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.

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.

ESR Essentials: using the right scoring system in prostate MRI-practice recommendations by ESUR.

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. KEY POINTS: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol.

INTRODUCTION: Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer. METHODS AND ANALYSIS: The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes. ETHICS AND DISSEMINATION: The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management. TRIAL REGISTRATION NUMBER: NCT05532930.

Diagnostic Utility of Artificial Intelligence-assisted Transperineal Biopsy Planning in Prostate Cancer Suspected Men: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone. METHODS: A total of 262 consecutive men scheduled for TPB at our referral centre were analysed. Reported PI-RADS lesions and an US Food and Drug Administration-cleared CAD tool were used for TPB planning. PI-RADS and CAD lesions were targeted on TPB, while four (interquartile range: 2-5) systematic biopsies were taken. The outcomes were the (1) proportion of csPCa (grade group ≥2) and (2) number of targeted lesions and false-positive rate. Performance was tested using free-response receiver operating characteristic curves and the exact Fisher-Yates test. KEY FINDINGS AND LIMITATIONS: Overall, csPCa was detected in 56% (146/262) of men, with sensitivity of 92% and 97% (p = 0.007) for PI-RADS- and CAD-directed TPB, respectively. In 4% (10/262), csPCa was detected solely by CAD-directed biopsies; in 8% (22/262), additional csPCa lesions were detected. However, the number of targeted lesions increased by 54% (518 vs 336) and the false-positive rate doubled (0.66 vs 1.39; p = 0.009). Limitations include biopsies only for men at clinical/radiological suspicion and no multidisciplinary review of MRI before biopsy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The tested CAD tool for TPB planning improves csPCa detection at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences. PATIENT SUMMARY: The computer-aided diagnosis tool tested for transperineal prostate biopsy planning improves the detection of clinically significant prostate cancer at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences.

Reduction of false positives using zone-specific prostate-specific antigen density for prostate MRI-based biopsy decision strategies.

OBJECTIVES: To develop and test zone-specific prostate-specific antigen density (sPSAD) combined with PI-RADS to guide prostate biopsy decision strategies (BDS). METHODS: This retrospective study included consecutive patients, who underwent prostate MRI and biopsy (01/2012-10/2018). The whole gland and transition zone (TZ) were segmented at MRI using a retrained deep learning system (DLS; nnU-Net) to calculate PSAD and sPSAD, respectively. Additionally, sPSAD and PI-RADS were combined in a BDS, and diagnostic performances to detect Grade Group ≥ 2 (GG ≥ 2) prostate cancer were compared. Patient-based cancer detection using sPSAD was assessed by bootstrapping with 1000 repetitions and reported as area under the curve (AUC). Clinical utility of the BDS was tested in the hold-out test set using decision curve analysis. Statistics included nonparametric DeLong test for AUCs and Fisher-Yates test for remaining performance metrics. RESULTS: A total of 1604 patients aged 67 (interquartile range, 61-73) with 48% GG ≥ 2 prevalence (774/1604) were evaluated. By employing DLS-based prostate and TZ volumes (DICE coefficients of 0.89 (95% confidence interval, 0.80-0.97) and 0.84 (0.70-0.99)), GG ≥ 2 detection using PSAD was inferior to sPSAD (AUC, 0.71 (0.68-0.74)/0.73 (0.70-0.76); p < 0.001). Combining PI-RADS with sPSAD, GG ≥ 2 detection specificity doubled from 18% (10-20%) to 43% (30-44%; p < 0.001) with similar sensitivity (93% (89-96%)/97% (94-99%); p = 0.052), when biopsies were taken in PI-RADS 4-5 and 3 only if sPSAD was ≥ 0.42 ng/mL/cc as compared to all PI-RADS 3-5 cases. Additionally, using the sPSAD-based BDS, false positives were reduced by 25% (123 (104-142)/165 (146-185); p < 0.001). CONCLUSION: Using sPSAD to guide biopsy decisions in PI-RADS 3 lesions can reduce false positives at MRI while maintaining high sensitivity for GG ≥ 2 cancers. CLINICAL RELEVANCE STATEMENT: Transition zone-specific prostate-specific antigen density can improve the accuracy of prostate cancer detection compared to MRI assessments alone, by lowering false-positive cases without significantly missing men with ISUP GG ≥ 2 cancers. KEY POINTS: • Prostate biopsy decision strategies using PI-RADS at MRI are limited by a substantial proportion of false positives, not yielding grade group ≥ 2 prostate cancer. • PI-RADS combined with transition zone (TZ)-specific prostate-specific antigen density (PSAD) decreased the number of unproductive biopsies by 25% compared to PI-RADS only. • TZ-specific PSAD also improved the specificity of MRI-directed biopsies by 9% compared to the whole gland PSAD, while showing identical sensitivity.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.

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.

PI-RADS Upgrading Rules: Impact on Prostate Cancer Detection and Biopsy Avoidance of MRI-Directed Diagnostic Pathways.

BACKGROUND. PI-RADS incorporates rules by which ancillary sequence findings upgrade a dominant score to a higher final category. Evidence on the upgrading rules' impact on diagnostic pathways remains scarce. OBJECTIVE. The purpose of this article was to evaluate the clinical net benefit of the PI-RADS upgrading rules in MRI-directed diagnostic pathways. METHODS. This study was a retrospective analysis of a prospectively maintained clinical registry. The study included patients without known prostate cancer who underwent prostate MRI followed by prostate biopsy from January 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as International Society of Urological Pathology (ISUP) grade group 2 and higher. csPCa detection was compared between dominant (i.e., no upgrade rule applied) and upgraded lesions. Decision-curve analysis was used to compare the net benefit, considering the trade-off of csPCa detection and biopsy avoidance, of MRI-directed pathways in scenarios considering and disregarding PI-RADS upgrading rules. These included a biopsy-all pathway, MRI-focused pathway (no biopsy for PI-RADS ≤ 2), and risk-based pathway (use of PSA density ≥ 0.15 ng/mL2 to select patients with PI-RADS ≤ 3 for biopsy). RESULTS. The sample comprised 716 patients (mean age, 64.9 years; 93 with a PI-RADS ≤ 2 examination, 623 with total of 780 PI-RADS ≥ 3 lesions). Frequencies of csPCa were not significantly different between dominant and upgraded PI-RADS 3 transition zone lesions (20% vs 19%, respectively), dominant and upgraded PI-RADS 4 transition zone lesions (33% vs 26%), and dominant and upgraded PI-RADS 4 peripheral zone lesions (58% vs 45%) (p > .05). In the biopsy-all, per-guideline MRI-focused, MRI-focused disregarding upgrading rules, per-guideline risk-based, and risk-based disregarding upgrading rules pathways, csPCa frequency was 53%, 52%, 51%, 52%, and 48% and biopsy avoidance was 0%, 13%, 16%, 19%, and 25%, respectively. Disregarding upgrading rules yielded 5.5 and 1.9 biopsies avoided per missed csPCa for MRI-focused and risk-based pathways, respectively. At probability thresholds for biopsy selection of 7.5-30.0%, net benefit was highest for the per-guideline risk-based pathway. CONCLUSION. Disregarding PI-RADS upgrading rules reduced net clinical bene fit of the risk-based MRI-directed diagnostic pathway when considering trade-offs between csPCa detection and biopsy avoidance. CLINICAL IMPACT. This study supports the application of PI-RADS upgrading rules to optimize biopsy selection, particularly in risk-based pathways.

Key learning on the promise and limitations of MRI in prostate cancer screening.

MRI retains its ability to reduce the harm of prostate biopsies by decreasing biopsy rates and the detection of indolent cancers in population-based screening studies aiming to find clinically significant prostate cancers. Limitations of low positive predictive values and high reader variability in diagnostic performance require optimisations in patient selection, imaging protocols, interpretation standards, diagnostic thresholds, and biopsy methods. Improvements in diagnostic accuracy could come about through emerging technologies like risk calculators and polygenic risk scores to select men for MRI. Furthermore, artificial intelligence and workflow optimisations focused on streamlining the diagnostic pathway, quality control, and assurance measures will improve MRI variability. CLINICAL RELEVANCE STATEMENT: MRI significantly reduces harm in prostate cancer screening, lowering unnecessary biopsies and minimizing the overdiagnosis of indolent cancers. MRI maintains the effective detection of high-grade cancers, thus improving the overall benefit-to-harm ratio in population-based screenings with or without using serum prostate-specific antigen (PSA) for patient selection. KEY POINTS: • The use of MRI enables the harm reduction benefits seen in individual early cancer detection to be extended to both risk-stratified and non-stratified prostate cancer screening populations. • MRI limitations include a low positive predictive value and imperfect reader variability, which require standardising interpretations, biopsy methods, and integration into a quality diagnostic pathway. • Current evidence is based on one-time point use of MRI in screening; MRI effectiveness in multiple rounds of screening is not well-documented.

How Imaging Advances Are Defining the Future of Precision Radiation Therapy.

Radiation therapy is fundamental in the treatment of cancer. Imaging has always played a central role in radiation oncology. Integrating imaging technology into irradiation devices has increased the precision and accuracy of dose delivery and decreased the toxic effects of the treatment. Although CT has become the standard imaging modality in radiation therapy, the development of recently introduced next-generation imaging techniques has improved diagnostic and therapeutic decision making in radiation oncology. Functional and molecular imaging techniques, as well as other advanced imaging modalities such as SPECT, yield information about the anatomic and biologic characteristics of tumors for the radiation therapy workflow. In clinical practice, they can be useful for characterizing tumor phenotypes, delineating volumes, planning treatment, determining patients' prognoses, predicting toxic effects, assessing responses to therapy, and detecting tumor relapse. Next-generation imaging can enable personalization of radiation therapy based on a greater understanding of tumor biologic factors. It can be used to map tumor characteristics, such as metabolic pathways, vascularity, cellular proliferation, and hypoxia, that are known to define tumor phenotype. It can also be used to consider tumor heterogeneity by highlighting areas at risk for radiation resistance for focused biologic dose escalation, which can impact the radiation planning process and patient outcomes. The authors review the possible contributions of next-generation imaging to the treatment of patients undergoing radiation therapy. In addition, the possible roles of radio(geno)mics in radiation therapy, the limitations of these techniques, and hurdles in introducing them into clinical practice are discussed. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Prostagram magnetic resonance imaging in a screening population: Prostate Imaging-Reporting and Data System or Likert?

OBJECTIVE: To compare biopsy recommendation rates and accuracy of the Prostate Imaging-Reporting and Data System, version 2 (PI-RADSv2) with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within the Imperial Prostate 1 Prostate Cancer Screening Trial Using Imaging (IP1-PROSTAGRAM). PATIENTS AND METHODS: Men aged 50-69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI-RADSv2 (excluding dynamic contrast-enhanced sequence score) and 5-point Likert scores by expert uro-radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥ 3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for Grade Groups (GGs) 1 and ≥ 2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance. RESULTS: A total of 406 men underwent Prostagram MRI. The median (interquartile range) age and prostate-specific antigen level were 57 (53-61) years and 0.91 (0.56-1.74) ng/mL, respectively. At MRI score ≥ 3, more patients were recommended for biopsy based on Likert criteria (94/406; 23%, 95% confidence interval [CI] 19.2%-27.6%) compared to PI-RADSv2 (72/406; 18%, 95% CI 14.2%-21.9%; P = 0.03). For MRI scores ≥ 4, PI-RADSv2 and Likert scales led to 43/406 (11%, 95% CI 7.9%-14.1%) and 35/406 (9%, 95% CI 6.2%-11.9%) men recommended for biopsy (P = 0.40). For GG ≥ 2 detection, PIRADSv2 and Likert detected 22% (95% CI 11.4%-30.8%, 14/72) and 16% (95% CI 9.5%-25.3%, 15/94), respectively (P = 0.56). For GG1 cancers detection these were 11% (95% CI 4.3%-19.6%, seven of 72) vs 11% (95% CI 4.7%-17.8%, nine of 94; P = 1.00). The accuracy of PI-RADSv2 and Likert scale was similar (area under the ROC curve 0.64 vs 0.65, P = 0.95). CONCLUSIONS: In reporting non-contrast-enhanced Prostagram MRI in a screening population, the PI-RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI-RADSv2 or a modified Likert scale or a standalone scoring system should be developed.

The Impact of Positron Emission Tomography Imaging and Tumor Molecular Profiling on Risk Stratification, Treatment Choice, and Oncological Outcomes of Patients with Primary or Relapsed Prostate Cancer: An International Collaborative Review of the Existing Literature.

CONTEXT: The clinical introduction of next-generation imaging methods and molecular biomarkers ("radiogenomics") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation. OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF). EVIDENCE ACQUISITION: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias. EVIDENCE SYNTHESIS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3). CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited. PATIENT SUMMARY: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.

Management of Patients With a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review.

Multiparametric prostate MRI (mpMRI) aids risk stratification of patients with elevated PSA levels. While most clinically significant prostate cancers are detected by mpMRI, insignificant cancers are less evident. Thus, multiple international prostate cancer guidelines now endorse routine use of prostate MRI as a secondary screening test before prostate biopsy. Nonetheless, management of patients with negative mpMRI results (defined as PI-RADS category 1 or 2) remains unclear. This AJR Expert Panel Narrative Review summarizes the available literature on patients with an elevated screening PSA level and a negative prostate mpMRI, and provides guidance for these patients' management. Systematic biopsy should not be routinely performed after a negative mpMRI in patients at average risk but should be considered in patients at high risk. In patients who undergo PSA screening rather than systematic biopsy after negative mpMRI, clear triggers should be established for when to perform a repeat MRI. Patients with negative MRI followed by negative biopsy should follow their healthcare practitioners' preferred guidelines concerning subsequent PSA screening for the patient's risk level. Insufficient high-level data exist to support routine use of adjunctive serum or urine biomarkers, artificial intelligence, or PSMA PET to determine the need for prostate biopsy after negative mpMRI.

Radium-223 in metastatic castration-resistant prostate cancer: whole-body diffusion-weighted magnetic resonance imaging scanning to assess response.

BACKGROUND: Radium-223 is a bone-seeking, ɑ-emitting radionuclide used to treat men with bone metastases from castration-resistant prostate cancer. Sclerotic bone lesions cannot be evaluated using Response Evaluation Criteria in Solid Tumors. Therefore, imaging response biomarkers are needed. METHODS: We conducted a phase 2 randomized trial to assess disease response to radium-223. Men with metastatic castration-resistant prostate cancer and bone metastases were randomly allocated to 55 or 88 kBq/kg radium-223 every 4 weeks for 6 cycles. Whole-body diffusion-weighted magnetic resonance imaging (DWI) was performed at baseline, at cycles 2 and 4, and after treatment. The primary endpoint was defined as a 30% increase in global median apparent diffusion coefficient. RESULTS: Disease response on DWI was seen in 14 of 36 evaluable patients (39%; 95% confidence interval = 23% to 56%), with marked interpatient and intrapatient heterogeneity of response. There was an association between prostate-specific antigen response and MRI response (odds ratio = 18.5, 95% confidence interval = 1.32 to 258, P = .013). Mean administered activity of radium-223 per cycle was not associated with global MRI response (P = .216) but was associated with DWI response using a 5-target-lesion evaluation (P = .007). In 26 of 36 (72%) patients, new bone metastases, not present at baseline, were seen on DWI scans during radium-223 treatment. CONCLUSIONS: DWI is useful for assessment of disease response in bone. Response to radium-223 is heterogeneous, both between patients and between different metastases in the same patient. New bone metastases appear during radium-223 treatment.The REASURE trial is registered under ISRCTN17805587.