OBJECTIVE: To determine the role of dynamic contrast-enhanced (DCE) MRI-radiomics in predicting the International Society of Urological Pathology Grade Group (ISUP-GG) in therapy-naïve prostate cancer (PCa) patients.
METHODS: In this ethics review board-approved retrospective study on two prospective clinical trials between 2017 and 2020, 73 men with suspected/confirmed PCa were included. All participants underwent multiparametric MRI. On MRI, dominant lesions (per PI-RADS) were identified. DCE-MRI radiomic features were extracted from the segmented volumes following the image biomarker standardisation initiative (IBSI) guidelines through 14 time points. Histopathology evaluation on the cognitive-fusion targeted biopsies was set as the reference standard. Univariate regression was done to evaluate potential predictors across all calculated features. Random forest imputation was used for multivariate modelling.
RESULTS: 73 index lesions were reviewed. Histopathology revealed 28, 16, 13 and 16 lesions with ISUP-GG-Negative/1/2, ISUP-GG-3, ISUP-GG-4 and ISUP-GG-5, respectively. From the extracted features, total lesion enhancement (TLE), minimum enhancement intensity and Grey-Level Run Length Matrix (GLRLM) were the most significantly different parameters among ISUP-GGs (Neg/1/2 vs 3/4 vs 5). 16 features with significant cross-sectional associations with ISUP-GGs entered the multivariate analysis. The final DCE partitioning model used only four features (lesion sphericity, TLE, GLRLM and Grey-Level Zone Length Matrix). For the binarized diagnosis (ISUP-GG≤2 vs ISUP-GG>2), the accuracy reached 81%.
CONCLUSIONS: DCE-MRI radiomics might be used as a non-invasive tool for aiding pathological grade group prediction in therapy-naïve PCa patients, potentially adding complementary information to PI-RADS for supporting tailored diagnostic pathways and treatment planning.

BACKGROUND: To test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP).
METHODS: Relying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan-Meier survival analyses and multivariable Cox regression models addressed BCR after RP.
RESULTS: Of 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6).
CONCLUSIONS: Compared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up.

BACKGROUND: Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. This passage aims to preliminarily evaluate the relationship between the zonal heterogeneity of PCa quantitatively assessed by bpMRI and pathological risk stratification of the primary lesion.
METHODS: This prospective study was conducted from January 2019 to February 2023. A total of 113 PCa patients whose bpMRI data indicated that the lesions located in only 1 single zone of the prostate were selected. A transrectal ultrasound and MRI-targeted biopsy were performed to verify the bpMRI results, and then radical prostatectomy (RP) was performed in 3 weeks after the biopsy. The high-risk (HR) group was defined as ISUP grades ≥ 3. Binary regression was performed to evaluate if the zonal heterogeneity could be an independent predictor of the HR group. The receiver operator characteristic (ROC) curve was performed to analyze the added value of zonal location in predicting the HR group.
RESULTS: PSA, T staging, and ISUP grades, incidence of positive surgical margins were significantly lower in the TZ PCa, and the ADCmin, and ADCmean values in the TZ PCa were significantly higher (all P < .01). The zonal heterogeneity could independently predict the HR group patients (OR: 5.170 [1.663-16.067], P = .005) and improve the predicting efficiency of HR patients (AUC 0.824, 95% CI, 0.741-0.889).
CONCLUSIONS: BpMRI could quantitively assess the zonal heterogeneity of PCa precisely and increase the predicting efficacy of HR patients, which can provide better help for clinical individualized treatment.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Intraductal carcinoma of the prostate (IDC-P) is a distinct tumor type characterized by an expansile growth of atypical glandular epithelial cells within pre-existing prostate glands and ducts and has significant implications on clinical outcomes and patient management. There is an agreement that isolated IDC-P should not be graded, and IDC-P should be reported with a comment on its clinical significance. However, whether IDC-P should be factored into Grade Group (GG) in the presence of concurrent prostate cancer (PCa) has been debated vigorously. The contradicting opinions were promulgated when the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathologists (ISUP) published their recommendations for this issue. When IDC-P is present with PCa, the ISUP recommends incorporating it in the GG for the entire case, whereas the GUPS recommends excluding it from the final GG. Consequently, pathologists and clinicians are faced with the conundrum of conflicting recommendations. In this review article, the authors evaluate the magnitude of discrepant GG between the two grading methods, explore the rationales behind the differing views of the two urological societies, present the current reporting practices for IDC-P, and propose a provisional and pragmatic guide to alleviate the dilemma of which recommendation to follow.

Prostate cancer is one of the most common tumors among the male population. Magnetic resonance imaging (MRI), standardized by the PI-RADS version 2.1 scoring system, has a fundamental role in detecting prostate cancer and evaluating its aggressiveness. Diffusion-weighted imaging sequences and apparent diffusion coefficient values, in particular, are considered fundamental for the detection and characterization of lesions. In 2016 the International Society of Urological Pathology introduced a new anatomopathological 5-grade scoring system for prostate cancer. The aim of this study is to evaluate the correlation between quantitative apparent diffusion coefficient values (ADC) derived from diffusion-weighted imaging (DWI) sequences and the International Society of Urological Pathology (ISUP) and PI-RADS groups. Our retrospective study included 143 patients with 154 suspicious lesions, observed on prostate magnetic resonance imaging and compared with the histological results of the biopsy. We observed that ADC values can aid in discriminating between not clinically significant (ISUP 1) and clinically significant (ISUP 2-5) prostate cancers. In fact, ADC values were lower in ISUP 5 lesions than in negative lesions. We also found a correlation between ADC values and PI-RADS groups; we noted lower ADC values in the PI-RADS 5 and PI-RADS 4 groups than in the PI-RADS 3 group. In conclusion, quantitative apparent diffusion coefficient values can be useful to assess the aggressiveness of prostate cancer.

This study aimed to assess the correlation among the peak intensity (PI) values of quantitative parameters, microvessel density (MVD), microvessel maturity, and International Society of Urological Pathology (ISUP) grades in biopsy specimens from prostate cancer (PCa) patients. The study population included PCa patients who underwent targeted and systematic biopsy, without radiation or chemohormonal therapy before biopsy. Contrast-enhanced transrectal ultrasonography (CE-TRUS) was performed in all patients before biopsy. Contrast-enhancement patterns and PI values of quantitative parameters were observed. Tumor tissue samples were immunostained for CD31 expression. MVD, microvessel maturity, and ISUP grades were determined in prostate biopsy specimens. Based on the contrast enhancement patterns of prostate lesions, 16 patients were assigned to a low-enhancement group and 45 to a high-enhancement group. The number of mature vessels, MVD, mature vessel index, and ISUP grades were all higher in the high-enhancement group than in the low-enhancement group (all P < 0.05). The immature vessel index was lower in the high-enhancement group than in the low-enhancement group (P < 0.05). The PI value was positively correlated with the number of mature vessels (r = 0.372). In conclusion, enhancement patterns on CE-TRUS can reflect microvessel maturity in PCa. The PI value was positively correlated with the number of mature vessels.

Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG. The most significantly affected biological processes in the samples were also identified, so that they may be further studied in the search for new potential therapeutic targets for the categories of PCa under consideration. The highest predictive potential was found with the EEF1A1P5, RPLP0P6, ZNF483, CIBAR1, HECTD2, OGN, and CLIC4 genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa-Gleason Score 7 (groups 2 and 3 according to the ISUP classification)-on the basis of which the LPL, MYC, and TWIST1 genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation.

OBJECTIVE: To compare the correlation of Gleason score (GS) and ISUP grade determined by prostate biopsies (PBx) and radical prostatectomy (RP) specimens according to the biopsy technique: ultrasound randomised (RBx) vs. MRI/ultrasound fusion targeted (TBx).
METHODS: Between March 2013 and June 2018, we retrospectively included patients who underwent RP for prostate cancer (PCa) histopathologically proven by RBx and/or TBx. All patients had a prebiopsy MRI by a single radiologist (using PI-RADS score), then transrectal RBx (12cores, blinded to MRI lesions) and TBx (2-4 cores/target) with elastic MRI/ultrasound fusion (UroStation™, Koelis, Grenoble, France). Histological findings were compared: PBx vs. RP.
RESULTS: One hundred and four patients underwent RP after RBx and/or TBx. ISUP concordance rate was better with the association RBx+TBx 49% (51/104) vs. 43.3% with TBx (P=0.07) and 43.3% with RBx (P=0.13). With RBx, 50% of the patients were downgraded (52/104) against 42.3% (44/104) with TBx (P=0.088). The association RBx+TBx significantly decreased the rate of downgrading of the ISUP score compared to the ISUP score of RP 35.6% (37/104) vs. RBx (50%, P=0.0001) and vs. TBx (42.3%, P=0.016).
CONCLUSIONS: In half of cases, the ISUP score was underestimated in RBx compared to RP specimens. Adding TBx to RBx significantly reduced downgrading. The combination of both biopsy techniques appeared to be the best protocol to get closer to ISUP score and GS of the RP specimens.
METHODS: C.

OBJECTIVE: Although active surveillance (AS) is recommended for low- to favorable intermediate-risk prostate cancer (PCa), risk of upgrading at radical prostatectomy (RP) is not negligible. Available studies based on systematic transrectal ultrasound biopsy might not be applicable to contemporary cohorts diagnosed with MRI-targeted biopsy (TB). The aim of the present study is to explore rates and risk factors for adverse outcomes (AO) at RP in patients with ISUP ≤ 2 PCa detected at TB with concomitant systematic biopsy (SB).
METHODS: Multicenter, retrospective analysis of 475 consecutive patients with ISUP ≤ 2 PCa at MRI-TB + SB is treated with RP. AO were defined as ISUP upgrading, adverse pathology (upgrading to ISUP ≥ 3 and/or ≥ pT3 at RP, and/or pN1) (AP) or biochemical recurrence (BCR) in men with follow-up (n = 327).
RESULTS: The rate of ISUP upgrading, upgrading ≥ 3, and AP were 39%, 21%, and 43%. Compared to ISUP2, men with ISUP1 PCa had a higher rate of overall upgrading (27 vs. 67%, p < 0.001), but less upgrading to ≥ 3 (27 vs. 10%, p < 0.001). AP was more common when ISUP2 was detected with a combined MRI-TB + SB approach compared to considering TB (p = 0.02) or SB (p = 0.01) alone. PSA, PSA density, PI-RADS, ISUP at TB, overall biopsy ISUP and EAU classification were predictors of upgrading to ISUP ≥ 3 and AP. The 1 year BCR-free survival was 94% with no differences in BCR rates between subgroups.
CONCLUSIONS: Upgrading in ISUP ≤ 2 PCa remains prevalent even in men diagnosed in the MRI era. The use of MRI-TB with concomitant SB allows for the accurate identification of ISUP2 PCa and predicts the risk of AO at RP.