Local Staging Of Prostate Cancer Research Articles

Biparametric MRI for Local Staging of Prostate Cancer: Current Status and Future Applications.

Multiparametric magnetic resonance imaging (mpMRI) is the recommended modality for local staging of prostate cancer (PCa). The use of dynamic contrast-enhanced (DCE) imaging alone significantly improves staging performance. However, several studies have revealed that DCE imaging adds no extra benefit for PCa detection. Many authors observed benefits of performing prostate MRI without DCE, so called biparametric MRI (bpMRI), such as the elimination of the toxicity of gadolinium administration, reduction of examination time, costs and better accessibility. This narrative review describes the variety of imaging modalities in Local staging of PCa with bpMRI utilization and its comparison to mpMRI. A search of medical databases was performed to find eligible articles using the following key words: "prostate cancer", "MRI", "multiparametric", "biparametric" and "staging". MEDLINE, Web of Science, PubMed and Google Scholar were used to search for eligible articles published in the past 5 years and compared the diagnostic accuracy of mpMRI and bp MRI in local staging of PCa. A total of 48 articles were evaluated. Multiple systematic reviews used pooled data to compare the accuracy of biparametric and multiparametric examinations. However, all these studies advise caution on using pooled data for clinical practice, pointing to multiple sources of heterogeneity among the studies evaluated. Given the absence of prospective data comparing bpMRI and mpMRI, randomized, prospective, multicenter studies are encouraged. However, mpMRI is the recommended modality for local staging of PCa. It has superior performance compared to traditional staging based on clinical nomograms, and provides additional information on the site and extent of disease.

Comparisons of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in diagnosing prostate cancer based on tumor detection, localization and staging.

To evaluate the diagnostic ability of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in detecting and localizing lesions, and further clarify the accuracy of these examinations in tumor staging. Seventy patients who underwent mpMRI, 68Ga-PSMA PET/CT and radical prostatectomy were enrolled. The abilities to detect index and clinically significant lesions by three examinations were compared. We further evaluated the ability of these examinations to localize lesions to the superior, inferior, anterior, posterior, left and right halves of the prostate and analyzed their accuracy in local and lymph node staging. There were no significant differences among mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in their ability to detect index (p = 0.48, p = 0.23 and p = 0.07) and clinically significant lesions (p = 0.30, p = 0.29 and p = 0.06) or to localize lesions in six half divisions of the prostate. With postoperative pathology as reference, both mpMRI (p = 0.10) and mpMRI combined with 68Ga-PSMA PET/CT (p = 0.10) can accurately assess the local staging of prostate cancer. However, 68Ga-PSMA PET/CT underestimates the local staging of prostate cancer (p < 0.01). Regarding lymph node staging, the three types of examination showed no significant differences compared to postoperative pathology (p = 0.63, p = 0.51 and p = 0.14). With postoperative pathology as reference, 68Ga-PSMA PET/CT underestimates the local tumor staging. MpMRI combined with 68Ga-PSMA PET/CT has no obvious advantages in detecting, localizing or staging prostate cancer compared with mpMRI.

The Role of Multiparametric MRI in the Local Staging of Prostate Cancer.

Prostate cancer ranks as the second most frequently diagnosed cancer globally among men and stands as the fifth leading cause of cancer-related death in males. Hence, an early and precise diagnosis and staging are critical. Traditional staging is based on clinical nomograms but presents a lower performance than prostate multiparametric magnetic resonance imaging (mpMRI). Since tumor staging serves as the basis for risk stratification, prognosis, and treatment decision-making, the primary objective of mpMRI is to distinguish between organ-confined and locally advanced diseases. Therefore, this imaging modality has emerged as the optimal selection for the local staging of prostate cancer, offering incremental value in evaluating pelvic nodal disease and bone involvement, and supplying supplementary insights regarding the precise location and disease extension. As per the Prostate Imaging Reporting & Data System v2.1 guideline, a comprehensive and accurate mpMRI requires several key sequences, which include T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) for morphological assessment, with T2WI serving as the cornerstone for local staging. Additionally, diffusion-weighted imaging (DWI) and dynamic sequences acquired with intravenous administration of paramagnetic contrast medium (DCE) are crucial components. It is worth noting that while MRI exhibits high specificity, its sensitivity in diagnosing extracapsular extension, seminal vesicle invasion, and lymph node metastases is limited. Moreover, mpMRI has its own constraints and is not as effective in detecting distant metastases or evaluating lymph nodes, for which extended pelvic lymph node dissection remains the gold standard. This review aims to highlight the significance of mpMRI in prostate cancer staging and provide a practical approach to assessing extracapsular extension, seminal vesicle invasions, and the involvement of adjacent organs and lymph nodes.

Local Staging of Prostate Cancer at MRI: What the Urologist and Radiation Oncologist Want to Know.

Local Staging of Prostate Cancer at MRI: What the Urologist and Radiation Oncologist Want to Know.

Staging of Prostate Cancer: Role of Multiparametric Magnetic Resonance Imaging in Different Risk Classes.

Using multiparametric magnetic resonance imaging, it is now possible to diagnose prostate cancer and categorize its risk. As it can accurately determine the extracapsu- lar extension of the tumor, invasion of seminal vesicles, involvement of lymph nodes, and the potential presence of bone metastases, multiparametric magnetic resonance imaging plays a crucial role not only in the diagnosis but also in the local staging of prostate cancer. The patients with a history of negative biopsy/increasing prostate- specific antigen and the existence of further data supporting its use in biopsy-naive patients and active surveillance are the most blatant indications for multiparametric magnetic resonance imaging in guidelines. The traditional clinical examination, pros- tate-specific antigen tests, and systematic biopsy are all enhanced by multiparametric magnetic resonance imaging, which will miss certain cancers due to insufficient size or changes in tissue density. The use of multiparametric magnetic resonance imaging is expected to rise, and further advances in the method will be crucial for the secure adoption of targeted therapeutic ideas. Here, we give a succinct overview of multipa- rametric magnetic resonance imaging's application to the identification and risk clas- sification of prostate cancer.

MR image quality in local staging of prostate cancer: Role of PI-QUAL in the detection of extraprostatic extension

PurposeTo assess the impact of prostate MRI image quality by means of the Prostate Imaging Quality (PI-QUAL) score, on the identification of extraprostatic extension of disease (EPE), predicted using the EPE Grade Score, Likert Scale Score (LSS) and a clinical nomogram (MSKCCn). MethodsWe retrospectively included 105 patients with multiparametric prostate MRI prior to prostatectomy. Two radiologists evaluated image quality using PI-QUAL (≥4 was considered high quality) in consensus. All cases were also scored using the EPE Grade, the LSS, and the MSKCCn (dichotomized). Inter-rater reproducibility for each score was also assessed. Accuracy was calculated for the entire population and by image quality, considering two thresholds for EPE Grade (≥2 and = 3) and LSS (≥3 and ≥ 4) and using McNemar’s test for comparison. ResultsOverall, 66 scans achieved high quality. The accuracy of EPE Grade ranged from 0.695 to 0.743, while LSS achieved values between 0.705 and 0.733. Overall sensitivity for the radiological scores (range = 0.235–0.529) was low irrespective of the PI-QUAL score, while specificity was higher (0.775–0.986). The MSKCCn achieved an AUC of 0.76, outperforming EPE Grade (=3 threshold) in studies with suboptimal image quality (0.821 vs 0.564, p = 0.016). EPE Grade (=3 threshold) accuracy was also better in high image quality studies (0.849 vs 0.564, p = 0.001). Reproducibility was good to excellent overall (95 % Confidence Interval range = 0.782–0.924). ConclusionAssessing image quality by means of PI-QUAL is helpful in the evaluation of EPE, as a scan of low quality makes its performance drop compared to clinical staging tools.

Quality assessment of prostate MRI by PI-QUAL score: Inter-reader agreement and impact on prostate cancer local staging at 3 Tesla

PurposeTo evaluate whether the Prostate Imaging Quality (PI-QUAL) score impacts prostate cancer (PCa) staging on MRI. The secondary goal was to test inter-reader agreement among radiologists experienced in prostate imaging. MethodA retrospective, single-center study with patients who underwent 3 Tesla prostate MRI scans and were submitted to radical prostatectomy (RP) between January 2018 and November 2021 and were eligible for our study. Extraprostatic extension (EPE) data were collected from original MR reports (EPEm) and pathological reports of RP specimens (EPEp). Three expert prostate radiologists (ESUR/ESUI criteria R1, R2, R3) independently evaluated all MRI exams according to PI-QUAL score for image quality (1 to 5; 1: poor, 5: excellent), blinded to original imaging reports and clinical data. We studied the diagnostic performance of MRI using pooled data from PI-QUAL scores (≤3 vs. ≥4). We also performed univariate and multivariate analyses to assess the PI-QUAL score impact on local PCa staging. Cohen’s K and Tau-b Kendall tests were used to assess the inter-reader agreement for PI-QUAL score, T2WI, DWI, and DCE. ResultsOur final cohort included 146 patients, of which 27.4% presented EPE on pathology. We observed no impact of imaging quality on accuracy for EPE prediction: AUC of 0.750 (95% CI 0.26-1) for PI-QUAL ≤ 3 and 0.705 (95% CI 0.618–0.793) for PI-QUAL ≥ 4. The multivariate analysis demonstrated a correlation of EPEm (OR 3.25, p 0.001) and ISUP grade group (OR 1.89, p 0.012) to predict EPEp. The inter-reader agreement was moderate to substantial (0.539 for R1-R2, 0.522 for R2-R3, and 0.694 for R1-R3). ConclusionOur clinical impact evaluation showed no direct correlation between MRI quality by PI-QUAL score and accuracy in detecting EPE in patients undergoing RP. Additionally, we had moderate to a substantial inter-reader agreement for the PI-QUAL score.

Quantitative MRI in the Local Staging of Prostate Cancer: A Systematic Review and Meta-Analysis.

Local staging of prostate cancer (PCa) is important for treatment planning. Radiologist interpretation using qualitative criteria is variable with high specificity but low sensitivity. Quantitative methods may be useful in the diagnosis of extracapsular extension (ECE). To assess the performance of quantitative MRI markers for detecting ECE. Systematic review and meta-analysis. 4800 patients from 28 studies with histopathologically confirmed PCa on radical prostatectomy were pooled for meta-analysis. Patients from 46 studies were included for systematic review. Diffusion-weighted, T2-weighted, and dynamic contrast-enhanced MRI at 1.5 T or 3 T. PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched to identify studies on diagnostic test accuracy or association of any quantitative MRI markers with ECE. Results extracted by two independent reviewers for tumor contact length (TCL) and mean apparent diffusion coefficient (ADC-mean) were pooled for meta-analysis, but not for other quantitative markers including radiomics due to low number of studies available. Hierarchical summary receiver operating characteristic (HSROC) curves were computed for both TCL and ADC-mean, but summary operating points were computed for TCL only. Heterogeneity was investigated by meta-regression. Results were significant if P ≤ 0.05. At the 10 mm threshold for TCL, summary sensitivity and specificity were 0.76 [95% confidence interval (CI) 0.71-0.81] and 0.68 [95% CI 0.63-0.73], respectively. At the 15 mm threshold, summary sensitivity and specificity were 0.70 [95% CI 0.53-0.83] and 0.74 [95% CI 0.60-0.84] respectively. The area under the HSROC curves for TCL and ADC-mean were 0.79 and 0.78, respectively. Significant sources of heterogeneity for TCL included timing of MRI relative to biopsy. Both 10 mm and 15 mm thresholds for TCL may be reasonable for clinical use. From comparison of the HSROC curves, ADC-mean may be superior to TCL at higher sensitivities. 3 TECHNICAL EFFICACY STAGE: 2.

Inherited risk for prostate cancer (PCa): Following the natural history of men with high-risk genetics using multiparametric MRI (mpMRI).

390 Background: PCa has inherited risk factors including high genetic risk variants such as BRCA1/2, HOXB13, and DNA mismatch repair genes. mpMRI has been shown to be effective for detection and staging of localized PCa. This study follows participants (prts), born biologically male, without a diagnosis of PCa with known germline pathogenic or likely pathogenic variants (PV) in BRCA1/2, MLH1, MSH2, MSH6, PMS2, EPCAM, HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C/D, BRIP1, or FANCA-FANCM (NCT03805919). Methods: Up to 500 eligible prts 30-75 years old (yo) with a documented germline PV will enroll. Prts undergo biennial clinical exam and mpMRI, and annual PSA monitoring and are followed at 12-month intervals to determine PSA, prostate cancer diagnosis, and/or disease/survival status until death. Indication for prostate biopsy includes clinical or imaging findings. Biopsy specimens undergo molecular analyses. Results: To date, 175 prts have been enrolled: 169 (97%) White, 3 Hispanic (2%), 1 African American (1%), 1 Asian (1%), and 1 biethnic (1%). Median age is 47 yo. The most common monoallelic PV are: 48.6% BRCA2, 25.1% BRCA1, 6.3% CHEK2 and 5.7% MSH2. PVs in ATM, PALB2, HOXB13, PMS2, MLH1, MSH6, BRIP1, EPCAM and RAD51D are ≤4%. One subject carries three distinct PVs ( BRCA2, CHEK2, BRIP1). Indication for biopsy was found in 26.3% of prts with 22/46 (47.8%) with a PIRADS 4 lesion, 6/46 (13.0%) PIRADS 3 lesion, 12/46 (26.1%) elevated PSA (median=2.8 ng/mL) or 6/46 (13.0%) due to clinical discretion. Adenocarcinoma was diagnosed on 13/39 (33.3%) biopsies with median age at diagnosis=59 yo. 9/13 (69%) prts had a PSA &lt;3 ng/ml at diagnosis. Nine prts were diagnosed with ISUP Grade Group (GG) 1, 3 with GG2, and 1 with GG3. Eight prts opted for active surveillance (AS), 2 for radiation therapy (RT), and 3 for prostatectomy (RP). Two prts on AS converted to definitive treatment (one RP and one RT) due to progression in GG on the year 1 AS biopsy. Conclusions: mpMRI screening in men with germline PV can be used for diagnosis and monitoring of PCa and facilitates detection below conventional PSA thresholds in a high genetic risk setting. Access to genetic testing and other variables need to be addressed in underrepresented minorities. Correlative studies, including cfDNA and PBMCs, are ongoing. Clinical trial information: NCT03805919 . [Table: see text]

Could Biparametric MRI Replace Multiparametric MRI in the Management of Prostate Cancer?

Prostate cancer (PCa) is a worldwide epidemiological problem, since it is one of the most prevalent types of neoplasia among men, and the third-leading cause of cancer-related deaths, after lung and colorectal tumors. Unfortunately, the early stages of PCa have a wide range of unspecific symptoms. For these reasons, early diagnosis and accurate evaluation of suspicious lesions are crucial. Multiparametric MRI (mpMRI) is currently the imaging modality of choice for diagnostic screening and local staging of PCa, but also has a leading role in guiding biopsies and in treatment biparametric MRI (bpMRI) could partially replace mpMRI due to its lack of adverse reactions caused by contrast agents, relatively lower costs, and shorter acquisition time. Further, 31 relevant articles regarding the advantages and disadvantages of the aforementioned imaging techniques were scanned. As a result, while bpMRI has comparable accuracy in detecting PCa, its roles in the other steps of PCa management are limited.

The impact of local staging of prostate cancer determined on MRI or DRE at time of radical prostatectomy on progression-free survival: A Will Rogers phenomenon

IntroductionWe aimed to test whether the current practice of using mpMRI stage might lead to a Will Rogers phenomenon with a stage migration compared to DRE in men undergoing radical prostatectomy. Material and methodsA total of 572 consecutive patients who underwent radical prostatectomy at a single institution (2007–2017) were included. Clinical stage using digital rectal examination was determined on table by the operating surgeon; mpMRI and pathological stage were recorded after tumor board review. Progression-free survival (PFS) was defined as no rising PSA, no adjuvant/salvage treatment, and no metastases or mortality. PFS was compared between groups and a model incorporating mpMRI into the EAU risk groups was created. ResultsMedian age was 63 years (IQR 58.5–67) and median PSA was 8.9 ng/ml (IQR 6.5–13.2). Using DRE stage, 20% were NCCN low risk, 43% were intermediate, and 37% high. Median follow-up was 48 months (IQR 22–73). Estimated PFS at 1, 3, and 5 years was 75%, 59%, and 54%, respectively. When comparing PFS between DRE and mpMRI stages, patients deemed T1 (P < 0.01) or T3 (P = 0.03) by mpMRI showed better outcomes than patients staged T1 or T3 by DRE. On univariable analysis lower risk for failure was seen for MRI T1 disease (HR 0.10 95%, CI 0.01–0.73, P = 0.02) or MRI T3 (HR 0.70, CI 0.51–0.97, P = 0.03). On multivariable analysis, only MRI T1 remained a significant predictor (HR 0.08, 95% CI 0.01–0.59, P = 0.01). The subsequent, modified EAU risk model using both DRE and mpMRI performed significantly better than the DRE model. ConclusionPFS based on mpMRI is not the same as DRE staging. Current risk groups which use DRE should be used with caution in whom local stage is based on mpMRI. Our modified EAU-risk categories can provide greater accuracy.

Abstract 999: Epigenetic loss of heterogeneity from low to high grade localized prostate tumors

Abstract Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequenced the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumors. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumors. Despite this loss, high-grade tumors exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory program. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumors. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumors, critical for molecular stratification of the disease. Citation Format: Ece Sebnem Eksi, Zeynep Sayar, Alex Chitsazan, George T. Thomas, Andrew Adey, Paul T. Spellman, Ryan Kopp. Epigenetic loss of heterogeneity from low to high grade localized prostate tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 999.

Quantitative imaging parameters to predict the local staging of prostate cancer in intermediate- to high-risk patients

ObjectivesPSMA PET/MRI showed the potential to increase the sensitivity for extraprostatic disease (EPD) assessment over mpMRI; however, the interreader variability for EPD is still high. Therefore, we aimed to assess whether quantitative PSMA and mpMRI imaging parameters could yield a more robust EPD prediction.MethodsWe retrospectively evaluated PCa patients who underwent staging mpMRI and [68Ga]PSMA-PET, followed by radical prostatectomy at our institution between 01.02.2016 and 31.07.2019. Fifty-eight cases with PET/MRI and 15 cases with PET/CT were identified. EPD was determined on histopathology and correlated with quantitative PSMA and mpMRI parameters assessed by two readers: ADC (mm2/1000 s), longest capsular contact (LCC, mm), tumor volume (cm3), PSMA-SUVmax and volume-based parameters using a fixed threshold at SUV > 4 to delineate PSMAtotal (g/ml) and PSMAvol (cm3). The t test was used to compare means, Pearson’s test for categorical correlation, and ROC curve to determine the best cutoff. Interclass correlation (ICC) was performed for interreader agreement (95% CI).ResultsSeventy-three patients were included (64.5 ± 6.0 years; PSA 14.4 ± 17.1 ng/ml), and 31 had EPD (42.5%). From mpMRI, only LCC reached significance (p = 0.005), while both volume-based PET parameters PSMAtotal and PSMAvol were significantly associated with EPD (p = 0.008 and p = 0.004, respectively). On ROC analysis, LCC, PSMAtotal, and PSMAvol reached an AUC of 0.712 (p = 0.002), 0.709 (p = 0.002), and 0.718 (p = 0.002), respectively. ICC was moderate–good for LCC 0.727 (0.565–0.828) and excellent for PSMAtotal and PSMAvol with 0.944 (0.990–0.996) and 0.985 (0.976–0.991), respectively.ConclusionsQuantitative PSMA parameters have a similar potential as mpMRI LCC to predict EPD of PCa, with a significantly higher interreader agreement.

Integration of Prostate Biopsy Results with Pre-Biopsy Multiparametric Magnetic Resonance Imaging Findings Improves Local Staging of Prostate Cancer.

To assess the added value of histological information for local staging of prostate cancer (PCa) by comparing the accuracy of multiparametric MRI alone (mpMRI) and mpMRI with biopsy Gleason grade (mpMRI+Bx). 133 consecutive patients who underwent preoperative 3T-MRI and subsequent radical prostatectomy for PCa were included in this single-centre retrospective study. mpMRI imaging was reviewed independently by two uroradiologists for the presence of extracapsular extension (ECE) and seminal vesicle invasion (SVI) on a 5-point Likert scale. For second reads, the radiologists received results of targeted fused MR/US biopsy (mpMRI+Bx) prior to re-staging. The median patient age was 63years (interquartile range (IQR) 58-67years) and median PSA was 6.5ng/mL (IQR 5.0-10.0ng/mL). Extracapsular extension was present in 85/133 (63.9%) patients and SVI was present in 22/133 (16.5%) patients. For ECE prediction, mpMRI showed sensitivity and specificity of 63.5% and 81.3%, respectively, compared to 77.7% and 81.3% achieved by mpMRI+Bx. At an optimal cut-off value of Likert score ≥ 3, areas under the curves (AUCs) was .85 for mpMRI+Bx and .78 for mpMRI, P < .01. For SVI prediction, AUC was .95 for mpMRI+Bx compared to .92 for mpMRI; P = .20. Inter-reader agreement for ECE and SVI prediction was substantial for mpMRI (k range, .78-.79) and mpMRI+Bx (k range, .74-.79). MpMRI+Bx showed superior diagnostic performance with an increased sensitivity for ECE prediction but no significant difference for SVI prediction. Inter-reader agreement was substantial for both protocols. Integration of biopsy information adds value when staging prostate mpMRI.

Local Extent of Prostate Cancer at MRI versus Prostatectomy Histopathology: Associations with Long-term Oncologic Outcomes.

Background It is unknown how the imperfect accuracy of MRI for local staging of prostate cancer relates to oncologic outcomes. Purpose To analyze how staging discordances between MRI and histopathologic evaluation relate to recurrence and survival after radical prostatectomy. Materials and Methods Health Insurance Portability and Accountability Act-compliant retrospective analysis of preprostatectomy T2-weighted prostate MRI (January 2001 to December 2006). Extraprostatic extension and seminal vesicle invasion were assessed by using five-point Likert scales; scores of 4 or higher were classified as positive. Biochemical recurrence (BCR), metastases, and prostate cancer-specific mortality rates were estimated with Kaplan-Meier and Cox models. Results A total of 2160 patients (median age, 60 years; interquartile range, 55-64 years) were evaluated. Among patients with histopathologic extraprostatic (pT3) disease (683 of 2160; 32%), those with organ-confined disease at MRI (384 of 683; 56%) experienced better outcomes than those with concordant extraprostatic disease at MRI and pathologic analysis: 15-year risk for BCR, 30% (95% CI: 22, 40) versus 68% (95% CI: 60, 75); risk for metastases, 14% (95% CI: 8.4, 24) versus 32% (95% CI: 26, 39); risk for prostate cancer-specific mortality, 3% (95% CI: 1, 6) versus 15% (95% CI: 9.5, 23) (P < .001 for all comparisons). Among patients with histopathologic organ-confined disease (pT2) (1477 of 2160; 68%), those with extraprostatic disease at MRI (102 of 1477; 7%) were at higher risk for BCR (27% [95% CI: 19, 37] vs 10% [95% CI: 8, 14]; P < .001), metastases (19% [95% CI: 6, 48] vs 3% [95% CI: 1, 6]; P < .001), and prostate cancer-specific mortality (2% [95% CI: 1, 9] vs 1% [95% CI: 0, 5]; P = .009) than those with concordant organ-confined disease at MRI and pathologic analysis. At multivariable analyses, tumor extent at MRI (hazard ratio range, 4.1-5.2) and histopathologic evaluation (hazard ratio range, 3.6-6.7) was associated with the risk for BCR, metastases, and prostate cancer-specific mortality (P < .001 for all analyses). Conclusion The local extent of prostate cancer at MRI is associated with oncologic outcomes after prostatectomy, independent of pathologic tumor stage. This might inform a strategy on how to integrate MRI into a clinical staging algorithm. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gottlieb in this issue.

Epigenetic loss of heterogeneity from low to high grade localized prostate tumours

Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumours. Despite this loss, high-grade tumours exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory programme. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumours. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumours, critical for molecular stratification of the disease.

Local Staging of Prostate Cancer with Multiparametric MRI

Abstract Multiparametric magnetic resonance imaging (mpMRI) plays several valuable roles in preoperative staging of adenocarcinoma of the prostate gland, including detection of clinically significant disease, determination of extraglandular extension, and assessment of nodal disease. The Prostate Imaging Reporting and Data System (PI-RADS) establishes certain acceptable technical standards for mpMRI. These technical parameters allow for consistent image quality, enabling accurate detection and staging of disease; this in turn has significant implications for treatment recommendations. The prostate gland has a characteristic zonal anatomy, with cancers arising from the peripheral zone tending to demonstrate more aggressive histologic features. The acquisition of several sequences as part of mpMRI protocol allows for assessment of locoregional disease as well as regional and distant lymphadenopathy. The local staging of prostate cancer with mpMRI is reviewed in this article.

MRI utility in predicting extraprostatic extension of prostate cancer and biochemical recurrence after radical prostatectomy

Introduction. The study aimed to evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and the Martini model to predict extraprostatic extension (EPE) and biochemical recurrence (BCR) of prostate cancer (PCa). Materials and methods. 61 patients underwent a radical laparoscopic prostatectomy. The preoperative risk of EPE was determined using mpMRI and the Martini model. Results. MpMRI predicts the presence of EPE of PCa with a sensitivity and specificity of 47.4% and 85.7%, respectively (AUC 0.66, 95% CI: 0.51–0.82, p = 0.046). The Martini model’s sensitivity was higher, but the specificity was lower than that of mpMRI and was 84.2% and 66.7%, respectively (AUC 0.78, 95% CI: 0.66–0.89, p &lt; 0.001). Univariate and multivariate Cox analysis indicated that EPE in mpMRI (HR 6.6, 95% CI: 1.8–24.1), and the presence of positive surgical margins (PSM) (HR 7.1, 95% CI: 1.9–26.7) are independent factors increasing the probability of BCR. Conclusions. MpMRI and Martini model are valuable tools in local staging of PCa, managing and predicting the oncological treatment outcomes of patients with PCa.

Out-of-bounds: The significance of extraprostatic extension on multiparametric magnetic resonance imaging for local staging of prostate cancer.

Out-of-bounds: The significance of extraprostatic extension on multiparametric magnetic resonance imaging for local staging of prostate cancer.

MRI/PET Imaging in elevated PSA and localized prostate cancer: a narrative review.

ObjectiveTo review the recent milestones in MRI and PET based imaging and evaluate their evolving role in the setting of elevated PSA as well as localized prostate cancer.BackgroundThe importance of multiparametric MRI (mpMRI) and PET based imaging for the diagnosis and staging of prostate cancer cannot be understated. Accurate staging has become another significant milestone with the use of PET scans, particularly with prostate specific radiotracers like 68-Gallium Prostate Specific Membrane Antigen (68Ga-PSMA). Integrated PET/MRI systems are commercially available and can be modulated to evaluate the unique needs of localized as well as recurrent prostate cancer.MethodsA literature search was performed using PubMed and Google Scholar using the MeSH compliant and other keywords that included prostate cancer, PSA, mpMRI, PET CT, PET/MRI.ConclusionsmpMRI has now established itself as the gold-standard of local prostate imaging and has been incorporated into international guidelines as part of the diagnostic work-up of prostate cancer. PSMA PET/CT has shown superiority over conventional imaging even in staging of localized prostate cancer based on recent randomized control data. Imaging parameters from PET/MRI have been shown to be associated with malignancy, Gleason score and tumour volume. As mpMRI and PSMA PET/CT become more ubiquitous and established; we can anticipate more high-quality data, cost optimization and increasing availability of PET/MRI to be ready for primetime in localized prostate cancer.