New Prostate MRI Scoring Systems (PI-QUAL, PRECISE, PI-RR, and PI-FAB): AJR Expert Panel Narrative Review.

Multiparametric MRI (mpMRI), interpreted using PI-RADS, improves the initial detection of clinically significant prostate cancer (PCa). Prostate MR image quality has increasingly recognized relevance to the use of mpMRI for PCa diagnosis. Additionally, mpMRI is increasingly used in scenarios beyond initial detection, including active surveillance and assessment for local recurrence after prostatectomy, radiation therapy, or focal therapy. Acknowledging these evolving demands, specialized prostate MRI scoring systems beyond PI-RADS have emerged, to address distinct scenarios and unmet needs. Examples include Prostate Imaging Quality (PI-QUAL) for assessment of image quality of mpMRI, Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation (PRECISE) recommendations for evaluation of serial mpMRI examinations during active surveillance, Prostate Imaging for Recurrence Reporting System (PI-RR) for assessment for local recurrence after prostatectomy or radiation therapy, and Prostate Imaging after Focal Ablation (PI-FAB) for assessment for local recurrence after focal therapy. These systems' development and early uptake signal a compelling shift towards prostate MRI standardization in different scenarios, and ongoing research will help refine their roles in practice. This AJR Expert Panel Narrative Review critically examines these new prostate MRI scoring systems (PI-QUAL, PRECISE, PI-RR, and PI-FAB), analyzing the available evidence, delineating current limitations, and proposing solutions for improvement.

Quantitative Prostate MRI, From the AJR Special Series on Quantitative Imaging.

Prostate MRI has traditionally relied on qualitative interpretation. However, quantitative components hold the potential to markedly improve performance. The ADC from DWI is probably the most widely recognized quantitative MRI biomarker and has shown strong discriminatory value for clinically significant prostate cancer (csPCa) as well as for recurrent cancer after treatment. Advanced diffusion techniques, including intravoxel incoherent motion, diffusion kurtosis, diffusion tensor imaging, and specific implementations such as restriction spectrum imaging, purport even better discrimination, but are more technically challenging. The inherent T1 and T2 of tissue also provide diagnostic value, with more advanced techniques deriving luminal water imaging and hybrid-multidimensional MRI. Dynamic contrast-enhanced imaging, primarily using a modified Tofts model, also shows independent discriminatory value. Finally, quantitative size and shape features can be combined with the aforementioned techniques and be further refined using radiomics, texture analysis, and artificial intelligence. Which technique will ultimately find widespread clinical use will depend on validation across a myriad of platforms use-cases.

Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

This corrects the article DOI: 10.1038/nature22364.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

PURPOSE: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368). MATERIALS AND METHODS: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored. RESULTS: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. CONCLUSIONS: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.

Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCE-MRI: Results from a multicenter phantom study.

PURPOSE: To determine the in vitro accuracy, test-retest repeatability, and interplatform reproducibility of T1 quantification protocols used for dynamic contrast-enhanced MRI at 1.5 and 3 T. METHODS: A T1 phantom with 14 samples was imaged at eight centers with a common inversion-recovery spin-echo (IR-SE) protocol and a variable flip angle (VFA) protocol using seven flip angles, as well as site-specific protocols (VFA with different flip angles, variable repetition time, proton density, and Look-Locker inversion recovery). Factors influencing the accuracy (deviation from reference NMR T1 measurements) and repeatability were assessed using general linear mixed models. Interplatform reproducibility was assessed using coefficients of variation. RESULTS: For the common IR-SE protocol, accuracy (median error across platforms = 1.4-5.5%) was influenced predominantly by T1 sample (P < 10-6 ), whereas test-retest repeatability (median error = 0.2-8.3%) was influenced by the scanner (P < 10-6 ). For the common VFA protocol, accuracy (median error = 5.7-32.2%) was influenced by field strength (P = 0.006), whereas repeatability (median error = 0.7-25.8%) was influenced by the scanner (P < 0.0001). Interplatform reproducibility with the common VFA was lower at 3 T than 1.5 T (P = 0.004), and lower than that of the common IR-SE protocol (coefficient of variation 1.5T: VFA/IR-SE = 11.13%/8.21%, P = 0.028; 3 T: VFA/IR-SE = 22.87%/5.46%, P = 0.001). Among the site-specific protocols, Look-Locker inversion recovery and VFA (2-3 flip angles) protocols showed the best accuracy and repeatability (errors < 15%). CONCLUSIONS: The VFA protocols with 2 to 3 flip angles optimized for different applications achieved acceptable balance of extensive spatial coverage, accuracy, and repeatability in T1 quantification (errors < 15%). Further optimization in terms of flip-angle choice for each tissue application, and the use of B1 correction, are needed to improve the robustness of VFA protocols for T1 mapping. Magn Reson Med 79:2564-2575, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono-exponential (GAME) model.

A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R2 (*) mapping with Mono-Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient-echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono-Exponential (GAME) decay model, in the prostate at 3T. Multi-gradient-echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR-guided prostate biopsies. Data were fitted with both ME and GAME models. The information contents of these models were compared using Akaike's information criterion (second order, AICC ), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions of interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R2 (*) approached 40 s(-1) . R2 (*) mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, for example of oxygenation status.

Transperineal in-bore 3-T MR imaging-guided prostate biopsy: a prospective clinical observational study.

PURPOSE: To determine the detection rate, clinical relevance, Gleason grade, and location of prostate cancer ( PCa prostate cancer ) diagnosed with and the safety of an in-bore transperineal 3-T magnetic resonance (MR) imaging-guided prostate biopsy in a clinically heterogeneous patient population. MATERIALS AND METHODS: This prospective retrospectively analyzed study was HIPAA compliant and institutional review board approved, and informed consent was obtained. Eighty-seven men (mean age, 66.2 years ± 6.9) underwent multiparametric endorectal prostate MR imaging at 3 T and transperineal MR imaging-guided biopsy. Three subgroups of patients with at least one lesion suspicious for cancer were included: men with no prior PCa prostate cancer diagnosis, men with PCa prostate cancer who were undergoing active surveillance, and men with treated PCa prostate cancer and suspected recurrence. Exclusion criteria were prior prostatectomy and/or contraindication to 3-T MR imaging. The transperineal MR imaging-guided biopsy was performed in a 70-cm wide-bore 3-T device. Overall patient biopsy outcomes, cancer detection rates, Gleason grade, and location for each subgroup were evaluated and statistically compared by using χ(2) and one-way analysis of variance followed by Tukey honestly significant difference post hoc comparisons. RESULTS: Ninety biopsy procedures were performed with no serious adverse events, with a mean of 3.7 targets sampled per gland. Cancer was detected in 51 (56.7%) men: 48.1% (25 of 52) with no prior PCa prostate cancer , 61.5% (eight of 13) under active surveillance, and 72.0% (18 of 25) in whom recurrence was suspected. Gleason pattern 4 or higher was diagnosed in 78.1% (25 of 32) in the no prior PCa prostate cancer and active surveillance groups. Gleason scores were not assigned in the suspected recurrence group. MR targets located in the anterior prostate had the highest cancer yield (40 of 64, 62.5%) compared with those for the other parts of the prostate (P < .001). CONCLUSION: In-bore 3-T transperineal MR imaging-guided biopsy, with a mean of 3.7 targets per gland, allowed detection of many clinically relevant cancers, many of which were located anteriorly.

3T MR-guided in-bore transperineal prostate biopsy: A comparison of robotic and manual needle-guidance templates.

PURPOSE: To demonstrate the utility of a robotic needle-guidance template device as compared to a manual template for in-bore 3T transperineal magnetic resonance imaging (MRI)-guided prostate biopsy. MATERIALS AND METHODS: This two-arm mixed retrospective-prospective study included 99 cases of targeted transperineal prostate biopsies. The biopsy needles were aimed at suspicious foci noted on multiparametric 3T MRI using manual template (historical control) as compared with a robotic template. The following data were obtained: the accuracy of average and closest needle placement to the focus, histologic yield, percentage of cancer volume in positive core samples, complication rate, and time to complete the procedure. RESULTS: In all, 56 cases were performed using the manual template and 43 cases were performed using the robotic template. The mean accuracy of the best needle placement attempt was higher in the robotic group (2.39 mm) than the manual group (3.71 mm, P < 0.027). The mean core procedure time was shorter in the robotic (90.82 min) than the manual group (100.63 min, P < 0.030). Percentage of cancer volume in positive core samples was higher in the robotic group (P < 0.001). Cancer yields and complication rates were not statistically different between the two subgroups (P = 0.557 and P = 0.172, respectively). CONCLUSION: The robotic needle-guidance template helps accurate placement of biopsy needles in MRI-guided core biopsy of prostate cancer.

Craniocaudal retroperitoneal node length as a risk factor for relapse from clinical stage I testicular germ cell tumor.

OBJECTIVE: The purpose of this study was to investigate whether retroperitoneal craniocaudal nodal length or nodal volume predicts relapse risk in stage I testicular cancer. MATERIALS AND METHODS: We retrospectively reviewed 826 testicular cancer patients. Of these 826 patients, 118 had stage I disease and either less than 2 years of surveillance or retroperitoneal lymph node dissection with no adjuvant chemotherapy. These patients formed our analytic cohort, and 3D nodal volumes and craniocaudal nodal length were measured. Association between relapse risk and craniocaudal nodal length and nodal volume was evaluated using univariable or multivariable logistic regression models adjusted for known prognostic factors. RESULTS: Sixty-six (56%) of 118 patients had nonseminomatous germ cell tumor and 52 (44%) had seminomatous germ cell tumor. Craniocaudal nodal length proved to be an independent risk factor in nonseminomatous germ cell tumors using a multivariable logistic regression model adjusting for other potential known risk factors of embryonal predominance and lymphovascular invasion. For every 3-mm increase in craniocaudal nodal length, the risk of relapse increased by 52% (odds ratio [OR], 1.52; 95% CI, 1.03-2.25). For patients with seminomas, only primary tumor size was an independent risk factor for relapse (1.34, 1.02-1.75). CONCLUSION: In nonseminomatous germ cell tumors, craniocaudal nodal length was shown to be associated with increased risk of relapse independently of other known risk factors. If validated in an independent cohort, craniocaudal nodal length could provide important additional information to inform management decisions in these patients.

MRI-guided focused ultrasound surgery for uterine fibroid treatment: a cost-effectiveness analysis.

OBJECTIVE. The purpose of this article is to evaluate the cost effectiveness of a treatment strategy for symptomatic uterine fibroids that uses MRI-guided focused ultrasound as a first-line therapy relative to uterine artery embolization (UAE) or hysterectomy. MATERIALS AND METHODS. We developed a decision-analytic model to compare the cost effectiveness of three first-line treatment strategies: MRI-guided focused ultrasound, UAE, and hysterectomy. Treatment-specific short- and long-term utilities, lifetime costs, and quality-adjusted life years (QALYs) were incorporated, allowing us to conduct an incremental cost-effectiveness analysis, using a societal willingness-to-pay (WTP) threshold of $50,000/QALY to designate a strategy as cost effective. Sensitivity analyses were subsequently performed on all key parameters. RESULTS. In the base-case analysis, UAE as a first-line treatment of symptomatic fibroids was the most effective and expensive strategy (22.75 QALYs; $22,968), followed by MRI-guided focused ultrasound (22.73 QALYs; $20,252) and hysterectomy (22.54 QALYs; $11,253). MRI-guided focused ultrasound was cost effective relative to hysterectomy, with an associated incremental cost-effectiveness ratio (ICER) of $47,891/QALY. The ICER of UAE relative to MRI-guided focused ultrasound was $234,565/QALY, exceeding the WTP threshold of $50,000/QALY, therefore rendering MRI-guided focused ultrasound also cost effective relative to UAE. In sensitivity analyses, results were robust to changes in most parameters but were sensitive to changes in probabilities of recurrence, symptom relief, and quality-of-life measures. CONCLUSION. First-line treatment of eligible women with MRI-guided focused ultra-sound is a cost-effective noninvasive strategy. For those not eligible for MRI-guided focused ultra-sound, UAE remains a cost-effective option. These recommendations integrate both the short- and long-term decrements in quality of life associated with the specific treatment modalities.

A case study of a pilot leadership skills program to clarify professional fulfillment sources for academic physicians.

PURPOSE: In this case study, the authors aimed to investigate the usefulness of five interactive workshops on leadership skills relevant to academic physicians for their professional fulfillment. Workshops were led by experts in finance, negotiation, business administration and digital tools and enhanced a practical understanding of skills in 1) financial investment; 2) growing clout on social media; 3) negotiation; 4) navigating institutional culture as a woman; and 5) conflict management. DESIGN/METHODOLOGY/APPROACH: Workshops were deployed to faculty in the departments of Radiology and Psychiatry. Attendance at seminars was captured, categorized as in-person (when offered), virtual-live or virtual-recording views post hoc. The authors also collected responses to a brief, 5-question survey which assessed faculty familiarity with the topic pre-and post-seminar and evaluated the perceived relevance of the topic to professional fulfillment. FINDINGS: The highest attendance was for the seminar on financial investments, and the lowest attendance was for that on conflict management. The seminar that the highest proportion of respondents deemed important as a leadership skill was on the topic of navigating institutional culture as a woman in the workplace. The seminar that focused on cultivating clout on social media was the seminar that the highest proportion of respondents deemed worth attending. ORIGINALITY/VALUE: From this case study, the authors learned that financial literacy, discerning institutional culture, managing conflicts, negotiating and using digital tools are topics which have relevance to physician professional fulfillment. Such topics could be valuable as the building blocks for future programs which provide leadership training to physicians.

A Phase II Prospective Blinded Trial of Magnetic Resonance Imaging and In-Bore Biopsy in Active Surveillance for Prostate Cancer.

OBJECTIVE: To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance. METHODS: This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI. RESULTS: We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies). CONCLUSION: The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other.

Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer.

Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. J. Magn. Reson. Imaging 2013;37:1035-1054. © 2013 Wiley Periodicals, Inc.

Quantitative diffusion MRI in prostate cancer: Image quality, what we can measure and how it improves clinical assessment.

Diffusion-weighted imaging is a dependable method for detection of clinically significant prostate cancer. In prostate tissue, there are several compartments that can be distinguished from each other, based on different water diffusion decay signals observed. Alterations in cell architecture, such as a relative increase in tumor infiltration and decrease in stroma, will influence the observed diffusion signal in a voxel due to impeded random motion of water molecules. The amount of restricted diffusion can be assessed quantitatively by measuring the apparent diffusion coefficient (ADC) value. This is traditionally calculated using a monoexponential decay formula represented by the slope of a line produced between the logarithm of signal intensity decay plotted against selected b-values. However, the choice and number of b-values and their distribution, has a significant effect on the measured ADC values. There have been many models that attempt to use higher-order functions to better describe the observed diffusion signal decay, requiring an increased number and range of b-values. While ADC can probe heterogeneity on a macroscopic level, there is a need to optimize advanced diffusion techniques to better interrogate prostate tissue microstructure. This could be of benefit in clinical challenges such as identifying sparse tumors in normal prostate tissue or better defining tumor margins. This paper reviews the principles of diffusion MRI and novel higher order diffusion signal analysis techniques to improve the detection of prostate cancer.