PI‐RADS in Predicting csPCa: A Comparison Between Academic and Nonacademic Centers
Introduction Prostate cancer (PCa) is the leading malignant tumor in men, with 288,300 new cases (29% of all cancers in men) and 34,700 deaths (11% of all cancer deaths) recorded in 2023 in the United States . The introduction of multiparametric prostate magnetic resonance imaging (mpMRI) in recent years has revolutionized the diagnosis of PCa. Today, mpMRI is considered the best radiological exam for localizing suspicious areas of clinically significant prostate cancer (csPCa) and the European Association of Urology (EAU) guidelines recommend performing mpMRI before conducting a biopsy in patients suspected to have csPCa . Interpreting prostate mpMRIs is complex and requires thorough and supervised training indeed, despite the availability of standardized protocols for reporting mpMRI results, there is considerable variability among radiologists with different levels of expertise . Research has shown that less experienced radiologists are more likely to produce inconclusive or incorrect mpMRI reports, resulting in higher rates of false positives . Over time, despite the recognized importance of mpMRI in PCa patients, significant multicenter disparities have been identified in the execution, interpretation, and reporting of prostate MRI examinations. This has underscored the need for greater standardization and accuracy in these procedures . This study aims to evaluate the diagnostic efficacy of mpMRI obtained from both academic and nonacademic centers in detecting csPCa using the MRI/US fusion biopsy technique. 

Materials and Methods 2.1 Patients Between July 2018 and October 2023, at our center, SS. Annunziata Hospital of Chieti, we prospectively followed 810 men who underwent prostate biopsies with the MRI/US fusion technique due to elevated prostate‐specific antigen (PSA) and/or abnormal digital rectal examination (DRE). We included all patients with a positive mpMRI documenting suspicious lesions for PCa classified with a PI‐RADS score ≥ 3. Patients could be biopsy‐naive, have had previous negative biopsies, or be on active surveillance. Patients without prebiopsy mpMRI or with mpMRI not available were excluded. Then we differentiated two groups of patients based on where they had their mpMRI performed, either at academic or nonacademic centers. An academic center is defined as a teaching hospital affiliated with a medical school, often involved in research and training future healthcare professionals. In contrast, a nonacademic center is a healthcare facility that is not affiliated with a medical school and primarily focuses on patient care without a significant emphasis on research or teaching activities . The academic centers included in this study were two, while the nonacademic centers were four. Comprehensive data, including clinical information, mpMRI findings, and pathological results, were collected for each patient. All participants provided written informed consent. Ethics approval was obtained from our institution, and patient demographic factors, disease factors, as well as peri‐ and postprocedure details were compiled and anonymized. 2.2 mpMRI, Biopsy, and Pathology Of the patients included in the study, we collected data regarding the mpMRI performed. The morphological study using the T2‐weighted sequence and the functional study using DWI and dynamic contrast‐enhanced sequences, which included the seminal vesicles and prostate gland, were conducted with 1.5T and 3T scanners. In each centers, all lesions were scored using the Prostate Imaging‐Reporting and Data System (PI‐PRADS) version 2.1 . Biopsies were conducted in a single tertiary center, in an ambulatory setting. A peri‐prostatic nerve blockade with 2% lidocaine was administered immediately before the biopsy. Each urologist independently decided whether to start with systematic or targeted sampling, ensuring comprehensive coverage of the base, mid area, and apex for both lobes in addition to the suspicious areas . All biopsies were conducted using the MRI/US fusion technique and a trans‐rectal approach by three expert urologists using the BK Medical system. A single pathologist meticulously assessed every specimen in accordance with the criteria set forth by the Standards of Reporting for MRI‐Targeted Biopsy Studies (START) . The histopathological analysis was reported using a Gleason score and the International Society of Urologic Pathology (ISUP) . Patients with benign conditions, clinically insignificant PCa, and clinically significant PCa were identified. 2.3 Statistical Analysis Descriptive statistics were calculated according to variable distribution to provide a comprehensive overview of the data. These included measures of central tendency (median) and dispersion ([first; third] quartile) for continuous variables, as well as frequencies and percentages for categorical variables. Normality distribution for quantitative variables was assessed by the Shapiro–Wilk Test. A Sankey Diagram was also used to visualize the flow distribution between variables: PSA, DRE, Center, PIRADS, and ISUP. The Sankey Diagram helps to understand the pathways and proportions of various transitions or interactions within the data. The Mann‐Whitney test was used to compare differences between types of centers for continuous variables. The chi‐squared test assessed a possible association between the type of center and categorical variables. Crude odds ratio (ORs) and corresponding 95% confidence interval (CI) were calculated using the Wald test to quantify the risk associated with the considered explicative variables for the endpoint variable (csPCa). A multivariable logistic regression model was used to identify the mutually adjusted effect among csPCa diagnoses, including an interaction term to investigate the combined effect of belonging to a specific type of Center (academic vs. nonacademic) and having a PIRADS greater than 3. By including this interaction term, we aimed to understand whether the impact of a high PIRADS score on the outcome differs depending on the type of Center. All tests were two‐sided, and a level of statistical significance was set at p < 0.05. Analyses were performed using the R software environment for statistical computing and graphics (version 4.2). 

Patients Between July 2018 and October 2023, at our center, SS. Annunziata Hospital of Chieti, we prospectively followed 810 men who underwent prostate biopsies with the MRI/US fusion technique due to elevated prostate‐specific antigen (PSA) and/or abnormal digital rectal examination (DRE). We included all patients with a positive mpMRI documenting suspicious lesions for PCa classified with a PI‐RADS score ≥ 3. Patients could be biopsy‐naive, have had previous negative biopsies, or be on active surveillance. Patients without prebiopsy mpMRI or with mpMRI not available were excluded. Then we differentiated two groups of patients based on where they had their mpMRI performed, either at academic or nonacademic centers. An academic center is defined as a teaching hospital affiliated with a medical school, often involved in research and training future healthcare professionals. In contrast, a nonacademic center is a healthcare facility that is not affiliated with a medical school and primarily focuses on patient care without a significant emphasis on research or teaching activities . The academic centers included in this study were two, while the nonacademic centers were four. Comprehensive data, including clinical information, mpMRI findings, and pathological results, were collected for each patient. All participants provided written informed consent. Ethics approval was obtained from our institution, and patient demographic factors, disease factors, as well as peri‐ and postprocedure details were compiled and anonymized. 

mpMRI, Biopsy, and Pathology Of the patients included in the study, we collected data regarding the mpMRI performed. The morphological study using the T2‐weighted sequence and the functional study using DWI and dynamic contrast‐enhanced sequences, which included the seminal vesicles and prostate gland, were conducted with 1.5T and 3T scanners. In each centers, all lesions were scored using the Prostate Imaging‐Reporting and Data System (PI‐PRADS) version 2.1 . Biopsies were conducted in a single tertiary center, in an ambulatory setting. A peri‐prostatic nerve blockade with 2% lidocaine was administered immediately before the biopsy. Each urologist independently decided whether to start with systematic or targeted sampling, ensuring comprehensive coverage of the base, mid area, and apex for both lobes in addition to the suspicious areas . All biopsies were conducted using the MRI/US fusion technique and a trans‐rectal approach by three expert urologists using the BK Medical system. A single pathologist meticulously assessed every specimen in accordance with the criteria set forth by the Standards of Reporting for MRI‐Targeted Biopsy Studies (START) . The histopathological analysis was reported using a Gleason score and the International Society of Urologic Pathology (ISUP) . Patients with benign conditions, clinically insignificant PCa, and clinically significant PCa were identified. 

Statistical Analysis Descriptive statistics were calculated according to variable distribution to provide a comprehensive overview of the data. These included measures of central tendency (median) and dispersion ([first; third] quartile) for continuous variables, as well as frequencies and percentages for categorical variables. Normality distribution for quantitative variables was assessed by the Shapiro–Wilk Test. A Sankey Diagram was also used to visualize the flow distribution between variables: PSA, DRE, Center, PIRADS, and ISUP. The Sankey Diagram helps to understand the pathways and proportions of various transitions or interactions within the data. The Mann‐Whitney test was used to compare differences between types of centers for continuous variables. The chi‐squared test assessed a possible association between the type of center and categorical variables. Crude odds ratio (ORs) and corresponding 95% confidence interval (CI) were calculated using the Wald test to quantify the risk associated with the considered explicative variables for the endpoint variable (csPCa). A multivariable logistic regression model was used to identify the mutually adjusted effect among csPCa diagnoses, including an interaction term to investigate the combined effect of belonging to a specific type of Center (academic vs. nonacademic) and having a PIRADS greater than 3. By including this interaction term, we aimed to understand whether the impact of a high PIRADS score on the outcome differs depending on the type of Center. All tests were two‐sided, and a level of statistical significance was set at p < 0.05. Analyses were performed using the R software environment for statistical computing and graphics (version 4.2). 

Results 3.1 Patient Demographics and Characteristics Between July 2018 and October 2023, 810 men who underwent prostate biopsies with the MRI/US fusion technique were prospectively followed. The cohort was divided into two groups based on the location where the mpMRI was performed: academic centers (354 patients) and nonacademic centers (456 patients). The study included two academic centers (C1 and C2) and three nonacademic centers (C3, C4, C5, and C6). Specifically, 200 mpMRIs were performed at C1, 154 at C2, 156 at C3, 104 at C4, 61 at C5, and 135 at C6. In the Academic Center, the procedures performed using 3T technology were 115 (32.49%), while in the nonacademic center, they were 150 (32.89%) ( p = 0.90). The median age of the cohort was 68 years (IQR: 62–73 years), with no significant difference between the groups (68 vs. 68 years, p = 0.757). The median PSA level was 6.63 ng/mL (IQR: 4.79–10.0 ng/mL), with no significant difference between the academic and nonacademic groups (6.50 vs. 6.78 ng/mL, p = 0.324). Additionally, the groups had no statistically significant differences in abnormal DRE findings or the use of 5‐alpha‐reductase inhibitors (5‐ARI) (Table ). The pathways and outcomes for patients in academic versus nonacademic centers are highlighted in Figure . In our cohort, the analysis revealed that increasing age had an OR: 1.08 [CI: 1.05–1.10], p < 0.001 and PSA levels (OR: 1.07 [CI: 1.04–1.09]; p < 0.001) were associated with a higher risk of csPCa. Median PSA density was significantly higher in patients with csPCa compared to those without csPCa (0.14 vs. 0.11 ng/mL/cm³, p < 0.001). A positive DRE was also associated with a higher risk of csPCa (OR: 4.22 [CI: 2.78–6.51]; p < 0.001), while a larger prostate volume was associated with a lower risk (OR: 0.98 [CI: 0.97–0.99]; p < 0.001) (Table ). 3.2 PIRADS Scores and Biopsy Samples The cohort included patients with PIRADS scores of 3, 4, and 5, accounting for 33.2%, 54.1%, and 12.7% of the total, respectively. Patients at academic centers were more likely to receive a higher number of elevated PIRADS scores compared to those at nonacademic centers (PIRADS > 3: 72.6% vs. 62.3%, p = 0.003). The total number of core samples did not differ significantly between groups ( p = 0.063), with both groups having a similar median number of core samples taken, which were 13 (12–14) and 13 (12–15), respectively. 3.3 Histopathological Findings and Detection of Clinically Significant Cancer Histopathological analysis revealed that 59.6% of patients had benign conditions, while the remaining cases were categorized as follows: ISUP grade I (5.9%), II (15.3%), III (6.9%), IV (7.7%), and V (4.6%). When examining individual groups, 62.1% of patients at Academic centers had benign findings on biopsy, compared to 57.7% at nonacademic centers ( p = 0.198). Regarding the likelihood of detecting csPCa in patients with PI‐RADS 3 at Academic Centers, OR for nonacademic centers was 1.09 [CI: 0.64–1.86, p > 0.05]. For patients with PI‐RADS > 3, the OR was 2.37 [CI: 1.44–3.91, p < 0.01] at nonacademic centers and 3.49 [CI: 2.00–6.11, p < 0.001] at academic centers (Figure ). 

Patient Demographics and Characteristics Between July 2018 and October 2023, 810 men who underwent prostate biopsies with the MRI/US fusion technique were prospectively followed. The cohort was divided into two groups based on the location where the mpMRI was performed: academic centers (354 patients) and nonacademic centers (456 patients). The study included two academic centers (C1 and C2) and three nonacademic centers (C3, C4, C5, and C6). Specifically, 200 mpMRIs were performed at C1, 154 at C2, 156 at C3, 104 at C4, 61 at C5, and 135 at C6. In the Academic Center, the procedures performed using 3T technology were 115 (32.49%), while in the nonacademic center, they were 150 (32.89%) ( p = 0.90). The median age of the cohort was 68 years (IQR: 62–73 years), with no significant difference between the groups (68 vs. 68 years, p = 0.757). The median PSA level was 6.63 ng/mL (IQR: 4.79–10.0 ng/mL), with no significant difference between the academic and nonacademic groups (6.50 vs. 6.78 ng/mL, p = 0.324). Additionally, the groups had no statistically significant differences in abnormal DRE findings or the use of 5‐alpha‐reductase inhibitors (5‐ARI) (Table ). The pathways and outcomes for patients in academic versus nonacademic centers are highlighted in Figure . In our cohort, the analysis revealed that increasing age had an OR: 1.08 [CI: 1.05–1.10], p < 0.001 and PSA levels (OR: 1.07 [CI: 1.04–1.09]; p < 0.001) were associated with a higher risk of csPCa. Median PSA density was significantly higher in patients with csPCa compared to those without csPCa (0.14 vs. 0.11 ng/mL/cm³, p < 0.001). A positive DRE was also associated with a higher risk of csPCa (OR: 4.22 [CI: 2.78–6.51]; p < 0.001), while a larger prostate volume was associated with a lower risk (OR: 0.98 [CI: 0.97–0.99]; p < 0.001) (Table ). 

PIRADS Scores and Biopsy Samples The cohort included patients with PIRADS scores of 3, 4, and 5, accounting for 33.2%, 54.1%, and 12.7% of the total, respectively. Patients at academic centers were more likely to receive a higher number of elevated PIRADS scores compared to those at nonacademic centers (PIRADS > 3: 72.6% vs. 62.3%, p = 0.003). The total number of core samples did not differ significantly between groups ( p = 0.063), with both groups having a similar median number of core samples taken, which were 13 (12–14) and 13 (12–15), respectively. 

Histopathological Findings and Detection of Clinically Significant Cancer Histopathological analysis revealed that 59.6% of patients had benign conditions, while the remaining cases were categorized as follows: ISUP grade I (5.9%), II (15.3%), III (6.9%), IV (7.7%), and V (4.6%). When examining individual groups, 62.1% of patients at Academic centers had benign findings on biopsy, compared to 57.7% at nonacademic centers ( p = 0.198). Regarding the likelihood of detecting csPCa in patients with PI‐RADS 3 at Academic Centers, OR for nonacademic centers was 1.09 [CI: 0.64–1.86, p > 0.05]. For patients with PI‐RADS > 3, the OR was 2.37 [CI: 1.44–3.91, p < 0.01] at nonacademic centers and 3.49 [CI: 2.00–6.11, p < 0.001] at academic centers (Figure ). 

Discussion The introduction of mpMRI into the diagnostic workflow for PCa has been transformative, making it an essential step before almost any prostate biopsy . This innovation has significantly altered the biopsy approach, allowing for a reduction in the number of biopsy cores taken without compromising diagnostic accuracy . It also enables the avoidance of biopsies in patients with low risk, without missing csPCa . To have an important role in clinical practice, it was necessary to standardize this procedure. In 2012, the European Society of Urogenital Radiology (ESUR) developed the PI‐RADS v1 to standardize radiological reports of these suspicious areas . The American College of Radiology and the PI‐RADS Steering Committee released PI‐RADS v2, widely accepted for its high accuracy in detecting csPCa . However, initial data showed low to moderate interobserver agreement among readers with varying levels of experience . To address the limitations of PI‐RADS v2 and improve reproducibility by clarifying certain descriptors, PI‐RADS v2.1 was published in 2019 . PI‐RADS v2 system improved over PI‐RADS v1 regarding sensitivity and reader agreement. PI‐RADS v2 has an average sensitivity of 91% for detecting index lesions, compared to 78% for v1 . Additionally, reader agreement for PI‐RADS v2 is 93% for index lesions, a significant improvement over v1, which had higher variability in image interpretation . In our study, we observed general characteristics consistent with the literature: increasing age and PSA levels are associated with a higher risk of clinically significant prostate cancer (csPCa). Additionally, a significantly larger portion of patients with csPCa had a positive DRE compared to those without csPCa (25.1% vs. 7.32%, p < 0.001). However, the aspect we aimed to emphasize the most was the significant intra‐center differences in PI‐RADS scoring, with patients from academic centers tend to receive a higher number of elevated PIRADS scores compared to those from nonacademic centers. Median PSA density was significantly higher in patients with csPCa compared to those without csPCa (0.14 vs. 0.11 ng/mL/cm³, p < 0.001). This finding is consistent with prior studies, such as the work of Benson et al. which demonstrated that PSA density provides a better distinction between benign prostatic hyperplasia (BPH) and PCa compared to PSA alone. The study emphasized that PSA density facilitates the correlation of serum PSA and prostate volume, improving diagnostic accuracy for clinically significant cases of PCa ( p < 0.002) . Previous investigations have assessed the interobserver agreement of the PI‐RADS final score, with some studies considering the radiologists' experience and others not . For instance, Rosenkrantz et al. compared interobserver agreement among six experienced radiologists, showing moderate reproducibility . Greer et al. found that more experienced radiologists were more often in agreement when assigning PI‐RADS scores compared to less experienced ones . Specifically, moderately experienced readers were more likely to categorize a lesion as indeterminate (PI‐RADS 3) rather than suspicious for csPCa (PI‐RADS 4 and 5) than highly experienced readers. This finding was also confirmed by Mussi et al.  The accuracy of moderately experienced readers using the PI‐RADS system appears to decrease when distinguishing between PI‐RADS ≥ 4 and PI‐RADS 3 lesions. This may be due to the current PIRADSv2 criteria for distinguishing PI‐RADS 3 from PI‐RADS 4 not being sufficiently adequate for less experienced readers, causing difficulty in differentiating between intermediate (PI‐RADS 3) and high suspicion (PI‐RADS 4) lesions. The discordance in agreement for lesion detection (74%) and scoring (58%) may also be attributed to the ambiguity in assessing these lesions . This indicates a critical area for improvement in the next version of PI‐RADS, particularly regarding the clarity of evaluation criteria for less experienced readers. In our study, we lack information about the experience of each radiologist at the evaluated centers, nor is it our goal to define the cutoff that would make a specialist “experienced” in assigning PI‐RADS scores. Some literature suggests that radiologists should have reported at least 100 expert‐supervised prostate mpMRI scans to be considered experienced . However, our study indicates that academic centers tend to assign higher numerical PI‐RADS scores compared to nonacademic centers. Additionally, the risk of diagnosing csPCa in patients with PI‐RADS > 3 was significantly higher in academic centers. This may suggest that PI‐RADS scoring in academic centers reflects a more accurate lesion characterization. A contributing factor could be the level of experience of the radiologists, or alternatively, the difference may be attributed to the equipment used. In fact, we observed that mpMRI in academic centers was more frequently performed with 3T machines, although this difference was not statistically significant. While our data suggest a potential difference in lesion characterization, we acknowledge that, without specific information on the radiologists' experience across different centers, this remains a hypothesis. Regardless of whether this is the cause, there is still a disparity between centers that aligns with findings reported in other studies. For proper standardization, such disparities should not occur. The results of our study may be influenced by certain limitations. The prospective, single‐center design limits the generalizability of our findings. Additionally, the mpMRI images from one group were not reassessed by the other, preventing evaluation of inter‐reader agreement. Moreover, we do not have data on the radiologists' experience who evaluated the images in nonacademic centers, which could further impact the consistency of the mpMRI evaluations. Using biopsy samples could also be a limitation due to potential under‐sampling or technical errors during biopsy. However, using radical prostatectomy specimens could introduce selection bias, as almost all patients would have csPCa, which does not reflect a typical clinical scenario. 

Conclusion Our study highlights the variability in PI‐RADS score assignments between different centers, a discrepancy that has been well‐documented in the literature. While a PI‐RADS score > 3 assigned by an academic center appears more frequently associated with csPCa, this variability underscores the differences in csPCa detection across centers based on mpMRI findings. These findings suggest the need for further efforts toward standardizing PI‐RADS scoring to reduce disparities and enhance diagnostic consistency across all centers. 

Internal board approved the study. All procedures were performed in accordance with the principles of the Declaration of Helsinki. Consent to participate was obtained from all individual participants included in the study. 

Consent for publication has been obtained from all individuals whose data, including individual details, images, or videos, are presented in this manuscript. 

The authors declare no conflicts of interest. 

