Multiparametric MRI and 18F-PSMA-1007 PET/CT for the Detection of Clinically Significant Prostate Cancer.

Background Multiparametric MRI (mpMRI) is effective for detecting prostate cancer (PCa); however, there is a high rate of equivocal Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions and false-positive findings. Purpose To investigate whether fluorine 18 (18F) prostate-specific membrane antigen (PSMA) 1007 PET/CT after mpMRI can help detect localized clinically significant PCa (csPCa), particularly for equivocal PI-RADS 3 lesions. Materials and Methods This prospective study included participants with elevated prostate-specific antigen (PSA) levels referred for prostate mpMRI between September 2020 and February 2022. 18F-PSMA-1007 PET/CT was performed within 30 days of mpMRI and before biopsy. PI-RADS category and level of suspicion (LOS) were assessed. PI-RADS 3 or higher lesions at mpMRI and/or LOS 3 or higher lesions at 18F-PSMA-1007 PET/CT underwent targeted biopsies. PI-RADS 2 or lower and LOS 2 or lower lesions were considered nonsuspicious and were monitored during a 1-year follow-up by means of PSA testing. Diagnostic accuracy was assessed, with histologic examination serving as the reference standard. International Society of Urological Pathology (ISUP) grade 2 or higher was considered csPCa. Results Seventy-five participants (median age, 67 years [range, 52-77 years]) were assessed, with PI-RADS 1 or 2, PI-RADS 3, and PI-RADS 4 or 5 groups each including 25 participants. A total of 102 lesions were identified, of which 80 were PI-RADS 3 or higher and/or LOS 3 or higher and therefore underwent targeted biopsy. The per-participant sensitivity for the detection of csPCa was 95% and 91% for mpMRI and 18F-PSMA-1007 PET/CT, respectively, with respective specificities of 45% and 62%. 18F-PSMA-1007 PET/CT was used to correctly differentiate 17 of 26 PI-RADS 3 lesions (65%), with a negative and positive predictive value of 93% and 27%, respectively, for ruling out or detecting csPCa. One additional significant and one insignificant PCa lesion (PI-RADS 1 or 2) were found at 18F-PSMA-1007 PET/CT that otherwise would have remained undetected. Two participants had ISUP 2 tumors without PSMA uptake that were missed at PET/CT. Conclusion 18F-PSMA-1007 PET/CT showed good sensitivity and moderate specificity for the detection of csPCa and ruled this out in 93% of participants with PI-RADS 3 lesions. Clinical trial registration no. NCT04487847 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Turkbey in this issue.

The association between patient and disease characteristics, and the risk of disease progression in patients with prostate cancer on active surveillance.

PURPOSE: The objective of this study was to identify and assess patient and disease characteristics associated with an increased risk of disease progression in men with prostate cancer on active surveillance. METHODS: We studied patients with low-risk (ISUP GG1) or favorable intermediate-risk (ISUP GG2) PCa. All patients had at least one repeat biopsy. Disease progression was the primary outcome of this study, based on pathological upgrading. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the association between covariates and disease progression. RESULTS: In total, 240 men were included, of whom 198 (82.5%) were diagnosed with low-risk PCa and 42 (17.5%) with favorable intermediate-risk PCa. Disease progression was observed in 42.9% (103/240) of men. Index lesion > 10 mm (HR = 2.85; 95% CI 1.74-4.68; p < 0.001), MRI (m)T-stage 2b/2c (HR = 2.52; 95% CI 1.16-5.50; p = 0.02), highest PI-RADS score of 5 (HR 3.05; 95% CI 1.48-6.28; p = 0.002) and a higher PSA level (HR 1.06; 95% CI 1.01-1.11; p = 0.014) at baseline were associated with disease progression on univariate analysis. Multivariate analysis showed no significant baseline predictors of disease progression. CONCLUSION: In AS patients with low-risk or favorable intermediate-risk PCa, diameter of index lesion, MRI (m)T-stage, height of the PI-RADS score and the PSA level at baseline are significant predictors of disease progression to first repeat biopsy.

The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

BACKGROUND: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. PURPOSE: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. MATERIALS AND METHODS: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. RESULTS: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. CONCLUSIONS: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Subnodal Correspondence of PSMA Expression and USPIO-MRI in Metastatic Pelvic Lymph Nodes in Prostate Cancer.

OBJECTIVES: Two advanced imaging modalities used to detect lymph node (LN) metastases in prostate cancer patients are prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography and ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). As these modalities use different targets, a subnodal comparison is needed to interpret both their correspondence and their differences. The aim of this explorative study was to compare ex vivo 111In-PSMA µSPECT images with high-resolution 7 T USPIO µMR images and histopathology of resected LN specimens from prostate cancer patients to assess the degree of correspondence at subnodal level. MATERIALS AND METHODS: Twenty primary prostate cancer patients who underwent pelvic LN dissection were included and received USPIO contrast and 111In-PSMA. A total of 41 LNs of interest (LNOIs) were selected for ex vivo imaging based on γ-probe detection or palpation. µSPECT and µMRI acquisition were performed immediately after resection. Overlay of µSPECT images on MR images was performed, and the level of correspondence (LoC) between µSPECT and µMR findings was assessed according to a 4-point Likert classification scheme. RESULTS: Forty-one LNOIs could be matched to an LN on ex vivo µMRI. Coregistration of µSPECT and USPIO-enhanced water-selective multigradient echo MR images was successful for all 41 LNOIs. Ninety percent of the lesions showed excellent correspondence regarding the presence of metastatic tissue and affected subnodal site (LoC 4; 37/41). In only 1 of 41 LNOIs, a small metastasis was misclassified by both techniques. Three LNOIs were classified as LoC 3 (7%) and 1 LNOI as LoC 2. All LoC 2 and LoC 3 lesions had PSMA-expressing metastases on final histopathology. CONCLUSIONS: Coregistration of µSPECT and USPIO-µMRI showed excellent subnodal correspondence in the majority (90%) of LNs. Ex vivo imaging may thus help localize small cancer deposits within resected LNs and could contribute to improved interpretation of in vivo imaging of LNs.

Radiomics based automated quality assessment for T2W prostate MR images.

PURPOSE: The guidelines for prostate cancer recommend the use of MRI in the prostate cancer pathway. Due to the variability in prostate MR image quality, the reliability of this technique in the detection of prostate cancer is highly variable in clinical practice. This leads to the need for an objective and automated assessment of image quality to ensure an adequate acquisition and hereby to improve the reliability of MRI. The aim of this study is to investigate the feasibility of Blind/referenceless image spatial quality evaluator (Brisque) and radiomics in automated image quality assessment of T2-weighted (T2W) images. METHOD: Anonymized axial T2W images from 140 patients were scored for quality using a five-point Likert scale (low, suboptimal, acceptable, good, very good quality) in consensus by two readers. Images were dichotomized into clinically acceptable (very good, good and acceptable quality images) and clinically unacceptable (low and suboptimal quality images) in order to train and verify the model. Radiomics and Brisque features were extracted from a central cuboid volume including the prostate. A reduced feature set was used to fit a Linear Discriminant Analysis (LDA) model to predict image quality. Two hundred times repeated 5-fold cross-validation was used to train the model and test performance by assessing the classification accuracy, the discrimination accuracy as receiver operating curve - area under curve (ROC-AUC), and by generating confusion matrices. RESULTS: Thirty-four images were classified as clinically unacceptable and 106 were classified as clinically acceptable. The accuracy of the independent test set (mean ± standard deviation) was 85.4 ± 5.5%. The ROC-AUC was 0.856 (0.851 - 0.861) (mean; 95% confidence interval). CONCLUSIONS: Radiomics AI can automatically detect a significant portion of T2W images of suboptimal image quality. This can help improve image quality at the time of acquisition, thus reducing repeat scans and improving diagnostic accuracy.

Incidence of significant prostate cancer after negative MRI and systematic biopsy in the FUTURE trial.

OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strategies is warranted.

Quality checkpoints in the MRI-directed prostate cancer diagnostic pathway.

Multiparametric MRI of the prostate is now recommended as the initial diagnostic test for men presenting with suspected prostate cancer, with a negative MRI enabling safe avoidance of biopsy and a positive result enabling MRI-directed sampling of lesions. The diagnostic pathway consists of several steps, from initial patient presentation and preparation to performing and interpreting MRI, communicating the imaging findings, outlining the prostate and intra-prostatic target lesions, performing the biopsy and assessing the cores. Each component of this pathway requires experienced clinicians, optimized equipment, good inter-disciplinary communication between specialists, and standardized workflows in order to achieve the expected outcomes. Assessment of quality and mitigation measures are essential for the success of the MRI-directed prostate cancer diagnostic pathway. Quality assurance processes including Prostate Imaging-Reporting and Data System, template biopsy, and pathology guidelines help to minimize variation and ensure optimization of the diagnostic pathway. Quality control systems including the Prostate Imaging Quality scoring system, patient-level outcomes (such as Prostate Imaging-Reporting and Data System MRI score assignment and cancer detection rates), multidisciplinary meeting review and audits might also be used to provide consistency of outcomes and ensure that all the benefits of the MRI-directed pathway are achieved.

How Advanced Imaging Will Guide Therapeutic Strategies for Patients with Newly Diagnosed Prostate Cancer in the Years to Come.

In recent years, clinical use of novel advanced imaging modalities in prostate cancer detection, staging, and therapy has intensified and is currently reforming clinical guidelines. In the future, advanced imaging technologies will continue to develop and become even more accurate, which will offer new opportunities for improving patient selection, surgical treatment, and radiotherapy, with the potential to guide prostate cancer therapy.

Implications of the European Association of Urology Recommended Risk Assessment Algorithm for Early Prostate Cancer Detection.

The 2021 European Association of Urology recommendations for early prostate cancer detection included a risk-based algorithm. Risk assessment methods are proposed to prevent excessive use of prostate magnetic resonance imaging (MRI) and biopsy, simultaneously reducing overdiagnosis and overtreatment. However, the clinical implications of sequential use of risk assessment tests have not yet been properly assessed. We provide an appraisal of the recommended algorithm and evaluate its outcomes in a contemporary prospective study population of biopsy-naïve men. To increase the effectiveness in cases of limited MRI capacity, we show that use of the Rotterdam Prostate Cancer Risk Calculator-3 for pre-MRI risk stratification could avoid more than one-third of MRI examinations. After prostate MRI, use of either the Prostate Imaging-Reporting and Data System (PI-RADS) score or a risk model including MRI outcome as a variable could avoid six out of ten prostate biopsies while maintaining high sensitivity. However, implementation in health care systems requires due consideration of the access to and quality of diagnostic resources, as well as cost-effectiveness. Patient summary: We evaluated the European Association of Urology risk-based strategy for early prostate cancer detection. Risk assessment before magnetic resonance imaging (MRI) using a risk calculator or prostate-specific antigen (PSA) density could reduce MRI demands and overdiagnosis of insignificant cancers. Risk assessment using prostate MRI results could avoid 60% of prostate biopsies while maintaining prostate cancer detection rates.The European Association of Urology (EAU) recently published its current position and recommendations on prostate-specific antigen (PSA) testing [1]. On the basis of the literature and expert opinion, a risk-based algorithm for early detection of prostate cancer (PCa) was proposed. The guideline recommends stratifying men with PSA ≥3 ng/ml as either "low risk", for whom magnetic resonance imaging (MRI) can be avoided, or "intermediate and high risk", for whom prostate MRI should be performed as a basis for further diagnostic decisions. Strategies must be developed to use health care resources efficiently and to reduce unnecessary morbidity, anxiety, and costs of diagnostics. However, any paradigm shift inevitably leads to a paucity of research data. As a result, there is still debate regarding which men can safely avoid an initial MRI but are subjected to clinical follow-up, and which men must undergo an immediate MRI. The authors proposed four methods for risk assessment: (1) family history; (2) PSA velocity; (3) PSA density; and (4) risk calculators. It must be stressed that the availability and quality of prostate MRI in each situation should be considered when using these pre-MRI risk assessment tools. We discuss in brief the proposed risk assessment methods including MRI and assess potential outcomes in a contemporary population.

Diagnostic Accuracy and Observer Agreement of the MRI Prostate Imaging for Recurrence Reporting Assessment Score.

Background Prostate cancer local recurrence location and extent must be determined in an accurate and timely manner. Because of the lack of a standardized MRI approach after whole-gland treatment, a panel of international experts recently proposed the Prostate Imaging for Recurrence Reporting (PI-RR) assessment score. Purpose To determine the diagnostic accuracy of PI-RR for detecting local recurrence in patients with biochemical recurrence (BCR) after radiation therapy (RT) or radical prostatectomy (RP) and to evaluate the interreader variability of PI-RR scoring. Materials and Methods This retrospective observational study included patients who underwent multiparametric MRI between September 2016 and May 2021 for BCR after RT or RP. MRI scans were analyzed, and a PI-RR score was assigned independently by four radiologists. The reference standard was defined using histopathologic findings, follow-up imaging, or clinical response to treatment. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess PI-RR performance for each reader. The intraclass correlation coefficient was used to determine interreader agreement. Results A total of 100 men were included: 48 patients after RT (median age, 76 years [IQR, 70-82 years]) and 52 patients after RP (median age, 70 years [IQR, 66-74 years]). After RT, with PI-RR of 3 or greater as a cutoff (assigned when recurrence is uncertain), diagnostic performance ranges were 71%-81% sensitivity, 74%-93% specificity, 71%-89% PPV, 79%-86% NPV, and 77%-88% accuracy across the four readers. After RP, with PI-RR of 3 or greater as a cutoff, performance ranges were 59%-83% sensitivity, 87%-100% specificity, 88%-100% PPV, 66%-80% NPV, and 75%-85% accuracy. The intraclass correlation coefficient was 0.87 across the four readers for both the RT and RP groups. Conclusion MRI scoring with the Prostate Imaging for Recurrence Reporting assessment provides structured, reproducible, and accurate evaluation of local recurrence after definitive therapy for prostate cancer. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Haider in this issue. An earlier incorrect version appeared online. This article was corrected on May 11, 2022.

A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Ferumoxtran-10-enhanced 3-T Magnetic Resonance Angiography of Pelvic Arteries: Initial Experience.

BACKGROUND: Patients with renal impairment cannot undergo angiography because iodine and gadolinium contrast agents are contraindicated. Iron-containing ultrasmall superparamagnetic iron oxide particles, such as ferumoxtran-10, are not contraindicated in these patients. Thus, patients with renal failure can still undergo angiography with ferumoxtran-10. OBJECTIVE: To evaluate the visibility of pelvic vessels with magnetic resonance angiography (MRA) using ferumoxtran-10 as contrast agent. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and eighty-one patients diagnosed with primary or recurrent prostate cancer underwent pelvic ferumoxtran-10 MRA. Eleven anatomical pelvic-vessel segments per patient were evaluated using qualitative and quantitative criteria for image quality (IQ), vessel visibility (VV), and the contrast-to-noise ratio (CNR). INTERVENTION: Ferumoxtran-10-enhaced MRA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: IQ, VV, and CNR were assessed on a 5-point scale for each data set/vessel segment (very poor, poor, moderate, good, and excellent). RESULTS AND LIMITATIONS: IQ was good to excellent for 98.2% of the data sets and VV was good to excellent for 97.7% of all vessel segments. The mean CNR for all segments was 88.13 (standard deviation 4.22). Contrast bolus imaging cannot be performed with this technique, so it is impossible to visualize the arterial or venous phase separately. The timing of contrast administration is also a limitation, with MRA performed 1 d after contrast infusion. CONCLUSIONS: Ferumoxtran-10 MRA showed excellent image quality and visibility for pelvic vessels. In addition, the homogeneity of the intraluminal contrast was superior. Patients with preterminal or terminal renal function can benefit from ferumoxtran-10 MRA if visualization of their pelvic vessels is required. PATIENT SUMMARY: Magnetic resonance imaging of blood vessels using a contrast agent called ferumoxtran-10 is a promising technique for patients with impaired kidney function, as it provides high-quality visualization of blood vessels in the pelvis.

PI-QUAL v.1: the first step towards good-quality prostate MRI.

KEY POINTS: • It is mandatory to evaluate the image quality of a prostate MRI scan, and to mention this quality in the report. • PI-QUAL v1 is an essential starting tool to standardize the evaluation of the quality of prostate MR-images as objectively as possible. • PI-QUAL will step by step develop into a reliable quality assessment tool to ensure that the first step of the MRI pathway is as accurate as possible.

Risk Stratification and Artificial Intelligence in Early Magnetic Resonance Imaging-based Detection of Prostate Cancer.

Magnetic resonance imaging (MRI) has transformed the diagnostic pathway for prostate cancer and now plays an upfront role before prostate biopsies. If a suspicious lesion is found on MRI, the subsequent biopsy can be targeted. A sharp increase is expected in the number of men who will undergo prostate MRI. The challenge is to provide good image quality and diagnostic accuracy while meeting the demands of the expected higher workload. A possible solution to this challenge is to include a suitable risk stratification tool before imaging. Other solutions, such as smarter and shorter MRI protocols, need to be explored. For most of these solutions, artificial intelligence (AI) can play an important role. AI applications have the potential to improve the diagnostic quality of the prostate MRI pathway and speed up the work. PATIENT SUMMARY: The use of prostate magnetic resonance imaging (MRI) for diagnosis of prostate cancer is increasing. Risk stratification of patients before imaging and the use of shorter scan protocols can help in managing MRI resources. Artificial intelligence can also play a role in automating some tasks.

Radiomic combination of spatial and temporal features extracted from DCE-MRI for prostate cancer detection.

Multi-parametric MRI is part of the standard prostate cancer (PCa) diagnostic protocol. Recent imaging guidelines (PI-RADS v2) downgraded the value of Dynamic Contrast-Enhanced (DCE)-MRI in the diagnosis of PCa. A purely qualitative analysis of the DCE-MRI time series, as it is generally done by radiologists, might indeed overlook information on the microvascular architecture and function. In this study, we investigate the discriminative power of quantitative imaging features derived from texture and pharmacokinetic analysis of DCE-MRI. In 605 regions of interest (benign and malignant tissue) delineated in 80 patients, we found through independent cross-validation that a subset of quantitative spatial and temporal features extracted from DCE-MRI and incorporated in machine learning classifiers obtains a good diagnostic performance (AUC = 0.80-0.86) in distinguishing malignant from benign regions.Clinical Relevance- These findings highlight the underlying potential of quantitative DCE-derived radiomic features in identifying PCa by MRI.

Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer: the BULLSEYE trial.

BACKGROUND: The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial. CHANGES IN METHODS AND MATERIALS: Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; "Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer" and is now partly supported by Advanced Accelerator Applications, a Novartis Company. CONCLUSIONS: We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced. TRIAL REGISTRATION: ClinicalTrials.gov NCT04443062 . First posted: June 23, 2020.

A European Model for an Organised Risk-stratified Early Detection Programme for Prostate Cancer.

CONTEXT: Overdiagnosis as the argument to stop prostate cancer (PCa) screening is less valid since the introduction of new technologies such as risk calculators (RCs) and magnetic resonance imaging (MRI). These new technologies result in fewer unnecessary biopsy procedures and fewer cases of both overdiagnosis and underdetection. Therefore, we can now adequately respond to the growing and urgent need for a structured risk assessment to detect PCa early. OBJECTIVE: To provide expert discussion on the existing evidence for a previously published risk-stratified strategy regarding an organised population-based early detection programme for PCa. EVIDENCE ACQUISITION: The proposed algorithm for early detection of PCa emerged from expert consensus by the authors based on available evidence derived from a nonsystematic review of the current literature using Medline/PubMed, Cochrane Library database, ClinicalTrials.gov, ISRCTN Registry, and the European Association of Urology guidelines on PCa. EVIDENCE SYNTHESIS: Although not confirmed by the highest level of evidence, current literature and guidelines point towards an algorithm for early detection of PCa that starts with risk-based prostate-specific antigen (PSA) testing, followed by multivariable risk stratification with RCs. All men who are classified to be at intermediate and high risk are then offered prostate MRI. The combined data from RCs and MRI results can be used to select men for prostate biopsy. Low-risk men return to a risk-based safety net that includes individualised PSA-interval tests and, if necessary, repeated MRI. Depending on local availability, the use of the different risk stratification tools may be adapted. CONCLUSIONS: We present a risk-stratified algorithm for an organised population-based early detection programme for clinically significant PCa. Although the proposed strategy has not yet been analysed prospectively, it exploits and may even improve the most important available benefits of "PSA-only" screening studies, while at the same time reduces unnecessary biopsies and overdiagnosis by using new risk stratification tools. PATIENT SUMMARY: This paper presents a personalised strategy that enables selective early detection of prostate cancer by combining prostate-specific antigen (interval) testing' prediction models (risk calculators), and magnetic resonance imaging scans. This will likely lead to reduced prostate cancer-related morbidity and mortality, while reducing the need for prostate biopsy and limiting overdiagnosis.

Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men.

BACKGROUND: Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of "unnecessary" prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. METHODS: This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥-2.8. Decision curve analysis (DCA) was performed to assess clinical utility. RESULTS: Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. CONCLUSIONS: SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.