Is MRI/US-guided fusion biopsy ready to replace systematic biopsy in detecting clinically significant prostate carcinoma? – A retrospective study

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Methods: A retrospective, single-center analysis was performed on 851 (Median age 70) patients who underwent combined FB and SB when PIRADS 3 or higher was indicated on mpMRI between June 2019 and November 2024. The highest ISUP-GG was compared between the two biopsy methods with analysis of discordant findings between the methods. Furthermore, the detection rates of csPCa were compared between the TP and TR access routes. Results: FB identified higher ISUP GG in 70.97% of discordant cases, with FB detecting csPCa in 42.2%of patients compared to 28.5% by SB ( p < 0.001). Insignificant PCa was detected with similar frequency by both methods, with a close majority for the SB (30.3%) vs. FB (28.2%). Statistically significant association in csPCa detection rates was found between TP (50.1%) and TR (43.0%) approaches ( p = 0.038). Conclusion: FB significantly improves the detection of higher ISUP GG and csPCa compared to SB. However, the use of both methods together provides the most reliable diagnosis. Cancer of prostate Image-Guided biopsy Transrectal approach Transperineal approach Clinical significance Figures Figure 1 Figure 2 Figure 3 Introduction Prostate cancer (PCa) still has a high prevalence and mortality globally, leading to a high economic as well as psychological burden [ 1 ]. PCa is graded using the ISUP (International Society of Urological Pathology) classification (Grades 1–5), based on the Gleason score, to determine aggressiveness [ 2 ]. Within the ISUP-GG classification, Group 1 is categorized as clinically insignificant as they remain asymptomatic in almost all cases [ 3 ], though they may progress leading to active surveillance (AS) following the diagnosis. Autopsy studies reveal many latent prostate cancers, therefore PSA testing with subsequent biopsy of asymptomatic men lead to an increased detection of these clinically insignificant cancers with the risk of overdiagnosis and overtreatment [ 4 , 5 ]. Accurate grading of PCa is crucial for prognosis and treatment decisions. In the past years there has been significant changes in the diagnostic approach for detecting PCa with assistance of multiparametric magnetic resonance imaging (mpMRI), combining high resolution T2-weighted (T2w) sequences, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences [ 6 ]. MpMRI findings, combined with biopsy results are used to guide therapy decisions, particularly for patients under active surveillance (AS). Standardized reporting using the modified PI-RADS v2.1 (Prostate Imaging Reporting and Data System Version 2.1: 2019), ensures consistency in interpretation [ 7 ]. Advances in biopsy techniques, including fusion biopsy (FB), which integrates mpMRI with real-time ultrasound (US), have improved accuracy compared to traditional systematic biopsy (SB) [ 8 ]. Cognitive FB relies on the physician's mapping skills, while software-assisted FB uses real-time fusion for precise targeting [ 9 ]. Existing literature states that FB detects more clinically significant PCa and fewer insignificant tumors compared to SB, although neither method alone captures all cases [ 10 – 12 ]. Combining both methods yields the most reliable detection, with a reduced risk of missing clinically significant cancers [ 13 ]. Additionally, transperineal (TP) access has been shown to improve biopsy accuracy, particularly for harder-to-reach prostate zones, compared to transrectal (TR) access [ 14 ]. With rising concern regarding the economic burden, the question remains if with advancing medical precision, we can forego systematic biopsy to minimize the cost factor. Adding to that, the gaining access to mpMRI with higher detection rates of suspicious cancers, there is also a raise in biopsy requests with additional time burden in clinical practice. This study aims to evaluate, whether results from FB alone allows replacement of SB in detecting clinically significant PCa and validates the impact of biopsy access (TP vs. TR) on outcomes. Materials and methods This study is an Institutional Review Board (IRB) approved, monocentric, retrospective analysis of male patients, who underwent systematic biopsy followed by fusion biopsy in the same session between June 7, 2019, and November 30, 2024. From 2019 to 2022, the biopsy access route was predominantly transrectal, while from 2023 onwards, the surgical approach was primarily transperineal. All patients who had received a combined biopsy (SB and FB) since the implementation of MRI/US-targeted FB were identified. Patient data were obtained from the database, including radiology, pathology, and laboratory findings. Patients who had undergone only SB or only FB, gold marker implantation, or lacked MRI, pathology results, PSA density, or PI-RADS scores were excluded (Fig. 1 ). Collected data included patient demographics, biopsy details (access route, ISUP grade per core), MRI-marked lesion locations, and histopathological findings. Pre-biopsy planning of MRI-marked lesions within the prostate and software assisted fusion biopsy was performed using Biojet software (MTT GmbH, Lüneburg, Germany) (Fig. 2 ). Since this is a retrospective study, the sample size is determined by the availability of existing data. Therefore, no formal sample size calculation was made. MRI/US-guided FB has been standard since 2019 for PIRADS ≥ 3 lesions, with TP access preferred since 2023. A total of 851 patients were included (mean age 70 ± 33.93 years). For comparing biopsy methods (SB vs. FB) and access routes (TR vs. TP), the highest ISUP Grade Group (ISUP-GG) obtained from each biopsy method was used. For the purposes of this study, only the histopathological results were used for risk group classification (Fig. 3 ). Statistical analysis Analyses were performed using IBM® SPSS® Statistics 30. First, absolute frequencies and percentages of ISUP-GG per method (SB vs. FB) were calculated. Second, the results of both methods were presented together in a contingency table (6 x 6 ISUP-GG), allowing the determination of concordant and discordant findings between the methods, which were further quantified by absolute frequencies and percentages (by row and column). Concordance was calculated using Goodman and Kruskal's statistics. To compare ISUP-GG detection between SB and FB, the Wilcoxon signed-rank test was used due to the ordinal nature of ISUP-GG, and the measurements are dependent (two measurements per patient). Therefore, the non-parametric Wilcoxon signed-rank test was selected. Given the directional hypothesis, a one-sided p-value was reported. For assessing whether TP detects more clinically significant PCa (ISUP GG > 1) than TR, a chi-square independence test was performed. A contingency table categorized biopsy route (TP vs. TR) and highest ISUP-GG, dichomotized as insignificant (0/1) or significant PCa (2–5). Each patient was either biopsied transperineally or transrectally. All patients underwent both FB and SB via the same route in the same session. Initially, the analysis compared all patients who were biopsied via TP with those biopsied via TR route, followed by a matched cohort (age and PSA density) to increase statistical power. The significance level was set at 5%. Since two hypotheses were tested in this study, the significance level for each hypothesis was adjusted to 2.5% using Bonferroni's method. Finally, an exploratory Spearman correlation was calculated between GG and PSA density. Results A total of 851 patients underwent fusion biopsy (FB) followed by systematic biopsy (SB) in the same session. From those, 416 biopsies (48.9%) were performed using the transrectal (TR) approach, while 435 biopsies (51.1%) were performed via transperineal access (TP). Among the 851 included patients, both biopsy methods detected the same ISUP-GG in 479 patients (56.3%) while the remaining 372 patients (43.7%) showed discordant results ( see Table 1, 2 ). In 70.9% of discordant cases, FB detected a higher ISUP-GG compared to SB ( p < 0.001) with a strong overall correlation (Goodman and Kruskal’s γ = 0.658, p < 0.001, see Table S1 ). Clinically insignificant PCa (ISUP-GG 1) was detected with similar frequency by both methods (30.3% for SB vs. 28.2% for FB). However, FB was superior to SB in detecting clinically significant PCa (csPCa, ISUP-GG 2–5). SB missed PCa in 43% (153 patients), of which 51.6% (79 patients) were classified as insignificant (GG 1) and 48.3% (74 patients) as csPCa (GG 2–5) according to FB results. Similarly, SB missed csPCa in 31.0% (80 patients). FB missed PCa in 21.8% (55 patients), of which 65.4% (36 patients) were classified as insignificant PCa and 34.5% (19 patients) as csPCa. In 240 cases FB misclassified csPCA as insignificant in 7.9% (19 patients). Considering the discordances in ISUP-GG detection by both biopsy methods, the impact of these discordant findings on the classification of PCa into clinically relevant risk groups ( see Fig. 2 ) is illustrated in the subsequent cross-tabulations ( see Table 3, 4 ). Risk classification based on SB alone underestimated PCa in a significant number of patients, with 43.8% requiring upgrading when FB was considered (22.6% to low-risk, 14.3% to intermediate risk, 6.9% to high-risk). Similarly, FB results also underestimated risk in some cases compared to SB. The data further demonstrated a significant correlation between PSA density and the detected grade for FB (Spearman r = 0.303, p < 0.001) and SB (Spearman r = 0.293, p < 0.001): the higher the PSA-D, the higher the ISUP-GG assigned based on biopsy ( see Table S2 ). Of the 851 patients, 416 underwent TR biopsy and 435 underwent TP biopsy. We compared the detection rates of csPCa (GG2-5) for each access route. Access route analysis showed higher csPCa detection rates in TP (50.1%) than TR (43.0%) approach ( see Table 5 ). The chi-square independence test found a statistically significant association between csPCa detection rates and the access routes (p = 0.038) ( see Table S3 ). When comparing the PSA density, the arithmetic mean value of patients with transrectal approach was 0.204 ng/mL/ccm (SD = 0.182) and for patients with transperineal approach 0.232 ng/mL/ccm (SD = 0.221) ( see Table S4 ) with statistically significant deviation (Independent Samples t-test = 0.048). The age of both groups was comparable between TP with a mean age of 70 years and TR with 71 years (Independent Samples t-test, p = 0.690). Discussion This study including 851 patients undergoing combined SB and FB in the same session demonstrated a significantly better detection rate of csPCa with FB compared to SB ( p < 0.001). However, the combination of both methods improved overall detection. Further analysis showed that the TP route was significantly superior to the TR approach for csPCa detection. Since both biopsy methods were performed on all patients, this study allows a robust comparison of their diagnostic performance (Goodman and Kruskal’s γ = 0.658, p < 0.001). Cross-table results ( see Tables 1 and 3 ) indicate FB detected ISUP-GGs 2–5 more frequently, while SB identified slightly more cases of no PCa or ISUP-GG 1 categorized as ncsPCa (see Fig. 2 ). Nonetheless, these results also indicate that SB detected a higher ISUP-GG in a notable proportion of patients, which could impact prognostic accuracy and treatment recommandations if only FB had been used. Such misclassification would be particularly problematic if a csPCa was completely overlooked, and the patient was incorrectly assigned an ISUP-GG 0. This could lead to false reassurance and delayed follow-up. Similarly, underestimating a higher ISUP-GG might result in missing the need for a more aggressive treatment, particularly in rapidly progressing, aggressive PCa cases where an active surveillance (AS) approach might otherwise be recommended. A limitation of this study is the inclusion of biopsy naïve patients and active surveillance patients, where prior biopsy may alter prostate anatomy, potentially affecting fusion biopsy accuracy. Furthermore, the biopsies were performed by fourteen different urology specialists, ranging from residents to specialists with over 10 years’ experience in the field. Our results align with previous studies. Ahdoot et al. (n = 2103;2020) found a significantly higher detection rate for ISUP-GG 3–5 with FB, while SB still identified a considerable number of PCa cases across all ISUP-GGs [ 10 ]. Studies by Plousard et al. (2019), Dorfinger et al. (2022), and Kasivisvanathan et al. (2018) support the combination of both methods to improve csPCa detection [ 11 , 13 , 15 ]. However, Kasivisvanathan et al. showed that ISUP-GG 1 PCa was detected more than twice as often with SB, these results also correspond with the study carried out by Kaufmann et al. (2022) [ 16 ]. Similarly, Siddiqui et al. (2015) reported increased csPCa detection with FB and fewer ncsPCa cases, while in the study conducted by Mortezavi et al. (2018) SB outperformed FB due to a high number of false negative cases [ 12 , 17 ]. In a recent study by Dagnino et al. (2024) the authors show promising results with the use of combining microultrasound (micro-US) and mpMRI with the potential of avoiding unnecessary SB [ 18 ]. Economic analysis of biopsy methods is an important factor in clinical practice, considering the cost-effectiveness. A recent systematic review conducted by Llewellyn et al. in 2024 evaluated the cost-effectiveness of software fusion biopsy technologies compared to cognitive fusion biopsies and further assessment whether concomitant systematic biopsy influences cost-effectiveness [ 19 ]. The study suggests that software fusion might be worth the additional cost, but since its diagnostic superiority over cognitive fusion is uncertain, the economic conclusions are weaker. Noujeim et al. (2023) proposed perilesional biopsy as a possible alternative to the combined FB/SB with comparable detection rates [ 20 ]. In clinical practice, SB remains crucial as it identifies csPCa cases missed by FB, aiding treatment decisions such as nerve-sparing surgery or radical prostatectomy. A significant factor influencing diagnostic accuracy of mpMRI is the variability in the positive predictive value (PPV), particularly for PI-RADS 3 lesions as stated by Mazzone et al. (2021), reinforcing SB´s role in detection [ 21 ]. Considering this, this could be a potential influencing factor for our study as we included patients with PIRADS 3, thus adding more value to the systematic approach for detection of PCa. All mpMRI images in this study were double read by two radiologists prior to fusion biopsy. Meaning, the prior given PIRADS score was upgraded or downgraded according to the expertise of the second radiologist with over 10 years of experience with prostate MRI. The prior given results may be a potential factor for inter-reader variability. Regarding access routes, our study demonstrated a significantly higher csPCa detection rates with TP approach. This is consistent with Ber et al. (n = 77; 2020) and Zattoni et al. (n = 5241; 2022), who found a higher csPCa detection using TP approach [ 22 , 23 ]. In a more recent study conducted by Liu et. al (2024), the results of the study reported superior overall detection rate with TP biopsy but significant difference in detecting csPCa, further no benefit was noted with additional target biopsy after systematic biopsy [ 24 ]. El-Achar et. al (2022) and Kaneko et. al (2023) found that TP biopsies resulted in larger core samples and fewer complications [ 25 , 26 ]. Systematic reviews by Rai et al. (2021) and Paesano et al. (2023) further support TP´s superiority, particularly for anterior tumors and lower infection risks [ 27 , 28 ]. While prior reviews did not establish TP as superior, recently conducted studies with larger cohorts have confirmed its advantages, leading the EAU to recommend TP since 2022 [ 29 – 31 ]. A limiting factor in our study was the differences in PSA-density between TP and TR groups, which may influence predictive power. However, the observed difference (0.028 ng/mL/ccm) is clinically negligible, as patients with PSA-density > 0.20 ng/mL/ccm are categorized as high risk for the risk-adapted biopsy decision [ 32 , 33 ]. Conclusion In conclusion, we have demonstrated with this study that FB detected higher ISUP-GG values than SB when both methods were performed in the same session. FB was also superior in detecting csPCa. SB slightly outperformed FB in regard to detection of non-significant PCa. However, FB should not be used as a standalone method, as it could miss or downgrade some csPCa cases compared to additional SB in a non-negligible proportion of patients. Additionally, the study showed statistically significant difference in detecting csPCa when comparing the access routes and therefore TP should be preferred, further adding to a lower risk of possibly associated complications. Further research is needed to explore the causes of missed detections or misclassifications with FB, especially regarding discordances between methods. Future studies incorporating AI in the evaluation of MRI images may help improve FB accuracy and potentially allow FB to be used as a standalone method. Abbreviations MRI-US: Magnetic Resonance Imaging-Ultrasound FB: Fusion Biopsy SB: Systematic Biopsy csPCa: Clinically Significant Prostate Cancer TP: Transperineal TR: Transrectal mpMRI: multiparametric Magnetic Resonance Imaging ISUP-GG: International Society of Urological Pathology Grade Group PSA: Prostate-Specific Antigen ncsPCa: Clinically Insignificant Prostate Cancer AS: Active Surveillance RCT: Randomized Controlled Trial EAU: European Association of Urology Declarations Funding No funding was received for conducting this study Competing interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of University Karl Landsteiner approved this study. Authors´ Contribution A Ökrösi: Protocol/Project development, Data collection and management, Data analysis, Manuscript writing A Peltzer Svarer: Data collection and management, Data analysis G Rosta: Protocol/project development, Manuscript editing B Wambacher: Manuscript editing G Heinz: Protocol/project development, Manduscript editing References Ferlay J, Ervik M, Lam F, et al (2024) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Egevad L, Delahunt B, Srigley JR, Samaratunga H (2016) International Society of Urological Pathology (ISUP) grading of prostate cancer - An ISUP consensus on contemporary grading. 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World J Surg Oncol 17:31. https://doi.org/10.1186/s12957-019-1573-0 Loy LM, Lim GH, Leow JJ, et al (2020) A systematic review and meta-analysis of magnetic resonance imaging and ultrasound guided fusion biopsy of prostate for cancer detection-Comparing transrectal with transperineal approaches. Urol Oncol 38:650–660. https://doi.org/10.1016/j.urolonc.2020.04.005 EAU Guidelines Edn. presented at the EAU Annual Congress Paris 2024. ISBN 978-94-92671-23-3 Schoots IG, Padhani AR (2021) Risk-adapted biopsy decision based on prostate magnetic resonance imaging and prostate-specific antigen density for enhanced biopsy avoidance in first prostate cancer diagnostic evaluation. BJU Int 127:175–178. https://doi.org/10.1111/bju.15277 Stevens E, Truong M, Bullen JA, et al (2020) Clinical utility of PSAD combined with PI-RADS category for the detection of clinically significant prostate cancer. Urologic Oncology: Seminars and Original Investigations 38:846.e9-846.e16. https://doi.org/10.1016/j.urolonc.2020.05.024 Tables Tables 1-5 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files MRIUSFusionBiopsySupplementaryMaterialWJU.docx Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6466948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449131873,"identity":"b96929ae-bdd6-40b3-8335-0aa8a1741fcf","order_by":0,"name":"Alexandra Ökrösi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Ökrösi","suffix":""},{"id":449131874,"identity":"a9e2cb1b-f00e-4acb-a3c1-950415e247a6","order_by":1,"name":"Alexander Peltzer-Svarer","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Peltzer-Svarer","suffix":""},{"id":449131875,"identity":"f1c6ee19-4d24-45c8-abbd-cf83dd6dcb16","order_by":2,"name":"Gabor Rosta","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gabor","middleName":"","lastName":"Rosta","suffix":""},{"id":449131876,"identity":"a89d44d1-3ad5-4880-8762-798e802478f1","order_by":3,"name":"Bernhard Wambacher","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Bernhard","middleName":"","lastName":"Wambacher","suffix":""},{"id":449131877,"identity":"2f6b6598-0945-4155-bdbc-fc66b2e36df2","order_by":4,"name":"Gertraud Heinz","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Gertraud","middleName":"","lastName":"Heinz","suffix":""}],"badges":[],"createdAt":"2025-04-17 01:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6466948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6466948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82161959,"identity":"9c1f6fea-6e1f-4120-8aa3-94de56d69238","added_by":"auto","created_at":"2025-05-07 08:40:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":30504,"visible":true,"origin":"","legend":"\u003cp\u003eStudy design; ISUP GG International Society of Urological Pathology Grade Group, SB Systemic biopsy, FB Fusion biopsy, TP Transperineal biopsy, TR Transrectal biopsy.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/a836d1e3d8f1914a1d7fba9a.jpg"},{"id":82161962,"identity":"0cfd075e-0aa7-4427-8413-554576fe43d3","added_by":"auto","created_at":"2025-05-07 08:40:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":107328,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative images of transperineal MRI/US prostate fusion biopsy planning; (\u003cstrong\u003eA\u003c/strong\u003e) Pre biopsy mpMRI showing a PIRADS score 4 lesion (blue arrow) in the peripheral zone; (\u003cstrong\u003eB\u003c/strong\u003e) representative axial view of transperineal MRI/US fusion prostate biopsy planning. T2WI T2 weighted image, DCE dynamic contrast-enhanced, DWI diffusion weighted imaging, ADC apparent diffusion coefficient.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/cf2713b933e442db8824213a.jpg"},{"id":82161961,"identity":"60bef464-dd90-4642-868d-a62fbd5e89e5","added_by":"auto","created_at":"2025-05-07 08:40:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47151,"visible":true,"origin":"","legend":"\u003cp\u003eBased on the EAU (European Association of Urology) risk groups for biochemical recurrence of prostate cancer. ISUP International Society for Urological Pathology; GG Grade group.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/90a075e685a1db3cc0288267.jpg"},{"id":83293647,"identity":"d8cb74e8-25ee-4573-8c24-15996366a27f","added_by":"auto","created_at":"2025-05-22 13:23:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":618180,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/89a9cd04-f83c-4acc-a64b-0d0a11db9a98.pdf"},{"id":82162741,"identity":"a1e54caf-1145-49cb-9c7f-c68e926447f9","added_by":"auto","created_at":"2025-05-07 08:48:51","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":331618,"visible":true,"origin":"","legend":"","description":"","filename":"MRIUSFusionBiopsySupplementaryMaterialWJU.docx","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/7b5bcfc17c01ba9f5e039f88.docx"},{"id":82163860,"identity":"5300d351-90c7-4605-8d44-f75f0a18c0cb","added_by":"auto","created_at":"2025-05-07 08:56:51","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":712773,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6466948/v1/e7f61826e165f3486573b235.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is MRI/US-guided fusion biopsy ready to replace systematic biopsy in detecting clinically significant prostate carcinoma? – A retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstate cancer (PCa) still has a high prevalence and mortality globally, leading to a high economic as well as psychological burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. PCa is graded using the ISUP (International Society of Urological Pathology) classification (Grades 1\u0026ndash;5), based on the Gleason score, to determine aggressiveness [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Within the ISUP-GG classification, Group 1 is categorized as clinically insignificant as they remain asymptomatic in almost all cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], though they may progress leading to active surveillance (AS) following the diagnosis. Autopsy studies reveal many latent prostate cancers, therefore PSA testing with subsequent biopsy of asymptomatic men lead to an increased detection of these clinically insignificant cancers with the risk of overdiagnosis and overtreatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Accurate grading of PCa is crucial for prognosis and treatment decisions. In the past years there has been significant changes in the diagnostic approach for detecting PCa with assistance of multiparametric magnetic resonance imaging (mpMRI), combining high resolution T2-weighted (T2w) sequences, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. MpMRI findings, combined with biopsy results are used to guide therapy decisions, particularly for patients under active surveillance (AS). Standardized reporting using the modified PI-RADS v2.1 (Prostate Imaging Reporting and Data System Version 2.1: 2019), ensures consistency in interpretation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Advances in biopsy techniques, including fusion biopsy (FB), which integrates mpMRI with real-time ultrasound (US), have improved accuracy compared to traditional systematic biopsy (SB) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Cognitive FB relies on the physician's mapping skills, while software-assisted FB uses real-time fusion for precise targeting [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Existing literature states that FB detects more clinically significant PCa and fewer insignificant tumors compared to SB, although neither method alone captures all cases [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Combining both methods yields the most reliable detection, with a reduced risk of missing clinically significant cancers [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, transperineal (TP) access has been shown to improve biopsy accuracy, particularly for harder-to-reach prostate zones, compared to transrectal (TR) access [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. With rising concern regarding the economic burden, the question remains if with advancing medical precision, we can forego systematic biopsy to minimize the cost factor. Adding to that, the gaining access to mpMRI with higher detection rates of suspicious cancers, there is also a raise in biopsy requests with additional time burden in clinical practice.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate, whether results from FB alone allows replacement of SB in detecting clinically significant PCa and validates the impact of biopsy access (TP vs. TR) on outcomes.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThis study is an Institutional Review Board (IRB) approved, monocentric, retrospective analysis of male patients, who underwent systematic biopsy followed by fusion biopsy in the same session between June 7, 2019, and November 30, 2024. From 2019 to 2022, the biopsy access route was predominantly transrectal, while from 2023 onwards, the surgical approach was primarily transperineal. All patients who had received a combined biopsy (SB and FB) since the implementation of MRI/US-targeted FB were identified. Patient data were obtained from the database, including radiology, pathology, and laboratory findings. Patients who had undergone only SB or only FB, gold marker implantation, or lacked MRI, pathology results, PSA density, or PI-RADS scores were excluded (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Collected data included patient demographics, biopsy details (access route, ISUP grade per core), MRI-marked lesion locations, and histopathological findings. Pre-biopsy planning of MRI-marked lesions within the prostate and software assisted fusion biopsy was performed using Biojet software (MTT GmbH, L\u0026uuml;neburg, Germany) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Since this is a retrospective study, the sample size is determined by the availability of existing data. Therefore, no formal sample size calculation was made. MRI/US-guided FB has been standard since 2019 for PIRADS \u0026ge; 3 lesions, with TP access preferred since 2023. A total of 851 patients were included (mean age 70 \u0026plusmn; 33.93 years). For comparing biopsy methods (SB vs. FB) and access routes (TR vs. TP), the highest ISUP Grade Group (ISUP-GG) obtained from each biopsy method was used. For the purposes of this study, only the histopathological results were used for risk group classification (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAnalyses were performed using IBM\u0026reg; SPSS\u0026reg; Statistics 30. First, absolute frequencies and percentages of ISUP-GG per method (SB vs. FB) were calculated. Second, the results of both methods were presented together in a contingency table (6 x 6 ISUP-GG), allowing the determination of concordant and discordant findings between the methods, which were further quantified by absolute frequencies and percentages (by row and column). Concordance was calculated using Goodman and Kruskal's statistics. To compare ISUP-GG detection between SB and FB, the Wilcoxon signed-rank test was used due to the ordinal nature of ISUP-GG, and the measurements are dependent (two measurements per patient). Therefore, the non-parametric Wilcoxon signed-rank test was selected. Given the directional hypothesis, a one-sided p-value was reported. For assessing whether TP detects more clinically significant PCa (ISUP GG\u0026thinsp;\u0026gt;\u0026thinsp;1) than TR, a chi-square independence test was performed. A contingency table categorized biopsy route (TP vs. TR) and highest ISUP-GG, dichomotized as insignificant (0/1) or significant PCa (2\u0026ndash;5). Each patient was either biopsied transperineally or transrectally. All patients underwent both FB and SB via the same route in the same session. Initially, the analysis compared all patients who were biopsied via TP with those biopsied via TR route, followed by a matched cohort (age and PSA density) to increase statistical power. The significance level was set at 5%. Since two hypotheses were tested in this study, the significance level for each hypothesis was adjusted to 2.5% using Bonferroni's method. Finally, an exploratory Spearman correlation was calculated between GG and PSA density.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 851 patients underwent fusion biopsy (FB) followed by systematic biopsy (SB) in the same session. From those, 416 biopsies (48.9%) were performed using the transrectal (TR) approach, while 435 biopsies (51.1%) were performed via transperineal access (TP).\u003c/p\u003e \u003cp\u003eAmong the 851 included patients, both biopsy methods detected the same ISUP-GG in 479 patients (56.3%) while the remaining 372 patients (43.7%) showed discordant results (\u003cem\u003esee Table\u0026nbsp;1, 2\u003c/em\u003e). In 70.9% of discordant cases, FB detected a higher ISUP-GG compared to SB (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with a strong overall correlation (Goodman and Kruskal\u0026rsquo;s γ\u0026thinsp;=\u0026thinsp;0.658, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cem\u003esee Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/em\u003e). Clinically insignificant PCa (ISUP-GG 1) was detected with similar frequency by both methods (30.3% for SB vs. 28.2% for FB). However, FB was superior to SB in detecting clinically significant PCa (csPCa, ISUP-GG 2\u0026ndash;5). SB missed PCa in 43% (153 patients), of which 51.6% (79 patients) were classified as insignificant (GG 1) and 48.3% (74 patients) as csPCa (GG 2\u0026ndash;5) according to FB results. Similarly, SB missed csPCa in 31.0% (80 patients). FB missed PCa in 21.8% (55 patients), of which 65.4% (36 patients) were classified as insignificant PCa and 34.5% (19 patients) as csPCa. In 240 cases FB misclassified csPCA as insignificant in 7.9% (19 patients). Considering the discordances in ISUP-GG detection by both biopsy methods, the impact of these discordant findings on the classification of PCa into clinically relevant risk groups (\u003cem\u003esee\u003c/em\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e) is illustrated in the subsequent cross-tabulations (\u003cem\u003esee Table\u0026nbsp;3, 4\u003c/em\u003e). Risk classification based on SB alone underestimated PCa in a significant number of patients, with 43.8% requiring upgrading when FB was considered (22.6% to low-risk, 14.3% to intermediate risk, 6.9% to high-risk). Similarly, FB results also underestimated risk in some cases compared to SB. The data further demonstrated a significant correlation between PSA density and the detected grade for FB (Spearman r\u0026thinsp;=\u0026thinsp;0.303, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and SB (Spearman r\u0026thinsp;=\u0026thinsp;0.293, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001): the higher the PSA-D, the higher the ISUP-GG assigned based on biopsy (\u003cem\u003esee Table S2\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eOf the 851 patients, 416 underwent TR biopsy and 435 underwent TP biopsy. We compared the detection rates of csPCa (GG2-5) for each access route. Access route analysis showed higher csPCa detection rates in TP (50.1%) than TR (43.0%) approach (\u003cem\u003esee Table\u0026nbsp;5\u003c/em\u003e). The chi-square independence test found a statistically significant association between csPCa detection rates and the access routes (p\u0026thinsp;=\u0026thinsp;0.038) (\u003cem\u003esee Table S3\u003c/em\u003e). When comparing the PSA density, the arithmetic mean value of patients with transrectal approach was 0.204 ng/mL/ccm (SD\u0026thinsp;=\u0026thinsp;0.182) and for patients with transperineal approach 0.232 ng/mL/ccm (SD\u0026thinsp;=\u0026thinsp;0.221) (\u003cem\u003esee Table S4\u003c/em\u003e) with statistically significant deviation (Independent Samples t-test\u0026thinsp;=\u0026thinsp;0.048). The age of both groups was comparable between TP with a mean age of 70 years and TR with 71 years (Independent Samples t-test, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.690).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study including 851 patients undergoing combined SB and FB in the same session demonstrated a significantly better detection rate of csPCa with FB compared to SB (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, the combination of both methods improved overall detection. Further analysis showed that the TP route was significantly superior to the TR approach for csPCa detection. Since both biopsy methods were performed on all patients, this study allows a robust comparison of their diagnostic performance (Goodman and Kruskal\u0026rsquo;s γ\u0026thinsp;=\u0026thinsp;0.658, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cross-table results (\u003cem\u003esee Tables\u0026nbsp;1 and 3\u003c/em\u003e) indicate FB detected ISUP-GGs 2\u0026ndash;5 more frequently, while SB identified slightly more cases of no PCa or ISUP-GG 1 categorized as ncsPCa (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Nonetheless, these results also indicate that SB detected a higher ISUP-GG in a notable proportion of patients, which could impact prognostic accuracy and treatment recommandations if only FB had been used. Such misclassification would be particularly problematic if a csPCa was completely overlooked, and the patient was incorrectly assigned an ISUP-GG 0. This could lead to false reassurance and delayed follow-up. Similarly, underestimating a higher ISUP-GG might result in missing the need for a more aggressive treatment, particularly in rapidly progressing, aggressive PCa cases where an active surveillance (AS) approach might otherwise be recommended. A limitation of this study is the inclusion of biopsy na\u0026iuml;ve patients and active surveillance patients, where prior biopsy may alter prostate anatomy, potentially affecting fusion biopsy accuracy. Furthermore, the biopsies were performed by fourteen different urology specialists, ranging from residents to specialists with over 10 years\u0026rsquo; experience in the field.\u003c/p\u003e \u003cp\u003eOur results align with previous studies. Ahdoot et al. (n\u0026thinsp;=\u0026thinsp;2103;2020) found a significantly higher detection rate for ISUP-GG 3\u0026ndash;5 with FB, while SB still identified a considerable number of PCa cases across all ISUP-GGs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Studies by Plousard et al. (2019), Dorfinger et al. (2022), and Kasivisvanathan et al. (2018) support the combination of both methods to improve csPCa detection [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, Kasivisvanathan et al. showed that ISUP-GG 1 PCa was detected more than twice as often with SB, these results also correspond with the study carried out by Kaufmann et al. (2022) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similarly, Siddiqui et al. (2015) reported increased csPCa detection with FB and fewer ncsPCa cases, while in the study conducted by Mortezavi et al. (2018) SB outperformed FB due to a high number of false negative cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In a recent study by Dagnino et al. (2024) the authors show promising results with the use of combining microultrasound (micro-US) and mpMRI with the potential of avoiding unnecessary SB [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Economic analysis of biopsy methods is an important factor in clinical practice, considering the cost-effectiveness. A recent systematic review conducted by Llewellyn et al. in 2024 evaluated the cost-effectiveness of software fusion biopsy technologies compared to cognitive fusion biopsies and further assessment whether concomitant systematic biopsy influences cost-effectiveness [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The study suggests that software fusion might be worth the additional cost, but since its diagnostic superiority over cognitive fusion is uncertain, the economic conclusions are weaker. Noujeim et al. (2023) proposed perilesional biopsy as a possible alternative to the combined FB/SB with comparable detection rates [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In clinical practice, SB remains crucial as it identifies csPCa cases missed by FB, aiding treatment decisions such as nerve-sparing surgery or radical prostatectomy. A significant factor influencing diagnostic accuracy of mpMRI is the variability in the positive predictive value (PPV), particularly for PI-RADS 3 lesions as stated by Mazzone et al. (2021), reinforcing SB\u0026acute;s role in detection [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Considering this, this could be a potential influencing factor for our study as we included patients with PIRADS 3, thus adding more value to the systematic approach for detection of PCa. All mpMRI images in this study were double read by two radiologists prior to fusion biopsy. Meaning, the prior given PIRADS score was upgraded or downgraded according to the expertise of the second radiologist with over 10 years of experience with prostate MRI. The prior given results may be a potential factor for inter-reader variability.\u003c/p\u003e \u003cp\u003eRegarding access routes, our study demonstrated a significantly higher csPCa detection rates with TP approach. This is consistent with Ber et al. (n\u0026thinsp;=\u0026thinsp;77; 2020) and Zattoni et al. (n\u0026thinsp;=\u0026thinsp;5241; 2022), who found a higher csPCa detection using TP approach [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In a more recent study conducted by Liu et. al (2024), the results of the study reported superior overall detection rate with TP biopsy but significant difference in detecting csPCa, further no benefit was noted with additional target biopsy after systematic biopsy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. El-Achar et. al (2022) and Kaneko et. al (2023) found that TP biopsies resulted in larger core samples and fewer complications [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Systematic reviews by Rai et al. (2021) and Paesano et al. (2023) further support TP\u0026acute;s superiority, particularly for anterior tumors and lower infection risks [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. While prior reviews did not establish TP as superior, recently conducted studies with larger cohorts have confirmed its advantages, leading the EAU to recommend TP since 2022 [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. A limiting factor in our study was the differences in PSA-density between TP and TR groups, which may influence predictive power. However, the observed difference (0.028 ng/mL/ccm) is clinically negligible, as patients with PSA-density\u0026thinsp;\u0026gt;\u0026thinsp;0.20 ng/mL/ccm are categorized as high risk for the risk-adapted biopsy decision [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, we have demonstrated with this study that FB detected higher ISUP-GG values than SB when both methods were performed in the same session. FB was also superior in detecting csPCa. SB slightly outperformed FB in regard to detection of non-significant PCa. However, FB should not be used as a standalone method, as it could miss or downgrade some csPCa cases compared to additional SB in a non-negligible proportion of patients. Additionally, the study showed statistically significant difference in detecting csPCa when comparing the access routes and therefore TP should be preferred, further adding to a lower risk of possibly associated complications. Further research is needed to explore the causes of missed detections or misclassifications with FB, especially regarding discordances between methods. Future studies incorporating AI in the evaluation of MRI images may help improve FB accuracy and potentially allow FB to be used as a standalone method.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMRI-US: Magnetic Resonance Imaging-Ultrasound\u003c/p\u003e\n\u003cp\u003eFB: Fusion Biopsy\u003c/p\u003e\n\u003cp\u003eSB: Systematic Biopsy\u003c/p\u003e\n\u003cp\u003ecsPCa: Clinically Significant Prostate Cancer\u003c/p\u003e\n\u003cp\u003eTP: Transperineal\u003c/p\u003e\n\u003cp\u003eTR: Transrectal\u003c/p\u003e\n\u003cp\u003empMRI: multiparametric Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eISUP-GG: International Society of Urological Pathology Grade Group\u003c/p\u003e\n\u003cp\u003ePSA: Prostate-Specific Antigen\u003c/p\u003e\n\u003cp\u003encsPCa: Clinically Insignificant Prostate Cancer\u003c/p\u003e\n\u003cp\u003eAS: Active Surveillance\u003c/p\u003e\n\u003cp\u003eRCT: Randomized Controlled Trial\u003c/p\u003e\n\u003cp\u003eEAU: European Association of Urology\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of University Karl Landsteiner approved this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026acute; Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA \u0026Ouml;kr\u0026ouml;si: Protocol/Project development, Data collection and management, Data analysis, Manuscript writing\u003c/p\u003e\n\u003cp\u003eA Peltzer Svarer: Data collection and management, Data analysis\u003c/p\u003e\n\u003cp\u003eG Rosta: Protocol/project development, Manuscript editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eB Wambacher: Manuscript editing\u003c/p\u003e\n\u003cp\u003eG Heinz: Protocol/project development, Manduscript editing\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerlay J, Ervik M, Lam F, et al (2024) Global Cancer Observatory: Cancer Today. 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World J Urol 37:243\u0026ndash;251. https://doi.org/10.1007/s00345-018-2399-z\u003c/li\u003e\n\u003cli\u003eSiddiqui MM, Rais-Bahrami S, Turkbey B, et al (2015) Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA 313:390\u0026ndash;7. https://doi.org/10.1001/jama.2014.17942\u003c/li\u003e\n\u003cli\u003eDorfinger J, Ponholzer A, Stolzlechner M, et al (2022) MRI/ultrasound fusion biopsy of the prostate compared to systematic prostate biopsy \u0026ndash; Effectiveness and accuracy of a combined approach in daily clinical practice. Eur J Radiol 154:110432. https://doi.org/10.1016/j.ejrad.2022.110432\u003c/li\u003e\n\u003cli\u003eZattoni F, Marra G, Kasivisvanathan V, et al (2022) The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study. J Urol 208:830\u0026ndash;837. https://doi.org/10.1097/JU.0000000000002802\u003c/li\u003e\n\u003cli\u003eKasivisvanathan V, Rannikko AS, Borghi M, et al (2018) MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med 378:1767\u0026ndash;1777. https://doi.org/10.1056/NEJMoa1801993\u003c/li\u003e\n\u003cli\u003eKaufmann B, Saba K, Schmidli TS, et al (2022) Prostate cancer detection rate in men undergoing transperineal template-guided saturation and targeted prostate biopsy. Prostate 82:388\u0026ndash;396. https://doi.org/10.1002/pros.24286\u003c/li\u003e\n\u003cli\u003eMortezavi A, M\u0026auml;rzendorfer O, Donati OF, et al (2018) Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer. J Urol 200:309\u0026ndash;318. https://doi.org/10.1016/j.juro.2018.02.067\u003c/li\u003e\n\u003cli\u003eDagnino F, Avolio PP, Fasulo V, et al (2024) Clinically significant prostate cancer detection rate in biopsy-na\u0026iuml;ve patients with mpMRI and microultrasound topographically discordant lesions: A single-center retrospective analysis. Urol Oncol 42:447.e11-447.e16. https://doi.org/10.1016/j.urolonc.2024.06.021\u003c/li\u003e\n\u003cli\u003eLlewellyn A, Phung TH, O Soares M, et al (2024) MRI software and cognitive fusion biopsies in people with suspected prostate cancer: a systematic review, network meta-analysis and cost-effectiveness analysis. Health Technol Assess 28:1\u0026ndash;310. https://doi.org/10.3310/PLFG4210\u003c/li\u003e\n\u003cli\u003eNoujeim J-P, Belahsen Y, Lefebvre Y, et al (2023) Optimizing multiparametric magnetic resonance imaging-targeted biopsy and detection of clinically significant prostate cancer: the role of perilesional sampling. Prostate Cancer Prostatic Dis 26:575\u0026ndash;580. https://doi.org/10.1038/s41391-022-00620-8\u003c/li\u003e\n\u003cli\u003eMazzone E, Stabile A, Pellegrino F, et al (2021) Positive Predictive Value of Prostate Imaging Reporting and Data System Version 2 for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol Oncol 4:697\u0026ndash;713. https://doi.org/10.1016/j.euo.2020.12.004\u003c/li\u003e\n\u003cli\u003eBer Y, Segal N, Tamir S, et al (2020) A noninferiority within-person study comparing the accuracy of transperineal to transrectal MRI-US fusion biopsy for prostate-cancer detection. Prostate Cancer Prostatic Dis 23:449\u0026ndash;456. https://doi.org/10.1038/s41391-020-0205-7\u003c/li\u003e\n\u003cli\u003eZattoni F, Marra G, Kasivisvanathan V, et al (2022) The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study. J Urol 208:830\u0026ndash;837. https://doi.org/10.1097/JU.0000000000002802\u003c/li\u003e\n\u003cli\u003eLiu J-X, Wang Z-Y, Niu S-X, et al (2024) Transrectal versus transperineal prostate biopsy for cancer detection in patients with gray-zone prostate-specific antigen: a multicenter, real-world study. Asian J Androl 26:377\u0026ndash;381. https://doi.org/10.4103/aja20241\u003c/li\u003e\n\u003cli\u003eEl-Achkar A, Abou Heidar N, Labban M, et al (2022) MRI/US fusion transperineal versus transrectral biopsy of prostate cancer: Outcomes and complication rates, a tertiary medical center experience in the Middle East. Turk J Urol 48:98\u0026ndash;105. https://doi.org/10.5152/tud.2022.21248\u003c/li\u003e\n\u003cli\u003eKaneko M, Medina LG, Lenon MSL, et al (2023) Transperineal vs transrectal magnetic resonance and ultrasound image fusion prostate biopsy: a pair-matched comparison. Sci Rep 13:13457. https://doi.org/10.1038/s41598-023-40371-7\u003c/li\u003e\n\u003cli\u003eRai BP, Mayerhofer C, Somani BK, et al (2021) Magnetic Resonance Imaging/Ultrasound Fusion-guided Transperineal Versus Magnetic Resonance Imaging/Ultrasound Fusion-guided Transrectal Prostate Biopsy-A Systematic Review. Eur Urol Oncol 4:904\u0026ndash;913. https://doi.org/10.1016/j.euo.2020.12.012\u003c/li\u003e\n\u003cli\u003ePaesano N, Catal\u0026aacute; V, Tcholakian L, et al (2023) A Systematic Review of the Current Status of Magnetic Resonance-Ultrasound Images Fusion Software Platforms for Transperineal Prostate Biopsies. Cancers (Basel) 15:. https://doi.org/10.3390/cancers15133329\u003c/li\u003e\n\u003cli\u003eXiang J, Yan H, Li J, et al (2019) Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis. World J Surg Oncol 17:31. https://doi.org/10.1186/s12957-019-1573-0\u003c/li\u003e\n\u003cli\u003eLoy LM, Lim GH, Leow JJ, et al (2020) A systematic review and meta-analysis of magnetic resonance imaging and ultrasound guided fusion biopsy of prostate for cancer detection-Comparing transrectal with transperineal approaches. Urol Oncol 38:650\u0026ndash;660. https://doi.org/10.1016/j.urolonc.2020.04.005\u003c/li\u003e\n\u003cli\u003eEAU Guidelines Edn. presented at the EAU Annual Congress Paris 2024. ISBN 978-94-92671-23-3\u003c/li\u003e\n\u003cli\u003eSchoots IG, Padhani AR (2021) Risk-adapted biopsy decision based on prostate magnetic resonance imaging and prostate-specific antigen density for enhanced biopsy avoidance in first prostate cancer diagnostic evaluation. BJU Int 127:175\u0026ndash;178. https://doi.org/10.1111/bju.15277\u003c/li\u003e\n\u003cli\u003eStevens E, Truong M, Bullen JA, et al (2020) Clinical utility of PSAD combined with PI-RADS category for the detection of clinically significant prostate cancer. Urologic Oncology: Seminars and Original Investigations 38:846.e9-846.e16. https://doi.org/10.1016/j.urolonc.2020.05.024\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1-5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cancer of prostate, Image-Guided biopsy, Transrectal approach, Transperineal approach, Clinical significance","lastPublishedDoi":"10.21203/rs.3.rs-6466948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6466948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003eThis study aims to evaluate whether MRI-US-guided FB leads to improved diagnostic accuracy compared to SB in detecting csPCa, further assessing whether the TP or TR biopsy approach influences outcomes.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective, single-center analysis was performed on 851 (Median age 70) patients who underwent combined FB and SB when PIRADS 3 or higher was indicated on mpMRI between June 2019 and November 2024. The highest ISUP-GG was compared between the two biopsy methods with analysis of discordant findings between the methods. Furthermore, the detection rates of csPCa were compared between the TP and TR access routes.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eFB identified higher ISUP GG in 70.97% of discordant cases, with FB detecting csPCa in 42.2%of patients compared to 28.5% by SB (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Insignificant PCa was detected with similar frequency by both methods, with a close majority for the SB (30.3%) vs. FB (28.2%). Statistically significant association in csPCa detection rates was found between TP (50.1%) and TR (43.0%) approaches (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eFB significantly improves the detection of higher ISUP GG and csPCa compared to SB. However, the use of both methods together provides the most reliable diagnosis.\u003c/p\u003e","manuscriptTitle":"Is MRI/US-guided fusion biopsy ready to replace systematic biopsy in detecting clinically significant prostate carcinoma? – A retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 08:40:46","doi":"10.21203/rs.3.rs-6466948/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6935390-4aec-4760-beca-3229088abd40","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-22T13:23:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 08:40:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6466948","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6466948","identity":"rs-6466948","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}