISUP GG1)/Gleason score 6, 50 (20%) a GG2/Gleason score 3+4, 28 (21.4%) a GG3/Gleason score 4+3, 26 (15.4%) a GG4/Gleason score 8 and 46 (18.4%) a GG5/Gleason score 9. 36/250 (14.4%) men had nega- tive mpMRI (PI-RADS score < 2): 38.9% (14 cases) were GG1, 33.3% (12 cases) GG2, 16.7% (6 cases) GG3, 11.1% (4 cases) GG4, and 0% GG5. SPBx in comparison with TPBx diagnosed a greater num- ber of indolent PCa equal to 96/250 (38.5%) vs. 14/250 (5.8%) men; on the contrary, SPBx showed an higher detection rate for csPCa (97.3 vs. 85.4%). In details, rates were higher in the presence of GG2 (100 vs. 76%), GG3 (85.7 vs. 78.5%) and GG4 (100 vs. 84.6%), whereas in GG5 SPBx vs. TPBx diagnosed both 100% of csPCa (Table 1). SPBx in comparison with TPBx diagnosed 146/150 (97.3%) vs. 128/150 (85.4%) csPCa, respectively. In total 16/150 (10.6%) men with csPCa had positive sys- tematic cores located only in the ipsilateral side of suspi- cious mpMRI. Out of them, 2/50 (4%) men with GG2 had PI-RADS 3; 10/28 (35.8%) with GG3 had PI-RADS score 3 (2 cases), 4 (6 cases) and 5 (2 cases), respective- ly; 2/26 (7.7%) and 2/46 (4.3%) with GG4 and GG5 had lesions PI-RADS score 4, respectively (Table 1). Performing only TPBx would have spared 14.4% (36/250) biopsies and adding systematic cores in the ipsi- lateral side of TPBx 11.6% csPCa located in the contro- lateral prostatic lobe with negative mpMRI would have missed. DISCUSSION The use of mpMRI has increased the diagnosis of csPCa with a false negative rate equal to 15-20% of the cases; therefore, systematic biopsies, still today, should be com- bined with targeted cores to improve PCa diagnosis (17). It remains unknown whether csPCa is missed due to the limited sensitivity of MRI, the suboptimal image fusion, the biopsy technique and strategy, expertise of the sur- geon or a combination of these. If the diagnosis of PCa is based on “MRI pathway” (18) the patients should be advised of false negative rate for csPCa but, at the same time, the mor- bidity of the procedure could result less invasive because the lower num- ber of needle cores. Recently, a reduced-core prostate biopsy strategy confined to the ipsi- lateral emigland of suspicious mpMRI including “perilesional cores” has been proposed to decrease the number of systematic cores, but, still today, the literature data are not in agreement and the detection rate for csPCa is correlated to different PI-RADS scores (19). Bourgeno et al. (20) in 2.387 men submitted to different prostate biopsy schemes reported that the added value of contralateral systemat- ic biopsy was negligible in terms of cancer detection (6.1% of the cases) and upgrading rates. Hegens et al. (21) reported in 235 patients that TPBx plus- perilesional biopsy approach detected 96.8% csPCa reducing the diagnosis of indolent PCa in 12.8% of the cases. Deniffel et al. (22) in 745 men submitted to mpMRI TPBx plus systematic biopsy reported that standard cores could be avoided only in men with PI-RADS score 5 and/or previous negative biopsy, missing 1 vs. 2% of csPCa and avoiding 27 vs. 58% of systematic procedures. On the other hand, Sawhney et al. (23) reported in 490 men that about 20% of men with unilateral MRI lesions and csPCa on targeted biopsy were found to have contro- lateral csPCa on systematic biopsies. Phelps et al. (24) in 212 men with mpMRI-visible intraprostatic lesions demonstrated that TPBx alone diagnosed 81.5% PCa, on the contrary 7.6% had controlateral involvement and 10.9% had bilateral PCa and concluded that TPBx com- bined with systematic biopsies maximizes csPCa diagno- sis. Hou et al. (25) in 229 patients showed that the bene- fit of systematic biopsy added to TPBx was restricted to smaller PI-RADS score 3-4 resulting not useful for the diagnosis of csPCa in the presence of PI-RADS score lesions 5 and larger (> 1 cm) PI-RADS score 3-4 allowing to reduce systematic biopsies in 44.5% of the cases with- out compromising csPCa diagnosis. The discordant data reported in literature are, probably, correlated with the clinical parameters (DRE, clinical stage, PSA values), PI- RADS score values and number of needle cores per- formed by systematic prostate biopsy; in general, only in the presence of PI-RADS score 5 controlateral SPBx could be omitted. Anyway, omitting controlateral SPBx a rele- vant number of csPCa could be definitively missed espe- cially in men candidate to radiotherapy. Recently, new prostate targeted strategies have been proposed; the use of transrectal microultrasound (26) and PSMA PET/CT (27- 30) demostrated good accuracy in diagnosing csPCa per- forming targeted biopsy when compared with mpMRI accuracy, but the results were obtained in men enrolled in clinical trials and/or in limited number of cases. In our series, among 250/495 (50.5%) PCa 150 (60%) where csPCa and 36 (14.4%) had negative mpMRI (PI- RADS score ≤ 2). SPBx in comparison with TPBx diag- nosed a greater number of indolent PCa (38.5 vs. 5.8%); Table 1. Biopsy findings in the 250 men with prostate cancer (PCa) submitted to systematic (SPBx) and targeted biopsy (TPBx). Overall PCa PI-RADS ≤ 2 Positive Positive PCa only Number of Median GPC 250 36 (14.4%) TPBx SPBx in ipsilateral side positive cores PSA median GG1/GS 6 14 (39%) 54 (54%) 96 (96%) 0 2 4.2 25% 100 cases GG2/GS 3+4 12 (33.3%) 38 (76%) 50 (100%) 2/50 (4%) 8 5.9 40% 50 cases GG3/GS 4+3 6 (16.6%) 22 (78.5%) 24 (85.7%) 10/28 (35.7%) 10 8.6 55% 28 cases GG4/GS 8 4 (11.1%) 22 (84.6%) 26 (100%) 2/26 (7.7%) 15 12.5 60% 26 cases GG5/GS 4+5 0 100% 100% 2/46 (4.3%) 18 19.2 85% 46 cases GS: Gleason score; PSA: Prostate specific antigen; GPC: greatest percentage of cancer; PI-RADS: Prostate Imaging-Reporting and Data System; GG: ISUP Grade Group; mpMRI: multiparametric magnetic resonance image Archivio Italiano di Urologia e Andrologia 2024; 96(4):12992 3 Targeted vs. systematic prostate biopsy on the ther hand, SPBx showed an higher detection rate for csPCa (97.3 vs. 85.4%). In detail, only 16/150 (10.6%) men with csPCa had posi- tive cores located only in the ipsilateral side of suspicious mpMRI: 2/50 (4%) men with GG2; 10/28 (35.8%) with GG3; 2/26 (7.7%) and 2/46 (4.3%) with GG4 and GG5, respectively. Only men with PI-RADS score 5 had a detec- tion rate for csPCa equal to 100% performing TPBx vs. SPBx (Table 1). TPBx combined with ipsilateral SPBx alone would have missed 27.2% of PCa irrispective of PI- RADS score and 11.6% were csPCa; in addition, quantita- tive histological findings useful for local staging of PCa and planification of definitive treatment (i.e. nerve sparing prostatectomy; intensity modulated radiotherapy) would have missed. Finally, performing only TPBx would have spared 14.4% biopsies missing the presence of csPCa also in the negative mpMRI side in 89.4% of the cases. Regarding our results, some consideration should be done. 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Correspondence Pepe Pietro, MD (Corresponding Author) piepepe@hotmail.com Urology Unit, Cannizzaro Hospital, 95126 Catania, Italy Ludovica Pepe, MD ludopepe97@gmail.com Vincenzo Fiorentino, MD vincenzo.fiorentino@unime.it Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98125 Messina, Italy Mara Curduman, MD mara.curduman@aoec.it Pathology Unit, Cannizzaro Hospital, 95126 Catania, Italy Filippo Fraggetta, MD filippofra@hotmail.com Pathology Unit, ASP Catania, "Gravina" Hospital, 95041 Caltagirone, Italy Conflict of interest: The authors declare no potential conflict of interest.