Preoperative Local Staging of Prostate Cancer: Comparison of mpMRI and PSMA PET/CT Against Radical Prostatectomy Histopathology

Preoperative Local Staging of Prostate Cancer: Comparison of mpMRI and PSMA PET/CT Against Radical Prostatectomy Histopathology | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Preoperative Local Staging of Prostate Cancer: Comparison of mpMRI and PSMA PET/CT Against Radical Prostatectomy Histopathology Oleksii Pisotskyi, Piotr Petrasz, Piotr Zorga, Paweł Szponar, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9141498/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Accurate assessment of local tumour stage (T stage) is essential for selecting optimal treatment in patients with prostate cancer. Multiparametric MRI (mpMRI) is currently the reference imaging modality for local staging, while PSMA PET/CT has emerged as a highly sensitive technique for nodal and distant disease. However, its role in evaluating local tumour extent remains unclear. The aim of this prospective study was to compare the accuracy of mpMRI and PSMA PET/CT in preoperative T staging using radical prostatectomy histopathology as the reference standard. Results: A total of 128 patients with biopsy-proven prostate cancer underwent both mpMRI and PSMA PET/CT before treatment. In a subgroup of 51 patients treated with radical prostatectomy, histopathology confirmed ≥pT3 disease in 25 patients (49%), including 20 cases of pT3a and 5 of pT3b. MpMRI correctly identified the pathological T stage in 17 patients (33%), whereas PSMA PET/CT was concordant in 13 patients (26%). Both modalities matched histopathology in 7 cases (14%). MpMRI overstaged disease in 10% of patients and understaged in 57%, while PSMA PET/CT overstaged in 8% and understaged in 67%. For detection of ≥pT3 disease, mpMRI demonstrated a sensitivity of 68% and specificity of 88.5%, compared with 52% and 92.3% for PSMA PET/CT, respectively. MpMRI showed higher sensitivity for detecting extraprostatic extension (70% vs 25%), whereas PSMA PET/CT demonstrated comparable or slightly higher performance for seminal vesicle invasion (80% vs 60%). Conclusions: MpMRI demonstrated higher sensitivity and overall concordance with histopathology in the assessment of local tumour stage, particularly for extraprostatic extension. PSMA PET/CT showed higher specificity but tended to underestimate local disease extent. These findings support mpMRI as the primary imaging modality for local staging, while PSMA PET/CT should be considered a complementary tool, particularly in the context of combined local and systemic staging. Figures Figure 1 Figure 2 Figure 3 1. Introduction Prostate cancer remains one of the most common malignancies in men and a leading cause of cancer-related mortality worldwide ( 1 ). Treatment decisions in localized and locally advanced disease rely heavily on accurate staging, including assessment of the primary tumour (T), regional lymph nodes (N) and distant metastases (M). Among these, correct evaluation of local tumour extent (T stage) is particularly important when considering radical prostatectomy or radiotherapy, as it influences the extent of surgery, nerve-sparing strategy and radiotherapy target volumes. Multiparametric magnetic resonance imaging (mpMRI) is currently the recommended imaging modality for local staging of prostate cancer ( 2 ). It provides high-resolution anatomical and functional information based on T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced sequences, allowing assessment of extracapsular extension (EPE, T3a) and seminal vesicle invasion (SVI, T3b). Nevertheless, mpMRI is not infallible. Both underestimation and overestimation of local stage have been reported, and performance may vary across centres depending on image quality, protocol standardisation and, importantly, reader expertise ( 3 ). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has rapidly gained importance in prostate cancer imaging ( 4 ). PSMA is a type II transmembrane glycoprotein markedly overexpressed in prostate cancer cells, in both primary lesions and metastases ( 5 ). Radiolabelled PSMA ligands, such as 68Ga-PSMA-11 or 18F-labelled tracers, enable highly sensitive and specific whole-body imaging of prostate cancer, with excellent performance in detecting nodal and distant metastases ( 6 ). The role of PSMA PET/CT in local T staging, however, is less clear. Many studies demonstrate its superiority over conventional imaging (CT, bone scintigraphy) for N and M staging, and promising results have also been reported for intraprostatic tumour localization ( 7 ), ( 8 ). Still, its ability to reliably assess extracapsular extension and seminal vesicle invasion remains controversial. Some data suggest that mpMRI provides better discrimination of EPE and SVI, while PSMA PET/CT may better depict the dominant intraprostatic lesion or advanced extra-prostatic spread ( 9 ), ( 10 ). Given the increasing use of PSMA PET/CT at the primary staging of prostate cancer, clinicians face a practical question: can PSMA PET/CT replace mpMRI in local staging, or should it be considered complementary? To address this question, robust head-to-head comparisons against histopathological reference are needed. The aim of the present study was therefore to compare the preoperative assessment of T stage provided by mpMRI and PSMA PET/CT in patients with prostate cancer undergoing radical prostatectomy, using final histopathology as the reference standard. Particular emphasis was placed on detection of ≥pT3 disease, including extracapsular extension (T3a) and seminal vesicle invasion (T3b). 2. Materials and Methods 2.1 Study design and patient population This was a prospective single-centre study including 128 consecutive patients with biopsy-proven prostate cancer who underwent PSMA PET/CT and conventional imaging (mpMRI, CT, bone scintigraphy) as part of primary staging. For the present analysis, we focused on a predefined subgroup of 51 patients who subsequently underwent robot-assisted radical prostatectomy (RARP) with available detailed histopathological assessment. In this subgroup, preoperative T stage determined by mpMRI and PSMA PET/CT was directly compared with the final pathological T stage. A flowchart of patient inclusion and exclusion is shown in Fig. 1 . Inclusion criteria for the overall cohort comprised histologically confirmed adenocarcinoma of the prostate, availability of pre-treatment mpMRI and PSMA PET/CT, and absence of prior definitive therapy, including surgery, radiotherapy or androgen deprivation therapy. For the histopathology-referenced subgroup, additional eligibility criteria included performance of radical prostatectomy after imaging and availability of a complete pathology report with pT stage assigned according to the TNM classification. Basic clinical characteristics of the whole cohort (n = 128) have been described in detail in the original study; the mean age was 67.2 years, median PSA 12 ng/mL, and the majority of patients had intermediate- or high-risk disease. These characteristics are summarised in Table 1 The study was approved by the local ethics committee, and all patients provided written informed consent. 2.2 Imaging protocols 2.2.1 Multiparametric MRI All patients underwent mpMRI of the prostate prior to definitive treatment. Examinations were performed using a high-field MRI scanner with a pelvic phased-array coil. The standard protocol included: The standard imaging protocol consisted of high-resolution T2-weighted sequences acquired in axial, sagittal and coronal planes, diffusion-weighted imaging with generation of apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced imaging following intravenous administration of gadolinium-based contrast agent. Images were interpreted by experienced radiologists according to current recommendations, with assessment of tumour location, presence of extracapsular extension (EPE) and seminal vesicle invasion (SVI). T stage was assigned following the TNM classification. 2.2.2 PSMA PET/CT PSMA PET/CT was performed using a dedicated PET/CT system after intravenous injection of a PSMA-targeted radiotracer (most commonly 68Ga-PSMA-11). Whole-body acquisition from the skull base to mid-thigh was obtained 60–90 minutes after injection. A low-dose CT scan was used for attenuation correction and anatomical correlation. Images were interpreted by nuclear medicine physicians aware of clinical data and MRI findings. The primary intraprostatic lesion, potential extracapsular extension and seminal vesicle invasion were evaluated visually on PET and fusion PET/CT images. T stage was assigned according to TNM, using a combination of uptake extent and anatomical information from CT. 2.3 Histopathological assessment All 51 patients in the analysed subgroup underwent robot-assisted radical prostatectomy. The prostate gland, seminal vesicles and, when available, lymph nodes were examined by dedicated genitourinary pathologists. T stage was assigned according to the TNM system: Pathological T stage was assigned according to the TNM classification. Organ-confined disease was defined as pT2 (T2a–T2c), extraprostatic extension without seminal vesicle invasion as pT3a, and seminal vesicle invasion as pT3b. For the purpose of the present analysis, locally advanced disease was defined as ≥pT3, encompassing both pT3a and pT3b. 2.4 Definition of concordance, over- and understaging For each modality (mpMRI, PSMA PET/CT), T stage as reported in the clinical imaging report was compared with the final pT stage. Concordance was defined as identical T category between imaging and histopathology. Overstaging (upstaging) was defined as assignment of a higher T category on imaging than on histopathology; understaging (downstaging) as assignment of a lower T category. 2.5 Statistical analysis The primary endpoint was the concordance rate of mpMRI and PSMA PET/CT with histopathological T stage in the 51-patient prostatectomy subgroup. Secondary endpoints included the rates of over- and understaging for each modality, diagnostic performance parameters for detection of ≥pT3 disease (including sensitivity, specificity, true positive, false negative, true negative and false positive values), and separate analyses of detection rates for pT3a (EPE) and pT3b (SVI). Continuous variables are presented as means or medians with appropriate measures of dispersion; categorical variables as counts and percentages. Differences in T-stage distributions between modalities were assessed using the chi-squared test. Diagnostic performance measures (sensitivity, specificity) were calculated in relation to histopathology. A p-value < 0.05 was considered statistically significant. 3. Results 3.1 Distribution of histopathological T stage Among the 51 patients who underwent radical prostatectomy, histopathological examination demonstrated organ-confined disease (pT1c–pT2c) in 26 patients (51%), extraprostatic extension (pT3a) in 20 patients (39%), and seminal vesicle invasion (pT3b) in 5 patients (10%). Overall, locally advanced disease (≥ pT3) was confirmed in 25 of 51 patients (49%). Within the locally advanced subgroup, extraprostatic extension (pT3a) accounted for the majority of cases (20/25; 80%), whereas seminal vesicle invasion (pT3b) was less frequent (5/25; 20%). The distribution of pathological T stages therefore demonstrated a relatively balanced proportion between organ-confined and locally advanced disease in the operated cohort. 3.2 Concordance of mpMRI and PSMA PET/CT with histopathology This analysis compared T-stage classification on mpMRI and PSMA PET/CT with final histopathological results in 51 patients who underwent radical prostatectomy. The distribution of T categories across modalities is presented in Fig. 2 and Table 2. MpMRI correctly classified the T stage in 17 of 51 patients (33%), whereas PSMA PET/CT was concordant with histopathology in 13 patients (26%). In 7 patients (14%), both imaging modalities simultaneously matched the pathological T stage. In 28 patients (55%), neither modality achieved exact concordance. Within the discordant subgroup, imaging findings differed from histopathology by only one T category in 18 cases (64%). MpMRI was closer to the pathological stage in 4 cases (14%), whereas PSMA PET/CT was closer in 6 cases (21%). Overall, at least one imaging modality correctly identified the pathological T stage in 23 of 51 patients (45%). Category-level comparison demonstrated discrepancies particularly within the T2b group. MpMRI classified 18 patients as T2b and PSMA PET/CT classified 28 patients as T2b, whereas histopathology confirmed 4 cases in this category.In the T3a category, mpMRI identified 14 cases and PSMA PET/CT identified 5 cases, while histopathology demonstrated 20 cases. Lower concordance was also observed in T1c and T2a categories, which were infrequent in histopathology but more frequently assigned by imaging modalities. 3.3 Over- and understaging relative to histopathology In this analysis, imaging-based T-stage classification on mpMRI and PSMA PET/CT was compared with final histopathological results in 51 patients who underwent radical prostatectomy. Exact concordance with histopathology was observed in 17 patients (33%) for mpMRI and in 13 patients (26%) for PSMA PET/CT. In seven cases (14%), both imaging modalities were concordant with the pathological T stage. In 28 patients (55%), neither modality showed exact agreement with histopathology. Within this subgroup, imaging results differed from the pathological stage by one T category in 18 cases (64%). MpMRI was closer to the pathological stage in 4 cases (14%), whereas PSMA PET/CT was closer in 6 cases (21%). Overall, at least one imaging modality correctly classified the pathological T stage in 23 patients (45%). The distribution of overstaging and understaging is presented in Table 3. For mpMRI, overstaging occurred in 5 of 51 patients (10%), while understaging was observed in 29 patients (57%). For PSMA PET/CT, overstaging occurred in 4 patients (8%) and understaging in 34 patients (67%). Understaging was more frequent than overstaging for both imaging modalities. 3.4 Sensitivity and specificity relative to histopathology For the purpose of analysing clinically relevant locally advanced disease, pT3a and pT3b cases were combined and analysed as “≥pT3”. In the subgroup of 51 patients who underwent radical prostatectomy, histopathology confirmed ≥pT3 disease in 25 patients, while 26 patients had organ-confined disease (≤ pT2). Based on imaging results, true and false classifications relative to histopathology were determined. For mpMRI, 17 true positives (TP), 8 false negatives (FN), 23 true negatives (TN) and 3 false positives (FP) were recorded. For PSMA PET/CT, 13 TP, 12 FN, 24 TN and 2 FP were observed. These data are summarised in Table 4. Sensitivity and specificity were calculated for both modalities (Table 5, Fig. 3 ). For mpMRI, sensitivity was 68% and specificity was 88.5%. For PSMA PET/CT, sensitivity was 52% and specificity was 92.3%. In addition to sensitivity and specificity, positive and negative predictive values were calculated. For mpMRI, the positive predictive value (PPV) was 85% and the negative predictive value (NPV) was 74.2%. For PSMA PET/CT, PPV was 86.7% and NPV was 66.7%. Ninety-five percent confidence intervals (CI) for sensitivity were 47–85% for mpMRI and 31–72% for PSMA PET/CT, reflecting the limited sample size of the prostatectomy subgroup. Comparative analysis using the McNemar test did not demonstrate a statistically significant difference between the two modalities in detecting ≥pT3 disease (p > 0.05). 3.5 Detection of pT3a (extraprostatic extension) and pT3b (seminal vesicle invasion) To assess the performance of both imaging modalities in specific components of locally advanced disease, pT3a (extracapsular extension, EPE) and pT3b (seminal vesicle invasion, SVI) were analysed separately. Histopathology identified 20 cases of pT3a and 5 cases of pT3b in the prostatectomy cohort (Table 6). For pT3a, mpMRI identified 14 of 20 cases, corresponding to a sensitivity of 70%, while PSMA PET/CT identified 5 of 20 cases (sensitivity 25%). For pT3b, mpMRI identified 3 of 5 cases (sensitivity 60%), whereas PSMA PET/CT identified 4 of 5 cases (sensitivity 80%). 4. Discussion In this prospective single-centre study, we performed a direct comparison of mpMRI and PSMA PET/CT for preoperative local staging of prostate cancer, using radical prostatectomy histopathology as the reference standard. Several clinically relevant observations emerge from our analysis. MpMRI achieved higher overall concordance with histopathological T stage than PSMA PET/CT (33% vs. 26%). Both imaging modalities more frequently underestimated rather than overestimated local tumour extent, with understaging observed in 57% of cases for mpMRI and 67% for PSMA PET/CT. In the assessment of clinically significant locally advanced disease (≥ pT3), mpMRI demonstrated higher sensitivity (68% vs. 52%), whereas PSMA PET/CT showed slightly higher specificity (92.3% vs. 88.5%). When analysed separately, mpMRI was more sensitive in detecting extraprostatic extension (pT3a), while PSMA PET/CT demonstrated comparable performance in identifying seminal vesicle invasion (pT3b). Taken together, these findings suggest that mpMRI remains more reliable for detailed evaluation of capsular integrity and early extracapsular spread, whereas PSMA PET/CT may provide complementary information, particularly in cases of more advanced local disease. 4.1 Comparison with previous studies The superiority of mpMRI over PSMA PET/CT in accurately determining T stage in our cohort aligns with several prior studies evaluating local staging performance. Many reports suggest that mpMRI — owing to its high anatomical resolution and established radiologic criteria for EPE and SVI — remains the most reliable modality for detailed assessment of the prostate capsule and periprostatic tissues ( 11 ), ( 12 ). A recent retrospective study evaluated the diagnostic performance of mpMRI and 68Ga-PSMA PET/CT in 49 patients who underwent both modalities prior to radical prostatectomy ( 13 ). Using a 12-sector prostate map interpreted by uroradiologists, nuclear medicine physicians and pathologists, the authors compared intraprostatic tumour localisation and locoregional staging against whole-mount histopathology. Of 362 tumour-positive sectors, mpMRI identified 174 and PSMA PET/CT identified 175, with both modalities showing comparable accuracy for index-lesion localisation (AUC 0.69 vs. 0.66; p = 0.82), and similar sensitivity and specificity profiles. MpMRI demonstrated significantly greater accuracy for detecting extracapsular extension (AUC 0.80 vs. 0.57; p = 0.027), while PSMA PET/CT and mpMRI performed similarly in identifying seminal vesicle invasion, bladder neck invasion and lymph node involvement. The authors concluded that mpMRI remains the preferred modality for assessing extracapsular disease, particularly when planning nerve-sparing surgery in high-risk patients, whereas both mpMRI and PSMA PET/CT provide comparable accuracy for intraprostatic tumour localisation, and PSMA PET/CT performs reliably for nodal staging. Another study involving 70 patients who underwent mpMRI, 68Ga-PSMA PET/CT and subsequent radical prostatectomy directly compared the diagnostic performance of each modality, as well as their combined use ( 14 ). The authors found no significant differences among mpMRI, PSMA PET/CT and the combined protocol in their ability to detect either index lesions or clinically significant prostate cancer, nor in their capacity to localize tumours within the superior, inferior, anterior, posterior, left or right halves of the gland. When postoperative pathology was used as the reference standard, mpMRI alone and mpMRI combined with PSMA PET/CT demonstrated acceptable accuracy for local T-stage assessment, whereas PSMA PET/CT consistently underestimated local tumour stage (p < 0.01). For lymph node staging, all three imaging strategies showed comparable performance, with no significant differences relative to pathological nodal status. The authors concluded that PSMA PET/CT lacks reliability for local tumour staging, and that combining PSMA PET/CT with mpMRI does not offer a diagnostic advantage over mpMRI alone for lesion detection, localization or local staging. Similar findings were reported by Sonni et al., who compared the diagnostic performance of mpMRI and 68Ga-PSMA PET/CT for T-stage assessment in 74 patients with intermediate- or high-risk prostate cancer ( 15 ). In this study, mpMRI demonstrated significantly higher accuracy in detecting extracapsular extension, with an AUC of 0.79 compared with 0.59 for PSMA PET/CT (p = 0.002). A similar advantage was observed for seminal vesicle invasion, where mpMRI achieved an AUC of 0.84 versus 0.63 for PSMA PET/CT (p = 0.001). These results clearly indicate the superiority of mpMRI over PSMA PET/CT in evaluating local tumour extent, particularly in the assessment of EPE and SVI. Further evidence supporting the advantage of mpMRI in local tumour assessment comes from a study evaluating intraprostatic lesion detection in patients undergoing HDR brachytherapy planning ( 16 ). In a cohort of 27 patients who received both mpMRI and 68Ga-PSMA PET/CT, tumour localization was assessed across 24 predefined prostate segments using histopathology from targeted biopsy as the reference standard. In segment-based ROC analysis (447 segments from 19 patients), mpMRI achieved significantly higher diagnostic accuracy than PSMA PET/CT, with AUC values of 0.770 and 0.781 for two MRI readers, compared with 0.684 and 0.608 for PET/CT (p < 0.001). Intermodality comparison similarly demonstrated superiority of mpMRI (AUC 0.815 vs. 0.690; p = 0.006). A complementary patient-based congruence analysis confirmed higher concordance of mpMRI with biopsy results (83% vs. 76%; p = 0.034), a difference that remained significant even after allowing near-adjacent agreement (96.5% vs. 92.7%; p = 0.024). Overall, this study indicates that in patients with low- and intermediate-risk prostate cancer, mpMRI provides more accurate intraprostatic lesion detection than PSMA PET/CT, although larger prospective studies are needed to validate these findings. On the other hand, several authors have found encouraging performance of PSMA PET/CT, particularly in detecting dominant intraprostatic lesions and advanced disease, sometimes reporting higher sensitivity at the patient level. A study by Berger et al. compared PSMA PET/CT and MRI with radical prostatectomy histopathology and demonstrated that PSMA PET/CT correctly identified all histologically confirmed tumour foci (100%), whereas MRI detected 94% of these lesions ( 17 ). Moreover, PSMA PET/CT showed higher sensitivity for localisation of primary intraprostatic lesions, which may be clinically relevant, particularly in patients with more advanced disease. Similarly, a meta-analysis by Zhao et al. (2022) reported that PSMA PET/CT provides significantly higher sensitivity (0.93 vs. 0.87; p < 0.01) and higher AUC values (0.91 vs. 0.84) on a per-patient basis, while mpMRI offers superior specificity for localisation of individual lesions (0.88 vs. 0.71; p < 0.05) ( 18 ).This pattern suggests that PSMA PET/CT excels in overall disease detection, whereas mpMRI maintains advantages in detailed anatomical discrimination at the lesion level. In a study by Yi Yi Li et al. involving 115 patients, PSMA PET/CT demonstrated higher diagnostic specificity than MRI, particularly among individuals with PSA levels between 4 and 20 ng/mL ( 19 ). Furthermore, SUVmax values showed a significant correlation with tumour aggressiveness (Gleason score), highlighting the potential role of PSMA PET/CT as a prognostic imaging biomarker. Our findings align with this heterogeneous body of evidence. In our cohort, PSMA PET/CT frequently underestimated the true extent of local tumour spread, particularly in cases of subtle or early extracapsular extension. This pattern is biologically plausible: PSMA PET/CT depicts radiotracer uptake and tumour metabolism rather than the precise anatomical integrity of the prostatic capsule. Minimal capsular irregularities or microscopic extension beyond the gland may therefore remain below the detection threshold. In contrast, mpMRI provides high-resolution morphological detail and well-established indirect markers of early EPE — such as capsular bulging, neurovascular bundle asymmetry or obliteration of the rectoprostatic angle — which likely explains its superior sensitivity for detecting pT3a disease. 4.2 Clinical implications of under- and overstaging Both understaging and overstaging may have meaningful clinical consequences in the management of prostate cancer. Underestimation of local tumour extent risks inappropriate selection of nerve-sparing radical prostatectomy in patients with true ≥pT3 disease, potentially leading to positive surgical margins or incomplete resection. Similarly, it may result in insufficient radiotherapy coverage. Conversely, overstaging may lead to unnecessarily aggressive surgical dissection or exclude patients who could otherwise be candidates for active surveillance or organ-preserving approaches. A recent study assessing the concordance between mpMRI-based clinical staging (rT) and final pathological staging (pT) in patients with high-risk prostate cancer provides additional insight into the clinical consequences of staging inaccuracies ( 20 ). In this cohort, mpMRI demonstrated a concordance rate of 66.4% and detected extraprostatic extension (≥ pT3) with a sensitivity of 65.1% and an overall accuracy of 67.5%. Importantly, the authors emphasised that radiologic suspicion of ≥rT3 should not automatically preclude nerve-sparing prostatectomy. Among patients with ≥rT3 disease, 84.5% still underwent primary nerve-sparing surgery supported by the intraoperative frozen section technique (IFST), which allowed at least unilateral nerve preservation in 94.7% of cases, with a very low IFST-related positive surgical margin rate of 1.8%. These findings highlight two key points: first, mpMRI retains limitations in correctly identifying extraprostatic disease, and second, overstaging on mpMRI does not necessarily mandate abandoning nerve-sparing strategies when intraoperative verification is available. This reinforces the notion that both under- and overstaging have practical implications and that a tailored intraoperative assessment may help mitigate the risks associated with imaging inaccuracies. Additional evidence regarding the clinical implications of staging inaccuracy comes from the study by Druskin et al., which evaluated the impact of preoperative prostate MRI on nerve-sparing decisions and positive surgical margin rates in men undergoing radical prostatectomy ( 21 ). In a matched comparison of 176 MRI-staged patients versus non-imaged controls, the rates of nonfocal extracapsular extension on final pathology were similar between groups, and MRI did not significantly reduce the overall rate of positive surgical margins (13.7% vs. 19.3%; p = 0.14). Among patients with MRI findings suspicious for nonfocal extracapsular extension, the positive margin rate was higher (20.4% vs. 11.3%), and these patients underwent nerve sparing significantly less frequently, although these differences did not reach statistical significance. The authors noted that MRI findings suggesting locally advanced disease often led surgeons to adopt a more conservative intraoperative strategy, yet this did not consistently translate into improved margin status. The study underscores that while MRI can influence surgical planning—particularly the decision to limit nerve preservation—it may not reliably prevent positive margins, especially in patients with subtle or nonfocal extracapsular extension. These findings highlight the complex relationship between imaging-based staging, intraoperative strategy, and pathological outcomes, and illustrate how both over- and understaging may directly affect functional and oncological results. In our cohort, understaging was more common than overstaging for both imaging modalities, with PSMA PET/CT demonstrating a particularly strong tendency to underestimate the true extent of local disease (67% of cases). This pattern further reinforces concerns raised in previous studies and highlights that PSMA PET/CT alone may be insufficient for surgical planning when the primary focus is accurate evaluation of capsular involvement. MpMRI, although not free from limitations, provided a more favourable balance between sensitivity and specificity and therefore offered more dependable preoperative guidance for identifying patients at risk of ≥pT3 disease. 4.3 Detection of pT3a vs. pT3b: complementary strengths The distinction between pT3a and pT3b is clinically relevant, as these entities differ in biological behaviour and surgical implications. In our subgroup analysis, mpMRI demonstrated higher sensitivity for the detection of extraprostatic extension, identifying 14 of 20 histopathologically confirmed pT3a cases (70%), compared with 5 of 20 cases detected by PSMA PET/CT (25%). This finding is consistent with the established role of mpMRI in assessing capsular integrity and periprostatic anatomy. In contrast, for seminal vesicle invasion (pT3b), PSMA PET/CT detected 4 of 5 cases (80%), whereas mpMRI identified 3 of 5 cases (60%). Although the number of pT3b cases in our cohort was limited, these results suggest that PSMA PET/CT may perform comparably to mpMRI in the assessment of seminal vesicle involvement. Taken together, the differential performance observed for pT3a and pT3b indicates that the diagnostic strengths of mpMRI and PSMA PET/CT are not identical. MpMRI appears to be more sensitive for early extracapsular extension, while PSMA PET/CT may provide complementary information in cases of suspected seminal vesicle invasion. 4.4 Strengths and limitations The present study has several strengths. It was designed as a prospective single-centre investigation and utilised radical prostatectomy histopathology as the reference standard for T-stage assessment. The analysed cohort consisted predominantly of patients with intermediate- and high-risk disease, reflecting a clinically relevant population in whom accurate local staging is particularly important. Furthermore, both imaging modalities were performed preoperatively within routine clinical workflows, which enhances the real-world applicability of the results. Certain limitations should also be considered. The prostatectomy subgroup was relatively small (n = 51), which limits the statistical power of subgroup analyses, especially for pT3b. The single-centre design may reflect institution-specific expertise in mpMRI and PSMA PET/CT interpretation and may therefore restrict generalisability. In addition, T-stage assessment was performed on a whole-gland basis, without lesion-level or sector-based correlation with whole-mount histopathology. Interobserver variability was not formally evaluated, as imaging reports were based on routine clinical interpretation. Despite these limitations, the overall consistency of our findings with previously published data supports the robustness of the observed patterns. 4.5 Future directions Future research should include larger multicentre cohorts with standardised imaging protocols, blinded interpretation and systematic whole-mount histopathological correlation. Such study designs would allow more precise evaluation of the complementary roles of mpMRI and PSMA PET/CT in local T-stage assessment. Hybrid imaging techniques, particularly PSMA PET/MRI, represent a potential avenue for integrating molecular and anatomical information within a single examination. In addition, quantitative imaging parameters—including PET-derived SUV metrics and MRI-based morphological or radiomic features—may support the development of predictive models for extracapsular extension and seminal vesicle invasion. Recent work has explored practical strategies for combining mpMRI and PSMA PET/CT findings to improve detection of extraprostatic extension ( 22 ). In a cohort of 67 patients undergoing radical prostatectomy, integration of MRI-based capsular contact length with PET-derived SUVmax improved the balance between sensitivity and specificity for EPE detection. These findings suggest that structured multimodal assessment may enhance preoperative risk stratification beyond either modality alone. Finally, the application of artificial intelligence to combined mpMRI and PSMA PET/CT datasets may further refine diagnostic accuracy, reduce interobserver variability and contribute to more individualised treatment planning. 5. Conclusions In this prospective single-centre study, mpMRI and PSMA PET/CT were directly compared for preoperative local T-stage assessment in patients undergoing radical prostatectomy, using histopathology as the reference standard. MpMRI demonstrated higher overall concordance with pathological T stage and greater sensitivity for detecting ≥pT3 disease, particularly extraprostatic extension (pT3a). PSMA PET/CT showed slightly higher specificity but a pronounced tendency toward understaging of local tumour extent. In contrast, performance for seminal vesicle invasion (pT3b) was comparable between modalities. These findings support the continued use of mpMRI as the primary imaging modality for local staging, particularly when surgical planning depends on accurate assessment of capsular involvement. PSMA PET/CT should not replace mpMRI in local T-stage evaluation but may provide complementary information, especially in patients with suspected seminal vesicle invasion or when integrated local and systemic staging is required. Further validation in larger multicentre cohorts with standardised imaging protocols and whole-mount pathological correlation is warranted to define optimal strategies for integrating mpMRI and PSMA-based imaging in preoperative staging. Abbreviations PSMA Prostate–specific membrane antigen PET/CT Positron emission tomography/computed tomography MRI Magnetic resonance imaging mpMRI Multiparametric magnetic resonance imaging CT Computed tomography SUVmax Maximum standardized uptake value PSA Prostate–specific antigen ISUP International Society of Urological Pathology TNM Tumor, Node, Metastasis classification EPE Extraprostatic extension RARP Robot–assisted radical prostatectomy Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethics Committee at the Regional Medical Chamber in Zielona Góra (approval no. 06/142/2021). All patients provided informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no specific funding for this work. Authors’ contributions OP: study design, data collection, analysis, manuscript preparation PP: study supervision, data interpretation, manuscript revision PZ: data acquisition and interpretation of imaging studies PS: data collection and patient management MG: data collection and clinical data analysis KBJ: data acquisition and data organization TD: study supervision and critical revision of the manuscript KK: data analysis and methodological support JA: study supervision, study design, and critical revision of the manuscript All authors contributed to the study, reviewed the manuscript, and approved the final version. Acknowledgements The authors would like to thank all patients who participated in this study. Authors’ information Not applicable. References Barsouk A, Padala SA, Vakiti A, Mohammed A, Saginala K, Thandra KC et al. Epidemiology, Staging and Management of Prostate Cancer. Vol. 8, Medical sciences (Basel, Switzerland). 2020. Dell’Atti L. Biparametric MRI for Local Staging of Prostate Cancer: Current Status and Future Applications. 44, Anticancer Res. 2024. Chandrasekar T, Denisenko A, Mico V, McPartland C, Shah Y, Mark JR et al. Multiparametric MRI is not sufficient for prostate cancer staging: A single institutional experience validated by a multi-institutional regional collaborative. Urologic Oncology: Seminars Original Investigations. 2023;41(8). Lenis AT, Pooli A, Lec PM, Sadun TY, Johnson DC, Lebacle C et al. 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Vol. 14, Cancers. 2022. Chow KM, So WZ, Lee HJ, Lee A, Yap DWT, Takwoingi Y et al. Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis. Vol. 84, European Urology. 2023. von Klot CAJ, Merseburger AS, Böker A, Schmuck S, Ross TL, Bengel FM et al. 68Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent, Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer. Nucl Med Mol Imaging. 2017;51(4). Lin Y, Johnson LA, Fennessy FM, Turkbey B. Prostate Cancer Local Staging with Magnetic Resonance Imaging. Volume 62. Radiologic Clinics of North America; 2024. Valentin B, Schimmöller L, Ullrich T, Klingebiel M, Demetrescu D, Sawicki LM et al. Magnetic resonance imaging improves the prediction of tumor staging in localized prostate cancer. Abdom Radiol. 2021;46(6). Triquell M, Regis L, Winkler M, Valdés N, Cuadras M, Celma A et al. Multiparametric MRI for Staging of Prostate Cancer: A Multicentric Analysis of Predictive Factors to Improve Identification of Extracapsular Extension before Radical Prostatectomy. Cancers (Basel). 2022;14(16). Ucar T, Gunduz N, Demirci E, Culpan M, Gunel H, Kir G et al. Comparison of 68Ga-PSMA PET/CT and mp-MRI in regard to local staging for prostate cancer with histopathological results: A retrospective study. Prostate. 2022;82(15). Mai Z, Zhu M, Feng T, Zhou Z, Zhou Y, Wang D et al. Comparisons of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in diagnosing prostate cancer based on tumor detection, localization and staging. World J Urol. 2024;42(1). Sonni I, Felker ER, Lenis AT, Sisk AE, Bahri S, Allen-Auerbach M et al. Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI with histopathology gold-standard in the detection, intra-prostatic localization and local extension of primary prostate cancer: results from a prospective single-center imaging trial. J Nucl Med. 2022;63(6). Moritz J, Argow S, Hupfeld SA, Schenke S, Neumann R, Damm J, Vogt, et al. Comparison of mpMRI and 68Ga-PSMA-PET/CT in the Assessment of the Primary Tumors in Predominant Low-/Intermediate-Risk Prostate Cancer. Diagnostics (Basel). 2025;15(11):1358. Berger I, Annabattula C, Lewis J, Shetty DV, Kam J, MacLean F et al. 68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: Correlation with final histopathology. Prostate Cancer Prostatic Dis. 2018;21(2). Zhao G, Ji B. Head-To-Head Comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP Bone Scintigraphy for the Detection of Bone Metastases in Patients with Prostate Cancer: A Meta-Analysis. Volume 219. American Journal of Roentgenology; 2022. Li Y, Han D, Wu P, Ren J, Ma S, Zhang J et al. Comparison of 68Ga-PSMA-617 PET/CT with mpMRI for the detection of PCa in patients with a PSA level of 4–20 ng/ml before the initial biopsy. Sci Rep. 2020;10(1). Humke C, Hoeh B, Preisser F, Wenzel M, Welte MN, Theissen L et al. Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer. Curr Oncol. 2022;29(4). Druskin SC, Liu JJ, Young A, Feng Z, Dianat SS, Ludwig WW et al. Prostate mri prior to radical prostatectomy: Effects on nerve sparing and pathological margin status. Res Rep Urol. 2017;9. Sungmin Woo D, Freedman AS, Becker D, Leithner C, Charbel, Marius E, Mayerhoefer, et al. Evaluating extraprostatic extension of prostate cancer: pragmatic integration of MRI and PSMA-PET/CT. Abdom Radiol (NY). 2025;50(11):5274–82. Tables Table 1. Baseline characteristics of the study population Clinical data Value Mean age (years) 67,2 Median age (years) 68 Age range (years) 45-82 Mean level PSA (ng/ml) 15,27 Median PSA (ng/ml) 12 PSA range (ng/ml) 1,85-55 Risk group low-risk 17 Risk group intermediate-risk 42 Risk group high-risk 69 ISUP I 32 ISUP II 31 ISUP III 22 ISUP IV 24 ISUP V 19 Table 2. Concordance of mpMRI and PSMA PET/CT with histopathology in T staging Histopathological result MRI PSMA PET/CT Matches histopathology 17 13 Both match 7 7 Remaining cases 28 28 Comparable concordance 18 18 MRI greater concordance 4 - PSMA PET/CT greater concordance - 6 Table 3. Distribution of overstaging and understaging in mpMRI and PSMA PET/CT Imaging modality Upstaging Downstaging No differences MRI 5 cases 29 cases 17 cases PSMA PET/CT 4 cases 34 cases 13 cases Table 4. True and false classifications of mpMRI and PSMA PET/CT relative to histopathology Imaging modality TP FN TN FP MRI 17 8 23 3 PSMA PET/CT 13 12 24 2 Table 5. Sensitivity and specificity of mpMRI and PSMA PET/CT Imaging modality Sensitivity (%) Specificity (%) MRI 68% 88.5% PSMA PET/CT 52% 92.3% Table 6. Detection of pT3a (EPE) and pT3b (SVI) by mpMRI and PSMA PET/CT Category Histopathology (n) MRI (n) Sensitivity MRI (%) PSMA PET/CT Sensitivity PSMA PET/CT (%) cT3a (EPE) 20 14 70 5 25 cT3b (SVI) 5 3 60 4 80 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-9141498","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":613224778,"identity":"97954541-1687-4bc9-a01b-829017e867e3","order_by":0,"name":"Oleksii 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19:54:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9141498/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9141498/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105844460,"identity":"ad66ade4-8857-4d2c-a36f-1f6a6fc2a570","added_by":"auto","created_at":"2026-03-31 17:32:57","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56275,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient selection and study design.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9141498/v1/b30c5132ee3334c6f78ea3cd.jpg"},{"id":105844458,"identity":"62c2777c-2c17-4f45-9a57-024be9888120","added_by":"auto","created_at":"2026-03-31 17:32:57","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47938,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of T stage assessed by mpMRI and PSMA PET/CT.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9141498/v1/a576acbd9366df298b9c4d73.jpg"},{"id":105844459,"identity":"84da0d1a-64ef-458f-88be-79a2e49243cf","added_by":"auto","created_at":"2026-03-31 17:32:57","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":54213,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity and specificity of mpMRI and PSMA PET/CT.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9141498/v1/e34563f63c7ac3ad6c939093.jpg"},{"id":106723606,"identity":"bea06532-4b35-41c5-8c28-fb8fff2a448e","added_by":"auto","created_at":"2026-04-12 18:08:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1139878,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9141498/v1/74886167-4d75-4a04-b540-3d3b728e82b2.pdf"}],"financialInterests":"","formattedTitle":"Preoperative Local Staging of Prostate Cancer: Comparison of mpMRI and PSMA PET/CT Against Radical Prostatectomy Histopathology","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eProstate cancer remains one of the most common malignancies in men and a leading cause of cancer-related mortality worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Treatment decisions in localized and locally advanced disease rely heavily on accurate staging, including assessment of the primary tumour (T), regional lymph nodes (N) and distant metastases (M). Among these, correct evaluation of local tumour extent (T stage) is particularly important when considering radical prostatectomy or radiotherapy, as it influences the extent of surgery, nerve-sparing strategy and radiotherapy target volumes.\u003c/p\u003e \u003cp\u003eMultiparametric magnetic resonance imaging (mpMRI) is currently the recommended imaging modality for local staging of prostate cancer (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It provides high-resolution anatomical and functional information based on T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced sequences, allowing assessment of extracapsular extension (EPE, T3a) and seminal vesicle invasion (SVI, T3b). Nevertheless, mpMRI is not infallible. Both underestimation and overestimation of local stage have been reported, and performance may vary across centres depending on image quality, protocol standardisation and, importantly, reader expertise (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eProstate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has rapidly gained importance in prostate cancer imaging (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). PSMA is a type II transmembrane glycoprotein markedly overexpressed in prostate cancer cells, in both primary lesions and metastases (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Radiolabelled PSMA ligands, such as 68Ga-PSMA-11 or 18F-labelled tracers, enable highly sensitive and specific whole-body imaging of prostate cancer, with excellent performance in detecting nodal and distant metastases (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe role of PSMA PET/CT in local T staging, however, is less clear. Many studies demonstrate its superiority over conventional imaging (CT, bone scintigraphy) for N and M staging, and promising results have also been reported for intraprostatic tumour localization (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Still, its ability to reliably assess extracapsular extension and seminal vesicle invasion remains controversial. Some data suggest that mpMRI provides better discrimination of EPE and SVI, while PSMA PET/CT may better depict the dominant intraprostatic lesion or advanced extra-prostatic spread (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven the increasing use of PSMA PET/CT at the primary staging of prostate cancer, clinicians face a practical question: \u003cb\u003ecan PSMA PET/CT replace mpMRI in local staging, or should it be considered complementary?\u003c/b\u003e To address this question, robust head-to-head comparisons against histopathological reference are needed.\u003c/p\u003e \u003cp\u003eThe aim of the present study was therefore to compare the preoperative assessment of T stage provided by mpMRI and PSMA PET/CT in patients with prostate cancer undergoing radical prostatectomy, using final histopathology as the reference standard. Particular emphasis was placed on detection of \u0026ge;pT3 disease, including extracapsular extension (T3a) and seminal vesicle invasion (T3b).\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design and patient population\u003c/h2\u003e \u003cp\u003eThis was a prospective single-centre study including 128 consecutive patients with biopsy-proven prostate cancer who underwent PSMA PET/CT and conventional imaging (mpMRI, CT, bone scintigraphy) as part of primary staging.\u003c/p\u003e \u003cp\u003eFor the present analysis, we focused on a predefined subgroup of \u003cb\u003e51 patients\u003c/b\u003e who subsequently underwent robot-assisted radical prostatectomy (RARP) with available detailed histopathological assessment. In this subgroup, preoperative T stage determined by mpMRI and PSMA PET/CT was directly compared with the final pathological T stage. A flowchart of patient inclusion and exclusion is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eInclusion criteria for the overall cohort comprised histologically confirmed adenocarcinoma of the prostate, availability of pre-treatment mpMRI and PSMA PET/CT, and absence of prior definitive therapy, including surgery, radiotherapy or androgen deprivation therapy. For the histopathology-referenced subgroup, additional eligibility criteria included performance of radical prostatectomy after imaging and availability of a complete pathology report with pT stage assigned according to the TNM classification.\u003c/p\u003e \u003cp\u003eBasic clinical characteristics of the whole cohort (n\u0026thinsp;=\u0026thinsp;128) have been described in detail in the original study; the mean age was 67.2 years, median PSA 12 ng/mL, and the majority of patients had intermediate- or high-risk disease. These characteristics are summarised in Table\u0026nbsp;1\u003c/p\u003e \u003cp\u003e The study was approved by the local ethics committee, and all patients provided written informed consent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Imaging protocols\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Multiparametric MRI\u003c/h2\u003e \u003cp\u003eAll patients underwent mpMRI of the prostate prior to definitive treatment. Examinations were performed using a high-field MRI scanner with a pelvic phased-array coil. The standard protocol included:\u003c/p\u003e \u003cp\u003eThe standard imaging protocol consisted of high-resolution T2-weighted sequences acquired in axial, sagittal and coronal planes, diffusion-weighted imaging with generation of apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced imaging following intravenous administration of gadolinium-based contrast agent.\u003c/p\u003e \u003cp\u003eImages were interpreted by experienced radiologists according to current recommendations, with assessment of tumour location, presence of extracapsular extension (EPE) and seminal vesicle invasion (SVI). T stage was assigned following the TNM classification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 PSMA PET/CT\u003c/h2\u003e \u003cp\u003ePSMA PET/CT was performed using a dedicated PET/CT system after intravenous injection of a PSMA-targeted radiotracer (most commonly 68Ga-PSMA-11). Whole-body acquisition from the skull base to mid-thigh was obtained 60\u0026ndash;90 minutes after injection. A low-dose CT scan was used for attenuation correction and anatomical correlation.\u003c/p\u003e \u003cp\u003eImages were interpreted by nuclear medicine physicians aware of clinical data and MRI findings. The primary intraprostatic lesion, potential extracapsular extension and seminal vesicle invasion were evaluated visually on PET and fusion PET/CT images. T stage was assigned according to TNM, using a combination of uptake extent and anatomical information from CT.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Histopathological assessment\u003c/h2\u003e \u003cp\u003eAll 51 patients in the analysed subgroup underwent robot-assisted radical prostatectomy. The prostate gland, seminal vesicles and, when available, lymph nodes were examined by dedicated genitourinary pathologists. T stage was assigned according to the TNM system:\u003c/p\u003e \u003cp\u003ePathological T stage was assigned according to the TNM classification. Organ-confined disease was defined as pT2 (T2a\u0026ndash;T2c), extraprostatic extension without seminal vesicle invasion as pT3a, and seminal vesicle invasion as pT3b. For the purpose of the present analysis, locally advanced disease was defined as \u0026ge;pT3, encompassing both pT3a and pT3b.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Definition of concordance, over- and understaging\u003c/h2\u003e \u003cp\u003eFor each modality (mpMRI, PSMA PET/CT), T stage as reported in the clinical imaging report was compared with the final pT stage. Concordance was defined as identical T category between imaging and histopathology. Overstaging (upstaging) was defined as assignment of a higher T category on imaging than on histopathology; understaging (downstaging) as assignment of a lower T category.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eThe primary endpoint was the concordance rate of mpMRI and PSMA PET/CT with histopathological T stage in the 51-patient prostatectomy subgroup. Secondary endpoints included the rates of over- and understaging for each modality, diagnostic performance parameters for detection of \u0026ge;pT3 disease (including sensitivity, specificity, true positive, false negative, true negative and false positive values), and separate analyses of detection rates for pT3a (EPE) and pT3b (SVI).\u003c/p\u003e \u003cp\u003eContinuous variables are presented as means or medians with appropriate measures of dispersion; categorical variables as counts and percentages. Differences in T-stage distributions between modalities were assessed using the chi-squared test. Diagnostic performance measures (sensitivity, specificity) were calculated in relation to histopathology. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Distribution of histopathological T stage\u003c/h2\u003e \u003cp\u003eAmong the 51 patients who underwent radical prostatectomy, histopathological examination demonstrated organ-confined disease (pT1c\u0026ndash;pT2c) in 26 patients (51%), extraprostatic extension (pT3a) in 20 patients (39%), and seminal vesicle invasion (pT3b) in 5 patients (10%). Overall, locally advanced disease (\u0026ge;\u0026thinsp;pT3) was confirmed in 25 of 51 patients (49%).\u003c/p\u003e \u003cp\u003eWithin the locally advanced subgroup, extraprostatic extension (pT3a) accounted for the majority of cases (20/25; 80%), whereas seminal vesicle invasion (pT3b) was less frequent (5/25; 20%). The distribution of pathological T stages therefore demonstrated a relatively balanced proportion between organ-confined and locally advanced disease in the operated cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Concordance of mpMRI and PSMA PET/CT with histopathology\u003c/h2\u003e \u003cp\u003eThis analysis compared T-stage classification on mpMRI and PSMA PET/CT with final histopathological results in 51 patients who underwent radical prostatectomy. The distribution of T categories across modalities is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eMpMRI correctly classified the T stage in 17 of 51 patients (33%), whereas PSMA PET/CT was concordant with histopathology in 13 patients (26%). In 7 patients (14%), both imaging modalities simultaneously matched the pathological T stage. In 28 patients (55%), neither modality achieved exact concordance.\u003c/p\u003e \u003cp\u003eWithin the discordant subgroup, imaging findings differed from histopathology by only one T category in 18 cases (64%). MpMRI was closer to the pathological stage in 4 cases (14%), whereas PSMA PET/CT was closer in 6 cases (21%). Overall, at least one imaging modality correctly identified the pathological T stage in 23 of 51 patients (45%).\u003c/p\u003e \u003cp\u003eCategory-level comparison demonstrated discrepancies particularly within the T2b group. MpMRI classified 18 patients as T2b and PSMA PET/CT classified 28 patients as T2b, whereas histopathology confirmed 4 cases in this category.In the T3a category, mpMRI identified 14 cases and PSMA PET/CT identified 5 cases, while histopathology demonstrated 20 cases.\u003c/p\u003e \u003cp\u003eLower concordance was also observed in T1c and T2a categories, which were infrequent in histopathology but more frequently assigned by imaging modalities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Over- and understaging relative to histopathology\u003c/h2\u003e \u003cp\u003eIn this analysis, imaging-based T-stage classification on mpMRI and PSMA PET/CT was compared with final histopathological results in 51 patients who underwent radical prostatectomy. Exact concordance with histopathology was observed in 17 patients (33%) for mpMRI and in 13 patients (26%) for PSMA PET/CT. In seven cases (14%), both imaging modalities were concordant with the pathological T stage.\u003c/p\u003e \u003cp\u003eIn 28 patients (55%), neither modality showed exact agreement with histopathology. Within this subgroup, imaging results differed from the pathological stage by one T category in 18 cases (64%). MpMRI was closer to the pathological stage in 4 cases (14%), whereas PSMA PET/CT was closer in 6 cases (21%). Overall, at least one imaging modality correctly classified the pathological T stage in 23 patients (45%).\u003c/p\u003e \u003cp\u003eThe distribution of overstaging and understaging is presented in Table\u0026nbsp;3. For mpMRI, overstaging occurred in 5 of 51 patients (10%), while understaging was observed in 29 patients (57%). For PSMA PET/CT, overstaging occurred in 4 patients (8%) and understaging in 34 patients (67%). Understaging was more frequent than overstaging for both imaging modalities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Sensitivity and specificity relative to histopathology\u003c/h2\u003e \u003cp\u003eFor the purpose of analysing clinically relevant locally advanced disease, pT3a and pT3b cases were combined and analysed as \u0026ldquo;\u0026ge;pT3\u0026rdquo;. In the subgroup of 51 patients who underwent radical prostatectomy, histopathology confirmed \u0026ge;pT3 disease in 25 patients, while 26 patients had organ-confined disease (\u0026le;\u0026thinsp;pT2).\u003c/p\u003e \u003cp\u003eBased on imaging results, true and false classifications relative to histopathology were determined. For mpMRI, 17 true positives (TP), 8 false negatives (FN), 23 true negatives (TN) and 3 false positives (FP) were recorded. For PSMA PET/CT, 13 TP, 12 FN, 24 TN and 2 FP were observed. These data are summarised in Table\u0026nbsp;4.\u003c/p\u003e \u003cp\u003eSensitivity and specificity were calculated for both modalities (Table\u0026nbsp;5, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). For mpMRI, sensitivity was 68% and specificity was 88.5%. For PSMA PET/CT, sensitivity was 52% and specificity was 92.3%.\u003c/p\u003e \u003cp\u003eIn addition to sensitivity and specificity, positive and negative predictive values were calculated. For mpMRI, the positive predictive value (PPV) was 85% and the negative predictive value (NPV) was 74.2%. For PSMA PET/CT, PPV was 86.7% and NPV was 66.7%. Ninety-five percent confidence intervals (CI) for sensitivity were 47\u0026ndash;85% for mpMRI and 31\u0026ndash;72% for PSMA PET/CT, reflecting the limited sample size of the prostatectomy subgroup. Comparative analysis using the McNemar test did not demonstrate a statistically significant difference between the two modalities in detecting \u0026ge;pT3 disease (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Detection of pT3a (extraprostatic extension) and pT3b (seminal vesicle invasion)\u003c/h2\u003e \u003cp\u003eTo assess the performance of both imaging modalities in specific components of locally advanced disease, pT3a (extracapsular extension, EPE) and pT3b (seminal vesicle invasion, SVI) were analysed separately. Histopathology identified 20 cases of pT3a and 5 cases of pT3b in the prostatectomy cohort (Table\u0026nbsp;6).\u003c/p\u003e \u003cp\u003eFor pT3a, mpMRI identified 14 of 20 cases, corresponding to a sensitivity of 70%, while PSMA PET/CT identified 5 of 20 cases (sensitivity 25%).\u003c/p\u003e \u003cp\u003eFor pT3b, mpMRI identified 3 of 5 cases (sensitivity 60%), whereas PSMA PET/CT identified 4 of 5 cases (sensitivity 80%).\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e In this prospective single-centre study, we performed a direct comparison of mpMRI and PSMA PET/CT for preoperative local staging of prostate cancer, using radical prostatectomy histopathology as the reference standard. Several clinically relevant observations emerge from our analysis.\u003c/p\u003e \u003cp\u003eMpMRI achieved higher overall concordance with histopathological T stage than PSMA PET/CT (33% vs. 26%). Both imaging modalities more frequently underestimated rather than overestimated local tumour extent, with understaging observed in 57% of cases for mpMRI and 67% for PSMA PET/CT. In the assessment of clinically significant locally advanced disease (\u0026ge;\u0026thinsp;pT3), mpMRI demonstrated higher sensitivity (68% vs. 52%), whereas PSMA PET/CT showed slightly higher specificity (92.3% vs. 88.5%). When analysed separately, mpMRI was more sensitive in detecting extraprostatic extension (pT3a), while PSMA PET/CT demonstrated comparable performance in identifying seminal vesicle invasion (pT3b).\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that mpMRI remains more reliable for detailed evaluation of capsular integrity and early extracapsular spread, whereas PSMA PET/CT may provide complementary information, particularly in cases of more advanced local disease.\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Comparison with previous studies\u003c/h2\u003e \u003cp\u003eThe superiority of mpMRI over PSMA PET/CT in accurately determining T stage in our cohort aligns with several prior studies evaluating local staging performance. Many reports suggest that mpMRI \u0026mdash; owing to its high anatomical resolution and established radiologic criteria for EPE and SVI \u0026mdash; remains the most reliable modality for detailed assessment of the prostate capsule and periprostatic tissues (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA recent retrospective study evaluated the diagnostic performance of mpMRI and 68Ga-PSMA PET/CT in 49 patients who underwent both modalities prior to radical prostatectomy (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Using a 12-sector prostate map interpreted by uroradiologists, nuclear medicine physicians and pathologists, the authors compared intraprostatic tumour localisation and locoregional staging against whole-mount histopathology. Of 362 tumour-positive sectors, mpMRI identified 174 and PSMA PET/CT identified 175, with both modalities showing comparable accuracy for index-lesion localisation (AUC 0.69 vs. 0.66; p\u0026thinsp;=\u0026thinsp;0.82), and similar sensitivity and specificity profiles. MpMRI demonstrated significantly greater accuracy for detecting extracapsular extension (AUC 0.80 vs. 0.57; p\u0026thinsp;=\u0026thinsp;0.027), while PSMA PET/CT and mpMRI performed similarly in identifying seminal vesicle invasion, bladder neck invasion and lymph node involvement. The authors concluded that mpMRI remains the preferred modality for assessing extracapsular disease, particularly when planning nerve-sparing surgery in high-risk patients, whereas both mpMRI and PSMA PET/CT provide comparable accuracy for intraprostatic tumour localisation, and PSMA PET/CT performs reliably for nodal staging.\u003c/p\u003e \u003cp\u003eAnother study involving 70 patients who underwent mpMRI, 68Ga-PSMA PET/CT and subsequent radical prostatectomy directly compared the diagnostic performance of each modality, as well as their combined use (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe authors found no significant differences among mpMRI, PSMA PET/CT and the combined protocol in their ability to detect either index lesions or clinically significant prostate cancer, nor in their capacity to localize tumours within the superior, inferior, anterior, posterior, left or right halves of the gland. When postoperative pathology was used as the reference standard, mpMRI alone and mpMRI combined with PSMA PET/CT demonstrated acceptable accuracy for local T-stage assessment, whereas PSMA PET/CT consistently underestimated local tumour stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). For lymph node staging, all three imaging strategies showed comparable performance, with no significant differences relative to pathological nodal status. The authors concluded that PSMA PET/CT lacks reliability for local tumour staging, and that combining PSMA PET/CT with mpMRI does not offer a diagnostic advantage over mpMRI alone for lesion detection, localization or local staging.\u003c/p\u003e \u003cp\u003eSimilar findings were reported by Sonni et al., who compared the diagnostic performance of mpMRI and 68Ga-PSMA PET/CT for T-stage assessment in 74 patients with intermediate- or high-risk prostate cancer (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In this study, mpMRI demonstrated significantly higher accuracy in detecting extracapsular extension, with an AUC of 0.79 compared with 0.59 for PSMA PET/CT (p\u0026thinsp;=\u0026thinsp;0.002). A similar advantage was observed for seminal vesicle invasion, where mpMRI achieved an AUC of 0.84 versus 0.63 for PSMA PET/CT (p\u0026thinsp;=\u0026thinsp;0.001). These results clearly indicate the superiority of mpMRI over PSMA PET/CT in evaluating local tumour extent, particularly in the assessment of EPE and SVI.\u003c/p\u003e \u003cp\u003eFurther evidence supporting the advantage of mpMRI in local tumour assessment comes from a study evaluating intraprostatic lesion detection in patients undergoing HDR brachytherapy planning (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In a cohort of 27 patients who received both mpMRI and 68Ga-PSMA PET/CT, tumour localization was assessed across 24 predefined prostate segments using histopathology from targeted biopsy as the reference standard. In segment-based ROC analysis (447 segments from 19 patients), mpMRI achieved significantly higher diagnostic accuracy than PSMA PET/CT, with AUC values of 0.770 and 0.781 for two MRI readers, compared with 0.684 and 0.608 for PET/CT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Intermodality comparison similarly demonstrated superiority of mpMRI (AUC 0.815 vs. 0.690; p\u0026thinsp;=\u0026thinsp;0.006). A complementary patient-based congruence analysis confirmed higher concordance of mpMRI with biopsy results (83% vs. 76%; p\u0026thinsp;=\u0026thinsp;0.034), a difference that remained significant even after allowing near-adjacent agreement (96.5% vs. 92.7%; p\u0026thinsp;=\u0026thinsp;0.024). Overall, this study indicates that in patients with low- and intermediate-risk prostate cancer, mpMRI provides more accurate intraprostatic lesion detection than PSMA PET/CT, although larger prospective studies are needed to validate these findings.\u003c/p\u003e \u003cp\u003eOn the other hand, several authors have found encouraging performance of PSMA PET/CT, particularly in detecting dominant intraprostatic lesions and advanced disease, sometimes reporting higher sensitivity at the patient level.\u003c/p\u003e \u003cp\u003eA study by Berger et al. compared PSMA PET/CT and MRI with radical prostatectomy histopathology and demonstrated that PSMA PET/CT correctly identified all histologically confirmed tumour foci (100%), whereas MRI detected 94% of these lesions (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Moreover, PSMA PET/CT showed higher sensitivity for localisation of primary intraprostatic lesions, which may be clinically relevant, particularly in patients with more advanced disease.\u003c/p\u003e \u003cp\u003eSimilarly, a meta-analysis by Zhao et al. (2022) reported that PSMA PET/CT provides significantly higher sensitivity (0.93 vs. 0.87; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and higher AUC values (0.91 vs. 0.84) on a per-patient basis, while mpMRI offers superior specificity for localisation of individual lesions (0.88 vs. 0.71; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).This pattern suggests that PSMA PET/CT excels in overall disease detection, whereas mpMRI maintains advantages in detailed anatomical discrimination at the lesion level.\u003c/p\u003e \u003cp\u003eIn a study by Yi Yi Li et al. involving 115 patients, PSMA PET/CT demonstrated higher diagnostic specificity than MRI, particularly among individuals with PSA levels between 4 and 20 ng/mL (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Furthermore, SUVmax values showed a significant correlation with tumour aggressiveness (Gleason score), highlighting the potential role of PSMA PET/CT as a prognostic imaging biomarker.\u003c/p\u003e \u003cp\u003eOur findings align with this heterogeneous body of evidence. In our cohort, PSMA PET/CT frequently underestimated the true extent of local tumour spread, particularly in cases of subtle or early extracapsular extension. This pattern is biologically plausible: PSMA PET/CT depicts radiotracer uptake and tumour metabolism rather than the precise anatomical integrity of the prostatic capsule. Minimal capsular irregularities or microscopic extension beyond the gland may therefore remain below the detection threshold. In contrast, mpMRI provides high-resolution morphological detail and well-established indirect markers of early EPE \u0026mdash; such as capsular bulging, neurovascular bundle asymmetry or obliteration of the rectoprostatic angle \u0026mdash; which likely explains its superior sensitivity for detecting pT3a disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Clinical implications of under- and overstaging\u003c/h2\u003e \u003cp\u003eBoth understaging and overstaging may have meaningful clinical consequences in the management of prostate cancer. Underestimation of local tumour extent risks inappropriate selection of nerve-sparing radical prostatectomy in patients with true \u0026ge;pT3 disease, potentially leading to positive surgical margins or incomplete resection. Similarly, it may result in insufficient radiotherapy coverage. Conversely, overstaging may lead to unnecessarily aggressive surgical dissection or exclude patients who could otherwise be candidates for active surveillance or organ-preserving approaches.\u003c/p\u003e \u003cp\u003eA recent study assessing the concordance between mpMRI-based clinical staging (rT) and final pathological staging (pT) in patients with high-risk prostate cancer provides additional insight into the clinical consequences of staging inaccuracies (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In this cohort, mpMRI demonstrated a concordance rate of 66.4% and detected extraprostatic extension (\u0026ge;\u0026thinsp;pT3) with a sensitivity of 65.1% and an overall accuracy of 67.5%. Importantly, the authors emphasised that radiologic suspicion of \u0026ge;rT3 should not automatically preclude nerve-sparing prostatectomy. Among patients with \u0026ge;rT3 disease, 84.5% still underwent primary nerve-sparing surgery supported by the intraoperative frozen section technique (IFST), which allowed at least unilateral nerve preservation in 94.7% of cases, with a very low IFST-related positive surgical margin rate of 1.8%. These findings highlight two key points: first, mpMRI retains limitations in correctly identifying extraprostatic disease, and second, overstaging on mpMRI does not necessarily mandate abandoning nerve-sparing strategies when intraoperative verification is available. This reinforces the notion that both under- and overstaging have practical implications and that a tailored intraoperative assessment may help mitigate the risks associated with imaging inaccuracies.\u003c/p\u003e \u003cp\u003eAdditional evidence regarding the clinical implications of staging inaccuracy comes from the study by Druskin et al., which evaluated the impact of preoperative prostate MRI on nerve-sparing decisions and positive surgical margin rates in men undergoing radical prostatectomy (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In a matched comparison of 176 MRI-staged patients versus non-imaged controls, the rates of nonfocal extracapsular extension on final pathology were similar between groups, and MRI did not significantly reduce the overall rate of positive surgical margins (13.7% vs. 19.3%; p\u0026thinsp;=\u0026thinsp;0.14). Among patients with MRI findings suspicious for nonfocal extracapsular extension, the positive margin rate was higher (20.4% vs. 11.3%), and these patients underwent nerve sparing significantly less frequently, although these differences did not reach statistical significance. The authors noted that MRI findings suggesting locally advanced disease often led surgeons to adopt a more conservative intraoperative strategy, yet this did not consistently translate into improved margin status. The study underscores that while MRI can influence surgical planning\u0026mdash;particularly the decision to limit nerve preservation\u0026mdash;it may not reliably prevent positive margins, especially in patients with subtle or nonfocal extracapsular extension. These findings highlight the complex relationship between imaging-based staging, intraoperative strategy, and pathological outcomes, and illustrate how both over- and understaging may directly affect functional and oncological results.\u003c/p\u003e \u003cp\u003eIn our cohort, understaging was more common than overstaging for both imaging modalities, with PSMA PET/CT demonstrating a particularly strong tendency to underestimate the true extent of local disease (67% of cases). This pattern further reinforces concerns raised in previous studies and highlights that PSMA PET/CT alone may be insufficient for surgical planning when the primary focus is accurate evaluation of capsular involvement. MpMRI, although not free from limitations, provided a more favourable balance between sensitivity and specificity and therefore offered more dependable preoperative guidance for identifying patients at risk of \u0026ge;pT3 disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Detection of pT3a vs. pT3b: complementary strengths\u003c/h2\u003e \u003cp\u003eThe distinction between pT3a and pT3b is clinically relevant, as these entities differ in biological behaviour and surgical implications. In our subgroup analysis, mpMRI demonstrated higher sensitivity for the detection of extraprostatic extension, identifying 14 of 20 histopathologically confirmed pT3a cases (70%), compared with 5 of 20 cases detected by PSMA PET/CT (25%). This finding is consistent with the established role of mpMRI in assessing capsular integrity and periprostatic anatomy.\u003c/p\u003e \u003cp\u003eIn contrast, for seminal vesicle invasion (pT3b), PSMA PET/CT detected 4 of 5 cases (80%), whereas mpMRI identified 3 of 5 cases (60%). Although the number of pT3b cases in our cohort was limited, these results suggest that PSMA PET/CT may perform comparably to mpMRI in the assessment of seminal vesicle involvement.\u003c/p\u003e \u003cp\u003eTaken together, the differential performance observed for pT3a and pT3b indicates that the diagnostic strengths of mpMRI and PSMA PET/CT are not identical. MpMRI appears to be more sensitive for early extracapsular extension, while PSMA PET/CT may provide complementary information in cases of suspected seminal vesicle invasion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e4.4 Strengths and limitations\u003c/h2\u003e \u003cp\u003eThe present study has several strengths. It was designed as a prospective single-centre investigation and utilised radical prostatectomy histopathology as the reference standard for T-stage assessment. The analysed cohort consisted predominantly of patients with intermediate- and high-risk disease, reflecting a clinically relevant population in whom accurate local staging is particularly important. Furthermore, both imaging modalities were performed preoperatively within routine clinical workflows, which enhances the real-world applicability of the results.\u003c/p\u003e \u003cp\u003eCertain limitations should also be considered. The prostatectomy subgroup was relatively small (n\u0026thinsp;=\u0026thinsp;51), which limits the statistical power of subgroup analyses, especially for pT3b. The single-centre design may reflect institution-specific expertise in mpMRI and PSMA PET/CT interpretation and may therefore restrict generalisability. In addition, T-stage assessment was performed on a whole-gland basis, without lesion-level or sector-based correlation with whole-mount histopathology. Interobserver variability was not formally evaluated, as imaging reports were based on routine clinical interpretation.\u003c/p\u003e \u003cp\u003eDespite these limitations, the overall consistency of our findings with previously published data supports the robustness of the observed patterns.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e4.5 Future directions\u003c/h2\u003e \u003cp\u003eFuture research should include larger multicentre cohorts with standardised imaging protocols, blinded interpretation and systematic whole-mount histopathological correlation. Such study designs would allow more precise evaluation of the complementary roles of mpMRI and PSMA PET/CT in local T-stage assessment.\u003c/p\u003e \u003cp\u003eHybrid imaging techniques, particularly PSMA PET/MRI, represent a potential avenue for integrating molecular and anatomical information within a single examination. In addition, quantitative imaging parameters\u0026mdash;including PET-derived SUV metrics and MRI-based morphological or radiomic features\u0026mdash;may support the development of predictive models for extracapsular extension and seminal vesicle invasion.\u003c/p\u003e \u003cp\u003eRecent work has explored practical strategies for combining mpMRI and PSMA PET/CT findings to improve detection of extraprostatic extension (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In a cohort of 67 patients undergoing radical prostatectomy, integration of MRI-based capsular contact length with PET-derived SUVmax improved the balance between sensitivity and specificity for EPE detection. These findings suggest that structured multimodal assessment may enhance preoperative risk stratification beyond either modality alone.\u003c/p\u003e \u003cp\u003eFinally, the application of artificial intelligence to combined mpMRI and PSMA PET/CT datasets may further refine diagnostic accuracy, reduce interobserver variability and contribute to more individualised treatment planning.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn this prospective single-centre study, mpMRI and PSMA PET/CT were directly compared for preoperative local T-stage assessment in patients undergoing radical prostatectomy, using histopathology as the reference standard.\u003c/p\u003e \u003cp\u003eMpMRI demonstrated higher overall concordance with pathological T stage and greater sensitivity for detecting \u0026ge;pT3 disease, particularly extraprostatic extension (pT3a). PSMA PET/CT showed slightly higher specificity but a pronounced tendency toward understaging of local tumour extent. In contrast, performance for seminal vesicle invasion (pT3b) was comparable between modalities.\u003c/p\u003e \u003cp\u003eThese findings support the continued use of mpMRI as the primary imaging modality for local staging, particularly when surgical planning depends on accurate assessment of capsular involvement. PSMA PET/CT should not replace mpMRI in local T-stage evaluation but may provide complementary information, especially in patients with suspected seminal vesicle invasion or when integrated local and systemic staging is required.\u003c/p\u003e \u003cp\u003eFurther validation in larger multicentre cohorts with standardised imaging protocols and whole-mount pathological correlation is warranted to define optimal strategies for integrating mpMRI and PSMA-based imaging in preoperative staging.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstate\u0026ndash;specific membrane antigen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePET/CT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePositron emission tomography/computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003empMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultiparametric magnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSUVmax\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMaximum standardized uptake value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstate\u0026ndash;specific antigen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISUP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Society of Urological Pathology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor, Node, Metastasis classification\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEPE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExtraprostatic extension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRARP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRobot\u0026ndash;assisted radical prostatectomy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethics Committee at the Regional Medical Chamber in Zielona Góra (approval no. 06/142/2021). All patients provided informed consent.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eOP: study design, data collection, analysis, manuscript preparation\u003c/p\u003e\n\u003cp\u003ePP: study supervision, data interpretation, manuscript revision\u003c/p\u003e\n\u003cp\u003ePZ: data acquisition and interpretation of imaging studies\u003c/p\u003e\n\u003cp\u003ePS: data collection and patient management\u003c/p\u003e\n\u003cp\u003eMG: data collection and clinical data analysis\u003c/p\u003e\n\u003cp\u003eKBJ: data acquisition and data organization\u003c/p\u003e\n\u003cp\u003eTD: study supervision and critical revision of the manuscript\u003c/p\u003e\n\u003cp\u003eKK: data analysis and methodological support\u003c/p\u003e\n\u003cp\u003eJA: study supervision, study design, and critical revision of the manuscript\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study, reviewed the manuscript, and approved the final version.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all patients who participated in this study.\u003c/p\u003e\n\u003cp\u003eAuthors’ information\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarsouk A, Padala SA, Vakiti A, Mohammed A, Saginala K, Thandra KC et al. Epidemiology, Staging and Management of Prostate Cancer. Vol. 8, Medical sciences (Basel, Switzerland). 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDell\u0026rsquo;Atti L. Biparametric MRI for Local Staging of Prostate Cancer: Current Status and Future Applications. 44, Anticancer Res. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandrasekar T, Denisenko A, Mico V, McPartland C, Shah Y, Mark JR et al. Multiparametric MRI is not sufficient for prostate cancer staging: A single institutional experience validated by a multi-institutional regional collaborative. Urologic Oncology: Seminars Original Investigations. 2023;41(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLenis AT, Pooli A, Lec PM, Sadun TY, Johnson DC, Lebacle C et al. Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-na\u0026iuml;ve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study. Eur Urol Oncol. 2022;5(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKleiburg F, Heijmen L, Gelderblom H, Kielbasa SM, Bov\u0026eacute;e JV, De Geus-Oei LF. Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas. 96, Br J Radiol. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Man K, Van Laeken N, Schelfhout V, Fendler WP, Lambert B, Kersemans K et al. 18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial. Eur Urol. 2022;82(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDondi F, Albano D, Bertagna F, Treglia G. Bone Scintigraphy versus PSMA-Targeted PET/CT or PET/MRI in Prostate Cancer: Lessons Learned from Recent Systematic Reviews and Meta-Analyses. Vol. 14, Cancers. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChow KM, So WZ, Lee HJ, Lee A, Yap DWT, Takwoingi Y et al. Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis. Vol. 84, European Urology. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Klot CAJ, Merseburger AS, B\u0026ouml;ker A, Schmuck S, Ross TL, Bengel FM et al. 68Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent, Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer. Nucl Med Mol Imaging. 2017;51(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin Y, Johnson LA, Fennessy FM, Turkbey B. Prostate Cancer Local Staging with Magnetic Resonance Imaging. Volume 62. Radiologic Clinics of North America; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValentin B, Schimm\u0026ouml;ller L, Ullrich T, Klingebiel M, Demetrescu D, Sawicki LM et al. Magnetic resonance imaging improves the prediction of tumor staging in localized prostate cancer. Abdom Radiol. 2021;46(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTriquell M, Regis L, Winkler M, Vald\u0026eacute;s N, Cuadras M, Celma A et al. Multiparametric MRI for Staging of Prostate Cancer: A Multicentric Analysis of Predictive Factors to Improve Identification of Extracapsular Extension before Radical Prostatectomy. Cancers (Basel). 2022;14(16).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUcar T, Gunduz N, Demirci E, Culpan M, Gunel H, Kir G et al. Comparison of 68Ga-PSMA PET/CT and mp-MRI in regard to local staging for prostate cancer with histopathological results: A retrospective study. Prostate. 2022;82(15).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMai Z, Zhu M, Feng T, Zhou Z, Zhou Y, Wang D et al. Comparisons of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in diagnosing prostate cancer based on tumor detection, localization and staging. World J Urol. 2024;42(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSonni I, Felker ER, Lenis AT, Sisk AE, Bahri S, Allen-Auerbach M et al. Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI with histopathology gold-standard in the detection, intra-prostatic localization and local extension of primary prostate cancer: results from a prospective single-center imaging trial. J Nucl Med. 2022;63(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoritz J, Argow S, Hupfeld SA, Schenke S, Neumann R, Damm J, Vogt, et al. Comparison of mpMRI and 68Ga-PSMA-PET/CT in the Assessment of the Primary Tumors in Predominant Low-/Intermediate-Risk Prostate Cancer. Diagnostics (Basel). 2025;15(11):1358.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerger I, Annabattula C, Lewis J, Shetty DV, Kam J, MacLean F et al. 68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: Correlation with final histopathology. Prostate Cancer Prostatic Dis. 2018;21(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao G, Ji B. Head-To-Head Comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP Bone Scintigraphy for the Detection of Bone Metastases in Patients with Prostate Cancer: A Meta-Analysis. Volume 219. American Journal of Roentgenology; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Han D, Wu P, Ren J, Ma S, Zhang J et al. Comparison of 68Ga-PSMA-617 PET/CT with mpMRI for the detection of PCa in patients with a PSA level of 4\u0026ndash;20 ng/ml before the initial biopsy. Sci Rep. 2020;10(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHumke C, Hoeh B, Preisser F, Wenzel M, Welte MN, Theissen L et al. Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer. Curr Oncol. 2022;29(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDruskin SC, Liu JJ, Young A, Feng Z, Dianat SS, Ludwig WW et al. Prostate mri prior to radical prostatectomy: Effects on nerve sparing and pathological margin status. Res Rep Urol. 2017;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSungmin Woo D, Freedman AS, Becker D, Leithner C, Charbel, Marius E, Mayerhoefer, et al. Evaluating extraprostatic extension of prostate cancer: pragmatic integration of MRI and PSMA-PET/CT. Abdom Radiol (NY). 2025;50(11):5274\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Baseline characteristics of the study population\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eClinical data\u003c/th\u003e\n \u003cth\u003eValue\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003eMean age (years)\u003c/td\u003e\n \u003ctd\u003e67,2\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eMedian age (years)\u003c/td\u003e\n \u003ctd\u003e68\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eAge range (years)\u003c/td\u003e\n \u003ctd\u003e45-82\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eMean level PSA (ng/ml)\u003c/td\u003e\n \u003ctd\u003e15,27\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eMedian PSA (ng/ml)\u003c/td\u003e\n \u003ctd\u003e12\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ePSA range (ng/ml)\u003c/td\u003e\n \u003ctd\u003e1,85-55\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eRisk group low-risk\u003c/td\u003e\n \u003ctd\u003e17\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eRisk group intermediate-risk\u003c/td\u003e\n \u003ctd\u003e42\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eRisk group high-risk\u003c/td\u003e\n \u003ctd\u003e69\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eISUP I\u003c/td\u003e\n \u003ctd\u003e32\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eISUP II\u003c/td\u003e\n \u003ctd\u003e31\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eISUP III\u003c/td\u003e\n \u003ctd\u003e22\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eISUP IV\u003c/td\u003e\n \u003ctd\u003e24\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eISUP V\u003c/td\u003e\n \u003ctd\u003e19\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eTable 2. Concordance of mpMRI and PSMA PET/CT with histopathology in T staging\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eHistopathological result\u003c/th\u003e\n \u003cth\u003eMRI\u003c/th\u003e\n \u003cth\u003ePSMA PET/CT\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003eMatches histopathology\u003c/td\u003e\n \u003ctd\u003e17\u003c/td\u003e\n \u003ctd\u003e13\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eBoth match\u003c/td\u003e\n \u003ctd\u003e7\u003c/td\u003e\n \u003ctd\u003e7\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eRemaining cases\u003c/td\u003e\n \u003ctd\u003e28\u003c/td\u003e\n \u003ctd\u003e28\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eComparable concordance\u003c/td\u003e\n \u003ctd\u003e18\u003c/td\u003e\n \u003ctd\u003e18\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003eMRI greater concordance\u003c/td\u003e\n \u003ctd\u003e4\u003c/td\u003e\n \u003ctd\u003e-\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ePSMA PET/CT greater concordance\u003c/td\u003e\n \u003ctd\u003e-\u003c/td\u003e\n \u003ctd\u003e6\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eTable 3. Distribution of overstaging and understaging in mpMRI and PSMA PET/CT\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eImaging modality\u003c/th\u003e\n \u003cth\u003eUpstaging\u003c/th\u003e\n \u003cth\u003eDownstaging\u003c/th\u003e\n \u003cth\u003eNo differences\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003eMRI\u003c/td\u003e\n \u003ctd\u003e5 cases\u003c/td\u003e\n \u003ctd\u003e29 cases\u003c/td\u003e\n \u003ctd\u003e17 cases\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ePSMA PET/CT\u003c/td\u003e\n \u003ctd\u003e4 cases\u003c/td\u003e\n \u003ctd\u003e34 cases\u003c/td\u003e\n \u003ctd\u003e13 cases\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eTable 4. True and false classifications of mpMRI and PSMA PET/CT relative to histopathology\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eImaging modality\u003c/th\u003e\n \u003cth\u003eTP\u003c/th\u003e\n \u003cth\u003eFN\u003c/th\u003e\n \u003cth\u003eTN\u003c/th\u003e\n \u003cth\u003eFP\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003eMRI\u003c/td\u003e\n \u003ctd\u003e17\u003c/td\u003e\n \u003ctd\u003e8\u003c/td\u003e\n \u003ctd\u003e23\u003c/td\u003e\n \u003ctd\u003e3\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ePSMA PET/CT\u003c/td\u003e\n \u003ctd\u003e13\u003c/td\u003e\n \u003ctd\u003e12\u003c/td\u003e\n \u003ctd\u003e24\u003c/td\u003e\n \u003ctd\u003e2\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eTable 5. Sensitivity and specificity of mpMRI and PSMA PET/CT\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eImaging modality\u003c/th\u003e\n \u003cth\u003eSensitivity (%)\u003c/th\u003e\n \u003cth\u003eSpecificity (%)\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003eMRI\u003c/td\u003e\n \u003ctd\u003e68%\u003c/td\u003e\n \u003ctd\u003e88.5%\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ePSMA PET/CT\u003c/td\u003e\n \u003ctd\u003e52%\u003c/td\u003e\n \u003ctd\u003e92.3%\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eTable 6. Detection of pT3a (EPE) and pT3b (SVI) by mpMRI and PSMA PET/CT\u003c/p\u003e\n \u003ctable\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003eCategory\u003c/th\u003e\n \u003cth\u003eHistopathology (n)\u003c/th\u003e\n \u003cth\u003eMRI (n)\u003c/th\u003e\n \u003cth\u003eSensitivity MRI (%)\u003c/th\u003e\n \u003cth\u003ePSMA PET/CT\u003c/th\u003e\n \u003cth\u003eSensitivity PSMA PET/CT (%)\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003ecT3a (EPE)\u003c/td\u003e\n \u003ctd\u003e20\u003c/td\u003e\n \u003ctd\u003e14\u003c/td\u003e\n \u003ctd\u003e70\u003c/td\u003e\n \u003ctd\u003e5\u003c/td\u003e\n \u003ctd\u003e25\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003ecT3b (SVI)\u003c/td\u003e\n \u003ctd\u003e5\u003c/td\u003e\n \u003ctd\u003e3\u003c/td\u003e\n \u003ctd\u003e60\u003c/td\u003e\n \u003ctd\u003e4\u003c/td\u003e\n \u003ctd\u003e80\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\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":"","lastPublishedDoi":"10.21203/rs.3.rs-9141498/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9141498/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eAccurate assessment of local tumour stage (T stage) is essential for selecting optimal treatment in patients with prostate cancer. Multiparametric MRI (mpMRI) is currently the reference imaging modality for local staging, while PSMA PET/CT has emerged as a highly sensitive technique for nodal and distant disease. However, its role in evaluating local tumour extent remains unclear. The aim of this prospective study was to compare the accuracy of mpMRI and PSMA PET/CT in preoperative T staging using radical prostatectomy histopathology as the reference standard.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eA total of 128 patients with biopsy-proven prostate cancer underwent both mpMRI and PSMA PET/CT before treatment. In a subgroup of 51 patients treated with radical prostatectomy, histopathology confirmed \u0026ge;pT3 disease in 25 patients (49%), including 20 cases of pT3a and 5 of pT3b. MpMRI correctly identified the pathological T stage in 17 patients (33%), whereas PSMA PET/CT was concordant in 13 patients (26%). Both modalities matched histopathology in 7 cases (14%). MpMRI overstaged disease in 10% of patients and understaged in 57%, while PSMA PET/CT overstaged in 8% and understaged in 67%. For detection of \u0026ge;pT3 disease, mpMRI demonstrated a sensitivity of 68% and specificity of 88.5%, compared with 52% and 92.3% for PSMA PET/CT, respectively. MpMRI showed higher sensitivity for detecting extraprostatic extension (70% vs 25%), whereas PSMA PET/CT demonstrated comparable or slightly higher performance for seminal vesicle invasion (80% vs 60%).\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003e MpMRI demonstrated higher sensitivity and overall concordance with histopathology in the assessment of local tumour stage, particularly for extraprostatic extension. PSMA PET/CT showed higher specificity but tended to underestimate local disease extent. These findings support mpMRI as the primary imaging modality for local staging, while PSMA PET/CT should be considered a complementary tool, particularly in the context of combined local and systemic staging.\u003c/p\u003e","manuscriptTitle":"Preoperative Local Staging of Prostate Cancer: Comparison of mpMRI and PSMA PET/CT Against Radical Prostatectomy Histopathology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-31 17:32:53","doi":"10.21203/rs.3.rs-9141498/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":"a15ccccf-d130-46f0-a56a-57a97cceb9ca","owner":[],"postedDate":"March 31st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-12T13:40:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-31 17:32:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9141498","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9141498","identity":"rs-9141498","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}