Is MRI ready to replace biopsy during active surveillance?

Active surveillance (AS) is a conservative management option recommended for patients diagnosed with low-risk prostate cancer (PCa) and selected cases with intermediate-risk PCa. The adoption of prostate MRI in the primary diagnostic setting has sparked interest in its application during AS. This review aims to examine the role and performance of multiparametric MRI (mpMRI) across the entire AS pathway, from initial stratification to follow-up, also relative to the utilization of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria. Given the high negative predictive value of mpMRI in detecting clinically significant PCa (csPCa), robust evidence supports its use in patient selection and risk stratification at the time of diagnosis or confirmatory biopsy. However, conflicting results have been observed when using MRI in evaluating disease progression during follow-up. Key areas requiring clarification include addressing the clinical significance of MRI-negative csPCa, optimizing MRI quality, determining the role of biparametric MRI (bpMRI) or mpMRI protocols, and integrating artificial intelligence (AI) for improved performance. CLINICAL RELEVANCE STATEMENT: MRI plays an essential role in the selection, stratification, and follow up of patients in active surveillance (AS) for prostate cancer. However, owing to existing limitations, it cannot fully replace biopsies in the context of AS. KEY POINTS: Multiparametric MRI (mpMRI) has become a crucial tool in active surveillance (AS) for prostate cancer (PCa). Conflicting results have been observed regarding multiparametric MRI efficacy in assessing disease progression. Standardizing MRI-guided protocols will be critical in addressing current limitations in active surveillance for prostate cancer.

Artificial intelligence and radiologists in prostate cancer detection on MRI (PI-CAI): an international, paired, non-inferiority, confirmatory study.

BACKGROUND: Artificial intelligence (AI) systems can potentially aid the diagnostic pathway of prostate cancer by alleviating the increasing workload, preventing overdiagnosis, and reducing the dependence on experienced radiologists. We aimed to investigate the performance of AI systems at detecting clinically significant prostate cancer on MRI in comparison with radiologists using the Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS 2.1) and the standard of care in multidisciplinary routine practice at scale. METHODS: In this international, paired, non-inferiority, confirmatory study, we trained and externally validated an AI system (developed within an international consortium) for detecting Gleason grade group 2 or greater cancers using a retrospective cohort of 10 207 MRI examinations from 9129 patients. Of these examinations, 9207 cases from three centres (11 sites) based in the Netherlands were used for training and tuning, and 1000 cases from four centres (12 sites) based in the Netherlands and Norway were used for testing. In parallel, we facilitated a multireader, multicase observer study with 62 radiologists (45 centres in 20 countries; median 7 [IQR 5-10] years of experience in reading prostate MRI) using PI-RADS (2.1) on 400 paired MRI examinations from the testing cohort. Primary endpoints were the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) of the AI system in comparison with that of all readers using PI-RADS (2.1) and in comparison with that of the historical radiology readings made during multidisciplinary routine practice (ie, the standard of care with the aid of patient history and peer consultation). Histopathology and at least 3 years (median 5 [IQR 4-6] years) of follow-up were used to establish the reference standard. The statistical analysis plan was prespecified with a primary hypothesis of non-inferiority (considering a margin of 0·05) and a secondary hypothesis of superiority towards the AI system, if non-inferiority was confirmed. This study was registered at ClinicalTrials.gov, NCT05489341. FINDINGS: Of the 10 207 examinations included from Jan 1, 2012, through Dec 31, 2021, 2440 cases had histologically confirmed Gleason grade group 2 or greater prostate cancer. In the subset of 400 testing cases in which the AI system was compared with the radiologists participating in the reader study, the AI system showed a statistically superior and non-inferior AUROC of 0·91 (95% CI 0·87-0·94; p<0·0001), in comparison to the pool of 62 radiologists with an AUROC of 0·86 (0·83-0·89), with a lower boundary of the two-sided 95% Wald CI for the difference in AUROC of 0·02. At the mean PI-RADS 3 or greater operating point of all readers, the AI system detected 6·8% more cases with Gleason grade group 2 or greater cancers at the same specificity (57·7%, 95% CI 51·6-63·3), or 50·4% fewer false-positive results and 20·0% fewer cases with Gleason grade group 1 cancers at the same sensitivity (89·4%, 95% CI 85·3-92·9). In all 1000 testing cases where the AI system was compared with the radiology readings made during multidisciplinary practice, non-inferiority was not confirmed, as the AI system showed lower specificity (68·9% [95% CI 65·3-72·4] vs 69·0% [65·5-72·5]) at the same sensitivity (96·1%, 94·0-98·2) as the PI-RADS 3 or greater operating point. The lower boundary of the two-sided 95% Wald CI for the difference in specificity (-0·04) was greater than the non-inferiority margin (-0·05) and a p value below the significance threshold was reached (p<0·001). INTERPRETATION: An AI system was superior to radiologists using PI-RADS (2.1), on average, at detecting clinically significant prostate cancer and comparable to the standard of care. Such a system shows the potential to be a supportive tool within a primary diagnostic setting, with several associated benefits for patients and radiologists. Prospective validation is needed to test clinical applicability of this system. FUNDING: Health~Holland and EU Horizon 2020.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer.

BACKGROUND: The IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual's cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1-<5%), intermediate-risk (5-<20%), and high-risk (≥20%) groups. OBJECTIVE: To externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. DESIGN, SETTING, AND PARTICIPANTS: Prospective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. RESULTS AND LIMITATIONS: There were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. CONCLUSIONS: The IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. PATIENT SUMMARY: We previously developed a calculator that predicts patients' risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

An international survey of contemporary practices towards fertility assessment and preservation in patients undergoing radical inguinal orchidectomy for testicular cancer.

Objective: The study aims to assess current international clinician attitudes, practices and barriers towards fertility assessment and preservation in patients undergoing radical inguinal orchidectomy (RIO) for testicular cancer. Materials and methods: An international online survey of urologists and urologists in training who perform RIO for testicular cancer was developed by the British Association of Urological Surgeons (BAUS) Sections of Andrology and Oncology and the British Urology Researchers in Surgical Training (BURST). The recruitment process used social media and the emailing lists of national urological societies. Responses were collected between 10/02/2021 and 31/05/2021 and stored using password-protected Research Electronic Data Capture (REDCap) database software. The primary outcome was the proportion of urologists who routinely offer semen cryopreservation prior to RIO. The study was reported according to the Checklist for Reporting Results of Internet E-Surveys platform. Results: A total of 393 respondents took part in the online survey; of these, the majority were from the United Kingdom (65.9%), with the remaining international respondents (34.1%) from six different continents, which included 45 different countries. Of the respondents, 57.1% reported that they would routinely offer semen cryopreservation to all patients undergoing RIO for testicular cancer. In addition, 36.0% of urologists routinely performed pre-operative semen analysis, and 22.1% routinely performed pre-operative testicular serum hormone profile. Of the respondents, 14.4% performed expedited RIO within 48 h; 31.2% of respondents reported that they considered no delay to RIO to allow for semen cryopreservation to be acceptable. Conclusions: A significant proportion of international urologists do not offer pre-operative fertility assessment and preservation in men undergoing RIO for testicular cancer. Surgery is performed in an expedited fashion within 1 week in the majority of patients. Urologists perceive there to be a lack of access and availability to fertility services, and that delay to RIO to allow for fertility preservation is often not acceptable.

PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI.

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. CLINICAL RELEVANCE STATEMENT: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. KEY POINTS: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI.

Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Radical Prostatectomy for Nonmetastatic Prostate Cancer in Renal Transplant Recipients: Outcomes for a Large Contemporary Cohort and a Matched Comparison to Patients Without a Transplant.

BACKGROUND AND OBJECTIVE: It is unknown whether renal transplant receipt (RTR) status can affect perioperative and oncological outcomes of radical prostatectomy (RP). Our aim was to evaluate oncological and functional outcomes of RTR patients treated with RP for cN0M0 prostate cancer (PCa) via comparison with a no-RTR cohort. METHODS: RTR patients who had undergone RP at seven European institutions during 2001-2022 were identified. A multi-institutional cohort of no-RTR patients treated with RP during 2004-2022 served as the comparator group. Propensity score matching (PSM) at a ratio of 1:4 was used to match no-RTR patients to the RTR cohort according to age, prostate-specific antigen, and final pathology features. We used Kaplan-Meier plots and multivariable Cox, logistic, and Poisson log-linear regression models to test the outcomes of interest. KEY FINDINGS AND LIMITATIONS: After PSM, we analyzed data for 102 RTR and 408 no-RTR patients. RTR patients experienced higher estimated blood loss (EBL), longer length of hospital stay (LOS) and time to catheter removal, higher postoperative complication rates, and a lower continence recovery rate (all p < 0.001). On multivariable analyses, RTR independently predicted unfavorable operative time (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.18-1.25), LOS (OR 1.57, 95% CI 1.32-1.86), EBL (OR 2.24, 95% CI 2.18-2.30), and time to catheter removal (OR 1.93, 95% CI 1.68-2.21), but not complications or continence recovery. There were no significant differences for any oncological outcomes (biochemical recurrence, local or systemic progression) between the RTR and no-RTR groups. While no PCa deaths were recorded, the overall mortality rate was significantly higher in the RTR group (17% vs 0.5%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although RP is feasible for RTR patients, the procedure poses non-negligible surgical challenges, with longer operative time and LOS and higher EBL, but no major differences in terms of complications and continence recovery. The RTR group had similar oncological outcomes to the no-RTR group but significantly higher overall mortality related to causes other than PCa. Therefore, careful selection for RP is required among candidates with previous RTR. PATIENT SUMMARY: Removal of the prostate for prostate cancer is possible in patients who have had a kidney transplant, and cancer control outcomes are comparable to those for the general population. However, transplant patients have a higher risk of death from causes other than prostate cancer and the prostate surgery is likely to be more challenging.

PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer.

BACKGROUND AND OBJECTIVE: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty. METHODS: A panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1-9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring. KEY FINDINGS AND LIMITATIONS: Participants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of 'X' for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9). CONCLUSIONS AND CLINICAL IMPLICATIONS: The updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS. PATIENT SUMMARY: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations are used in clinical practice and research to guide the interpretation and reporting of magnetic resonance imaging for patients on active surveillance for prostate cancer. An international panel has updated these recommendations, clarified the areas of uncertainty, and highlighted the areas for further research.

Nonsurgical Interventions to Prevent Disease Progression in Prostate Cancer Patients on Active Surveillance: A Systematic Review and Meta-analysis.

CONTEXT: Active surveillance (AS) is a standard of care for patients with low-risk and selected intermediate-risk prostate cancer (PCa). Nevertheless, there is a lack of summary evidence on how to impact disease trajectory during AS. OBJECTIVE: To assess which interventions prevent PCa progression effectively during AS. EVIDENCE ACQUISITION: We queried PubMed, Scopus, and Web of Science databases to identify studies examining the impact of interventions aimed at slowing disease progression during AS. The primary endpoint was PCa progression, the definition of which must have included pathological upgrading. The secondary endpoint included treatment toxicities. EVIDENCE SYNTHESIS: We identified 22 studies, six randomized controlled trials and 16 observational studies, which analyzed the association between different interventions and PCa progression during AS. The interventions considered in the studies included 5-alpha reductase inhibitors (5-ARIs), statins, diet, exercise, chlormadinone, fexapotide triflutate (FT), enzalutamide, coffee, vitamin D3, and PROSTVAC. We found that administration of 5-ARIs was associated with improved progression-free survival (PFS; hazard ratio: 0.59; 95% confidence interval 0.48-0.72), with no increased toxicity signals. Therapies such as vitamin D3, chlormadinone, FT, and enzalutamide have shown some efficacy. However, these anticancer drugs have been associated with treatment-related adverse events in up to 88% of patients. CONCLUSIONS: The use of 5-ARIs in PCa patients on AS is associated with longer PFS. However, for the other interventions, it is difficult to draw clear conclusions based on the weak available evidence. PATIENT SUMMARY: Patients with prostate cancer managed with active surveillance (AS) who are treated with 5-alpha reductase inhibitors have a lower risk of disease progression, with minimal adverse events. Other interventions require more studies to determine their efficacy and safety profile in men on AS.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Patient enrolment began in March 2022, with recruitment expected to take 36 mo. PATIENT SUMMARY: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.

Global Variation in Magnetic Resonance Imaging Quality of the Prostate.

Background High variability in prostate MRI quality might reduce accuracy in prostate cancer detection. Purpose To prospectively evaluate the quality of MRI scanners taking part in the quality control phase of the global PRIME (Prostate Imaging Using MRI ± Contrast Enhancement) trial using the Prostate Imaging Quality (PI-QUAL) standardized scoring system, give recommendations on how to improve the MRI protocols, and establish whether MRI quality could be improved by these recommendations. Materials and Methods In the prospective clinical trial (PRIME), for each scanner, centers performing prostate MRI submitted five consecutive studies and the MRI protocols (phase I). Submitted data were evaluated in consensus by two expert genitourinary radiologists using the PI-QUAL scoring system that evaluates MRI diagnostic quality using five points (1 and 2 = nondiagnostic; 3 = sufficient; 4 = adequate, 5 = optimal) between September 2021 and August 2022. Feedback was provided for scanners not achieving a PI-QUAL 5 score, and centers were invited to resubmit new imaging data using the modified protocol (phase II). Descriptive comparison of outcomes was made between the MRI scanners, feedback provided, and overall PI-QUAL scores. Results In phase I, 41 centers from 18 countries submitted a total of 355 multiparametric MRI studies from 71 scanners, with nine (13%) scanners achieving a PI-QUAL score of 3, 39 (55%) achieving a score of 4, and 23 (32%) achieving a score of 5. Of the 48 (n = 71 [68%]) scanners that received feedback to improve, the dynamic contrast-enhanced sequences were those that least adhered to the Prostate Imaging Reporting and Data System, version 2.1, criteria (44 of 48 [92%]), followed by diffusion-weighted imaging (20 of 48 [42%]) and T2-weighted imaging (19 of 48 [40%]). In phase II, 36 centers from 17 countries resubmitted revised studies, resulting in a total of 62 (n = 64 [97%]) scanners with a final PI-QUAL score of 5. Conclusion Substantial variation in global prostate MRI acquisition parameters as a measure of quality was observed, particularly with DCE sequences. Basic evaluation and modifications to MRI protocols using PI-QUAL can lead to substantial improvements in quality. Clinical trial registration no. NCT04571840 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almansour and Chernyak in this issue.

Outcomes of a Diagnostic Pathway for Prostate Cancer Based on Biparametric MRI and MRI-Targeted Biopsy Only in a Large Teaching Hospital.

BACKGROUND: Diagnostic pathways for prostate cancer (PCa) balance detection rates and burden. MRI impacts biopsy indication and strategy. METHODS: A prospectively collected cohort database (N = 496) of men referred for elevated PSA and/or abnormal DRE was analyzed. All underwent biparametric MRI (3 Tesla scanner) and ERSPC prostate risk-calculator. Indication for biopsy was PIRADS ≥ 3 or risk-calculator ≥ 20%. Both targeted (cognitive-fusion) and systematic cores were combined. A hypothetical full-MRI-based pathway was retrospectively studied, omitting systematic biopsies in: (1) PIRADS 1-2 but risk-calculator ≥ 20%, (2) PIRADS ≥ 3, receiving targeted biopsy-cores only. RESULTS: Significant PCa (GG ≥ 2) was detected in 120 (24%) men. Omission of systematic cores in cases with PIRADS 1-2 but risk-calculator ≥ 20%, would result in 34% less biopsy indication, not-detecting 7% significant tumors. Omission of systematic cores in PIRADS ≥ 3, only performing targeted biopsies, would result in a decrease of 75% cores per procedure, not detecting 9% significant tumors. Diagnosis of insignificant PCa dropped by 52%. PCa undetected by targeted cores only, were ipsilateral to MRI-index lesions in 67%. CONCLUSIONS: A biparametric MRI-guided PCa diagnostic pathway would have missed one out of six cases with significant PCa, but would have considerably reduced the number of biopsy procedures, cores, and insignificant PCa. Further refinement or follow-up may identify initially undetected cases. Center-specific data on the performance of the diagnostic pathway is required.

The ARTS (Avoiding Risks of Thrombosis and Bleeding in Surgery) Trial: Lessons Learnt in Setting Up an International Multicentre Clinical Trial of an Investigational Medicinal Product in the UK.

We describe our experience in setting up the UK arm of the ARTS trial and highlight regulatory and funding challenges in relation to an international multicentre setting for an investigational medicinal product.

The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions.

OBJECTIVE: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. METHODS: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. RESULTS: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12-20) and 18 mo (IQR 12-21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. CONCLUSIONS: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx.

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.