Low cancer yield in PI-RADS 3 upgraded to 4 by dynamic contrast-enhanced MRI: is it time to reconsider scoring categorization?

OBJECTIVES: To evaluate MRI diagnostic performance in detecting clinically significant prostate cancer (csPCa) in peripheral-zone PI-RADS 4 lesions, comparing those with clearly restricted diffusion (DWI-score 4), and those with equivocal diffusion pattern (DWI-score 3) and positive dynamic contrast-enhanced (DCE) MRI. METHODS: This observational prospective study enrolled 389 men referred to MRI and, if positive (PI-RADS 3 with PSA-density [PSAD] ≥ 0.15 ng/mL/mL, 4 and 5), to MRI-directed biopsy. Lesions with DWI-score 3 and positive DCE were classified as "PI-RADS 3up," instead of PI-RADS 4. Univariable and multivariable analyses were implemented to determine features correlated to csPCa detection. RESULTS: Prevalence of csPCa was 14.5% and 53.3% in PI-RADS categories 3up and 4, respectively (p < 0.001). MRI showed a sensitivity of 100.0%, specificity 40.9%, PPV 46.5%, NPV 100.0%, and accuracy 60.9% for csPCa detection. Modifying the threshold to consider MRI positive and to indicate biopsy (same as previously described, but PI-RADS 3up only when associated with elevated PSAD), the sensitivity changed to 93.9%, specificity 57.2%, PPV 53.0%, NPV 94.8%, and accuracy 69.7%. Age (p < 0.001), PSAD (p < 0.001), positive DWI (p < 0.001), and PI-RADS score (p = 0.04) resulted in independent predictors of csPCa. CONCLUSIONS: Most cases of PI-RADS 3up were false-positives, suggesting that upgrading peripheral lesions with DWI-score 3 to PI-RADS 4 because of positive DCE has a detrimental effect on MRI accuracy, decreasing the true prevalence of csPCa in the PI-RADS 4 category. PI-RADS 3up should not be upgraded and directed to biopsy only if associated with increased PSAD. KEY POINTS: • As per PI-RADS v2.1 recommendations, in case of a peripheral zone lesion with equivocal diffusion-weighted imaging (DWI score 3), but positive dynamic contrast-enhanced (DCE) MRI, the overall PI-RADS score should be upgraded to 4. • The current PI-RADS recommendation of upgrading PI-RADS 3 lesions of the peripheral zone to PI-RADS 4 because of positive DCE decreased clinically significant prostate cancer detection rate in our series. • According to our results, the most accurate threshold for setting indication to prostate biopsy is PI-RADS 3 or PI-RADS 3 with positive DCE both associated with increased PSA density.

Convolutional Neural Networks for Automated Classification of Prostate Multiparametric Magnetic Resonance Imaging Based on Image Quality.

BACKGROUND: Prostate magnetic resonance imaging (MRI) is technically demanding, requiring high image quality to reach its full diagnostic potential. An automated method to identify diagnostically inadequate images could help optimize image quality. PURPOSE: To develop a convolutional neural networks (CNNs) based analysis pipeline for the classification of prostate MRI image quality. STUDY TYPE: Retrospective. SUBJECTS: Three hundred sixteen prostate mpMRI scans and 312 men (median age 67). FIELD STRENGTH/SEQUENCE: A 3 T; fast spin echo T2WI, echo planar imaging DWI, ADC, gradient-echo dynamic contrast enhanced (DCE). ASSESSMENT: MRI scans were reviewed by three genitourinary radiologists (V.P., M.D.M., S.C.) with 21, 12, and 5 years of experience, respectively. Sequences were labeled as high quality (Q1) or low quality (Q0) and used as the reference standard for all analyses. STATISTICAL TESTS: Sequences were split into training, validation, and testing sets (869, 250, and 120 sequences, respectively). Inter-reader agreement was assessed with the Fleiss kappa. Following preprocessing and data augmentation, 28 CNNs were trained on MRI slices for each sequence. Model performance was assessed on both a per-slice and a per-sequence basis. A pairwise t-test was performed to compare performances of the classifiers. RESULTS: The number of sequences labeled as Q0 or Q1 was 38 vs. 278 for T2WI, 43 vs. 273 for DWI, 41 vs. 275 for ADC, and 38 vs. 253 for DCE. Inter-reader agreement was almost perfect for T2WI and DCE and substantial for DWI and ADC. On the per-slice analysis, accuracy was 89.95% ± 0.02% for T2WI, 79.83% ± 0.04% for DWI, 76.64% ± 0.04% for ADC, 96.62% ± 0.01% for DCE. On the per-sequence analysis, accuracy was 100% ± 0.00% for T2WI, DWI, and DCE, and 92.31% ± 0.00% for ADC. The three best algorithms performed significantly better than the remaining ones on every sequence (P-value < 0.05). DATA CONCLUSION: CNNs achieved high accuracy in classifying prostate MRI image quality on an individual-slice basis and almost perfect accuracy when classifying the entire sequences. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

The learning curve in bladder MRI using VI-RADS assessment score during an interactive dedicated training program.

OBJECTIVE: The purpose of the study was to evaluate the effect of an interactive training program on the learning curve of radiology residents for bladder MRI interpretation using the VI-RADS score. METHODS: Three radiology residents with minimal experience in bladder MRI served as readers. They blindly evaluated 200 studies divided into 4 subsets of 50 cases over a 3-month period. After 2 months, the first subset was reassessed, resulting in a total of 250 evaluations. An interactive training program was provided and included educational lessons and case-based practice. The learning curve was constructed by plotting mean agreement as the ratio of correct evaluations per batch. Inter-reader agreement and diagnostic performance analysis were performed with kappa statistics and ROC analysis. RESULTS: As for the VI-RADS scoring agreement, the kappa differences between pre-training and post-training evaluation of the same group of cases were 0.555 to 0.852 for reader 1, 0.522 to 0.695 for reader 2, and 0.481 to 0.794 for reader 3. Using VI-RADS ≥ 3 as cut-off for muscle invasion, sensitivity ranged from 84 to 89% and specificity from 91 to 94%, while the AUCs from 0.89 (95% CI:0.84, 0.94) to 0.90 (95% CI:0.86, 0.95). Mean evaluation time decreased from 5.21 ± 1.12 to 3.52 ± 0.69 min in subsets 1 and 5. Mean grade of confidence improved from 3.31 ± 0.93 to 4.21 ± 0.69, in subsets 1 and 5. CONCLUSION: An interactive dedicated education program on bladder MRI and the VI-RADS score led to a significant increase in readers' diagnostic performance over time, with a general improvement observed after 100-150 cases. KEY POINTS: • After the first educational lesson and 100 cases were interpreted, the concordance on VI-RADS scoring between the residents and the experienced radiologist was significantly higher. • An increase in the grade of confidence was experienced after 100 cases. • We found a decrease in the evaluation time after 150 cases.

Biparametric prostate MRI: impact of a deep learning-based software and of quantitative ADC values on the inter-reader agreement of experienced and inexperienced readers.

OBJECTIVE: To investigate the impact of an artificial intelligence (AI) software and quantitative ADC (qADC) on the inter-reader agreement, diagnostic performance, and reporting times of prostate biparametric MRI (bpMRI) for experienced and inexperienced readers. MATERIALS AND METHODS: A total of 170 multiparametric MRI (mpMRI) of patients with suspicion of prostate cancer (PCa) were retrospectively reviewed by one experienced and one inexperienced reader three times, following a wash-out period. First, only the bpMRI sequences, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) sequences, and apparent diffusion coefficient (ADC) maps, were used. Then, bpMRI and quantitative ADC values were used. Lastly, bpMRI and the AI software were used. Inter-reader agreement between the two readers and between each reader and the mpMRI original reports was calculated. Detection rates and reporting times were calculated for each group. RESULTS: Inter-reader agreement with respect to mpMRI was moderate for bpMRI, Quantib, and qADC for both the inexperienced (weighted k of 0.42, 0.45, and 0.41, respectively) and the experienced radiologists (weighted k of 0.44, 0.46, and 0.42, respectively). Detection rate of PCa was similar between the inexperienced (0.24, 0.26, and 0.23) and the experienced reader (0.26, 0.27 and 0.27), for bpMRI, Quantib, and qADC, respectively. Reporting times were lower for Quantib (8.23, 7.11, and 9.87 min for the inexperienced reader and 5.62, 5.07, and 6.21 min for the experienced reader, for bpMRI, Quantib, and qADC, respectively). CONCLUSIONS: AI and qADC did not have a significant impact on the diagnostic performance of both readers. The use of Quantib was associated with lower reporting times.

A novel pathway to detect muscle-invasive bladder cancer based on integrated clinical features and VI-RADS score on MRI: results of a prospective multicenter study.

PURPOSE: To determine the clinical, pathological, and radiological features, including the Vesical Imaging-Reporting and Data System (VI-RADS) score, independently correlating with muscle-invasive bladder cancer (BCa), in a multicentric national setting. METHOD AND MATERIALS: Patients with BCa suspicion were offered magnetic resonance imaging (MRI) before trans-urethral resection of bladder tumor (TURBT). According to VI-RADS, a cutoff of ≥ 3 or ≥ 4 was assumed to define muscle-invasive bladder cancer (MIBC). Trans-urethral resection of the tumor (TURBT) and/or cystectomy reports were compared with preoperative VI-RADS scores to assess accuracy of MRI for discriminating between non-muscle-invasive versus MIBC. Performance was assessed by ROC curve analysis. Two univariable and multivariable logistic regression models were implemented including clinical, pathological, radiological data, and VI-RADS categories to determine the variables with an independent effect on MIBC. RESULTS: A final cohort of 139 patients was enrolled (median age 70 [IQR: 64, 76.5]). MRI showed sensitivity, specificity, PPV, NPV, and accuracy for MIBC diagnosis ranging from 83-93%, 80-92%, 67-81%, 93-96%, and 84-89% for the more experienced readers. The area under the curve (AUC) was 0.95 (0.91-0.99). In the multivariable logistic regression model, the VI-RADS score, using both a cutoff of 3 and 4 (P < .0001), hematuria (P = .007), tumor size (P = .013), and concomitant hydronephrosis (P = .027) were the variables correlating with a bladder cancer staged as ≥ T2. The inter-reader agreement was substantial (k = 0.814). CONCLUSIONS: VI-RADS assessment scoring proved to be an independent predictor of muscle-invasiveness, which might implicate a shift toward a more aggressive selection approach of patients' at high risk of MIBC, according to a novel proposed predictive pathway.

Preoperative detection of Vesical Imaging-Reporting and Data System (VI-RADS) score 5 reliably identifies extravesical extension of urothelial carcinoma of the urinary bladder and predicts significant delayed time to cystectomy: time to reconsider the need for primary deep transurethral resection of bladder tumour in cases of locally advanced disease?

OBJECTIVES: (I) To determine Vesical Imaging-Reporting and Data System (VI-RADS) score 5 accuracy in predicting locally advanced bladder cancer (BCa), so as to potentially identify those patients who could avoid the morbidity of deep transurethral resection of bladder tumour (TURBT) in favour of histological sampling-TUR prior to radical cystectomy (RC). (II) To explore the predictive value of VI-RADS score 5 on time-to-cystectomy (TTC) outcomes. PATIENTS AND METHODS: We retrospectively reviewed patients' ineligible or refusing cisplatin-based combination neoadjuvant chemotherapy who underwent multiparametric magnetic resonance imaging (mpMRI) of the bladder prior to staging TURBT followed by RC for muscle-invasive BCa. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for VI-RADS score 5 vs. score 2-4 cases to assess the accuracy of mpMRI for extravesical BCa detection (≥pT3). VI-RADS score performance was assessed by receiver operating characteristics curve analysis. A Κ statistic was calculated to estimate mpMRI and pathological diagnostic agreement. The risk of delayed TTC (i.e. time from initial BCa diagnosis of >3 months) was assessed using multivariable logistic regression model. RESULTS: A total of 149 T2-T4a, cN0-M0 patients (VI-RADS score 5, n = 39 vs VI-RADS score 2-4, n = 110) were examined. VI-RADS score 5 demonstrated sensitivity, specificity, PPV and NPV, in detecting extravesical disease of 90.2% (95% confidence interval [CI] 84-94.3), 98.1% (95% CI 94-99.6), 94.9% (95% CI 89.6-97.6) and 96.4% (95% CI 91.6-98.6), respectively. The area under the curve was 94.2% (95% CI 88.7-99.7) and inter-reader agreement was excellent (Κinter 0.89). The mean (SD) TTC was 4.2 (2.3) and 2.8 (1.1) months for score 5 vs 2-4, respectively (P < 0.001). VI-RADS score 5 was found to independently increase risk of delayed TTC (odds ratio 2.81, 95% CI 1.20-6.62). CONCLUSION: The VI-RADS is valid and reliable in differentiating patients with extravesical disease from those with muscle-confined BCa before TURBT. Detection of VI-RADS score 5 was found to predict significant delay in TTC independently from other clinicopathological features. In the future, higher VI-RADS scores could potentially avoid the morbidity of extensive primary resections in favour of sampling-TUR for histology. Further prospective, larger, and multi-institutional trials are required to validate clinical applicability of our findings.

Utilization of imaging for staging in bladder cancer: is there a role for MRI or PET-computed tomography?

PURPOSE OF REVIEW: Accurate staging of bladder cancer is essential to guide appropriate management. In this review, we discuss the principles, applications and performance of multiparametric MRI (mpMRI) and PET-computer tomography (PET-CT) for local and distant staging of bladder cancer. RECENT FINDINGS: Bladder mpMRI has a high diagnostic performance in local staging of bladder cancer, superior to other imaging modalities. It can accurately differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC), as well as ≤T2 from ≥T3 stages. mpMRI can be used to assess pelvic lymph nodes, although its sensitivity is relatively low. For the assessment of the upper urinary tract, CT urography is the imaging modality of choice. magnetic resonance urography is a viable alternative to CT in selected cases. Although PET-CT is accurate for nodal and distant staging of bladder cancer, there is no clear evidence on its superior diagnostic performance compared with contrast-enhanced CT. SUMMARY: mpMRI is the most accurate imaging modality for local staging of bladder cancer, capable to accurately distinguish MIBC from NMIBC. Nodal and distant staging relies primarily on contrast-enhanced CT.

Seeing is Believing: State of the Art Imaging of Bladder Cancer.

Imaging plays an important role in bladder cancer (BCa) diagnostic work-up. Ultrasound achieves an intermediate sensitivity in detecting urinary tract alterations and is considered a suboptimal imaging technique in diagnosis of BCa. CT urography accurately detects BCa in patients presenting with hematuria Multiparametric MRI achieves a very high rate of BCa detection and helps with accurate staging of patients; however, this modality is still not widely supported by international guidelines. The main applications of MRI are local tumor staging and differentiation between non-muscle-invasive BCa and muscle-invasive BCa. These applications led to development of Vesical Imaging-Reporting and Data System (VI-RADS) scoring system. The VI-RADS scoring system was developed in the setting of post-resection of primary bladder tumor and instillation of intravesical Bacillus Calmette-Guerin therapy; however validation of this system in the post-treatment setting showed promising results. The high risk of BCa recurrence leads to its application in the assessment of response to therapy and for disease surveillance after treatment. MRI is rapidly becoming a leading imaging modality in BCa diagnostic workup, assessment of response to therapies and for longitudinal surveillance, and plays an important role in BCa surgical and radiation therapy treatment planning.

MRI-directed biopsy for primary detection of prostate cancer in a population of 223 men: MRI In-Bore vs MRI-transrectal ultrasound fusion-targeted techniques.

OBJECTIVES: To compare the detection rates of overall prostate cancer (PCa) and clinically significant PCa (csPCa) and the median percentage of cancer per biopsy core between MRI-guided In-bore and MRI-TRUS fusion-targeted biopsy (TBx). METHODS: In this retrospective study, 223 patients who underwent prostate multiparametric MRI (mpMRI) and subsequent MR-directed biopsy were included. For PCa and csPCa detection rate (DR), contingency tables were tested via the Pearson's chi-squared to explore the variance of the outcome distribution. The percentage of cancer per biopsy core was tested with a two-tailed Mann-Withney test. RESULTS: One hundred and seventeen and 106 patients underwent MRI-TRUS fusion or MRI In-bore TBx, respectively. 402 MRI biopsy targets were identified, of which 206 (51.2%) were biopsied with the MRI-TRUS TBx and 196 (48.8%) with the MRI In-bore TBx technique. Per-patient PCa and csPCa detection rates were 140/223 (62.8%) and 97/223 (43.5%), respectively. PCa-DR was 73/117 (62.4%) and 67/106 (63.2%) for MRI-TRUS and MRI In-Bore TBx (p = 0.9), while csPCa detection rate reached 50/117 (42.7%) and 47/106 (44.3%), respectively (p = 0.81). The median per-patient percentage of malignant tissue within biopsy cores was 50% (IQR: 27-65%) for PCa and 60% (IQR: 35-68%) for csPCa, with a statistically significant difference between the techniques. CONCLUSION: No statistically significant difference in the detection rate of MRI In-bore and MRI-TRUS fusion TBx was found. MRI In-bore TBx showed higher per-core percentage of malignant cells. ADVANCES IN KNOWLEDGE: MRI In-bore biopsy might impact risk stratification and patient management considering the higher per-core percentage of malignant cells, especially for patients eligible for active surveillance or focal therapy.

The future direction of imaging in prostate cancer: MRI with or without contrast injection.

BACKGROUND: Multiparametric MRI (mpMRI) is the "state of the art" management tool for patients with suspicion of prostate cancer (PCa). The role of non-contrast MRI is investigated to move toward a more personalized, less invasive, and highly cost-effective PCa diagnostic workup. OBJECTIVE: To perform a non-systematic review of the existing literature to highlight strength and flaws of performing non-contrast MRI, and to provide a critical overview of the international scientific production on the topic. MATERIALS AND METHODS: Online databases (Medline, PubMed, and Web of Science) were searched for original articles, systematic review and meta-analysis, and expert opinion papers. RESULTS: Several investigations have shown comparable diagnostic accuracy of biparametric (bpMRI) and mpMRI for the detection of PCa. The advantage of abandoning contrast-enhanced sequences improves operational logistics, lowering costs, acquisition time, and side effects. The main limitations of bpMRI are that most studies comparing non-contrast with contrast MRI come from centers with high expertise that might not be reproducible in the general community setting; besides, reduced protocols might be insufficient for estimation of the intra- and extra-prostatic extension and regional disease. The mentioned observations suggest that low-quality mpMRI for the general population might represent the main shortage to overcome. DISCUSSION: Non-contrast MRI future trends are likely represented by PCa screening and the application of artificial intelligence (AI) tools. PCa screening is still a controversial topic; bpMRI has become one of the most promising diagnostic applications, as it is a more sensitive test for PCa early detection, compared to serum PSA level test. Also, AI applications and radiomic have been the object of several studies investigating PCa detection using bpMRI, showing encouraging results. CONCLUSION: Today, the accessibility to MRI for early detection of PCa is a priority. Results from prospective, multicenter, multireader, and paired validation studies are needed to provide evidence supporting its role in the clinical practice.

Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection.

The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen's Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78-0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader's experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; p= 0.003 and 0.036, SE: 0.009; p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.