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1.
Cell ; 187(10): 2502-2520.e17, 2024 May 09.
Article En | MEDLINE | ID: mdl-38729110

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.


Imaging, Three-Dimensional , Prostatic Neoplasms , Humans , Imaging, Three-Dimensional/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Male , Prognosis , Deep Learning , X-Ray Microtomography/methods , Supervised Machine Learning
2.
World J Urol ; 42(1): 322, 2024 May 15.
Article En | MEDLINE | ID: mdl-38747982

PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.


Prostate-Specific Antigen , Prostate , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostate-Specific Antigen/blood , Aged , Middle Aged , Organ Size , Prostate/pathology , Prostate/diagnostic imaging , Risk Assessment , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Clinical Decision-Making , Multiparametric Magnetic Resonance Imaging , Prospective Studies
3.
Sci Rep ; 14(1): 11083, 2024 05 15.
Article En | MEDLINE | ID: mdl-38745087

The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa.


Contrast Media , Nomograms , Prostatic Neoplasms , Ultrasonography , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Ultrasonography/methods , Aged , Middle Aged , Prostate-Specific Antigen/blood , Prostate/diagnostic imaging , Prostate/pathology , Aged, 80 and over
4.
Radiology ; 311(2): e230750, 2024 May.
Article En | MEDLINE | ID: mdl-38713024

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.


Deep Learning , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Prospective Studies , Multiparametric Magnetic Resonance Imaging/methods , Middle Aged , Algorithms , Prostate/diagnostic imaging , Prostate/pathology , Image-Guided Biopsy/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods
5.
Sci Rep ; 14(1): 10908, 2024 05 13.
Article En | MEDLINE | ID: mdl-38740809

The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy: ISUP < 4 and PSA doubling time (PSAdt) > 12 months for low risk, and ISUP ≥ 4 or PSAdt ≤ 12 months for high risk. This dual-center retrospective study aims to investigate the correlation between the EAU risk stratification for BCR following radical prostatectomy and the detection rate of lesions using 18F-PSMA-1007 PET/CT. Among the 71 included patients (58 high-risk, 13 low-risk), with a median PSA level of 1.43 ng/ml, PET/CT demonstrated a significantly higher positivity in the high-risk group compared to the low-risk group (72.4% vs. 38.0%, p = 0.026). Analysis of recurrence sites revealed a similar proportion of pelvic-confined disease in both groups (24.1% vs. 23.1%, p = 0.935), but a significantly higher incidence of metastatic disease in the high-risk group (51.7% vs. 15.4%, p = 0.017), with detailed findings indicating an increased prevalence of bone metastases in the high-risk BCR group (37.8% vs. 7.7%, p = 0.048). Therefore, PSMA PET/CT offers valuable insights for treatment decisions, aligning with the evolving landscape of prostate cancer management.


Neoplasm Recurrence, Local , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Retrospective Studies , Aged , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Prostatectomy , Prostate-Specific Antigen/blood , Oligopeptides/chemistry , Niacinamide/analogs & derivatives
6.
Oncotarget ; 15: 288-300, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712741

PURPOSE: Sequential PET/CT studies oncology patients can undergo during their treatment follow-up course is limited by radiation dosage. We propose an artificial intelligence (AI) tool to produce attenuation-corrected PET (AC-PET) images from non-attenuation-corrected PET (NAC-PET) images to reduce need for low-dose CT scans. METHODS: A deep learning algorithm based on 2D Pix-2-Pix generative adversarial network (GAN) architecture was developed from paired AC-PET and NAC-PET images. 18F-DCFPyL PSMA PET-CT studies from 302 prostate cancer patients, split into training, validation, and testing cohorts (n = 183, 60, 59, respectively). Models were trained with two normalization strategies: Standard Uptake Value (SUV)-based and SUV-Nyul-based. Scan-level performance was evaluated by normalized mean square error (NMSE), mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Lesion-level analysis was performed in regions-of-interest prospectively from nuclear medicine physicians. SUV metrics were evaluated using intraclass correlation coefficient (ICC), repeatability coefficient (RC), and linear mixed-effects modeling. RESULTS: Median NMSE, MAE, SSIM, and PSNR were 13.26%, 3.59%, 0.891, and 26.82, respectively, in the independent test cohort. ICC for SUVmax and SUVmean were 0.88 and 0.89, which indicated a high correlation between original and AI-generated quantitative imaging markers. Lesion location, density (Hounsfield units), and lesion uptake were all shown to impact relative error in generated SUV metrics (all p < 0.05). CONCLUSION: The Pix-2-Pix GAN model for generating AC-PET demonstrates SUV metrics that highly correlate with original images. AI-generated PET images show clinical potential for reducing the need for CT scans for attenuation correction while preserving quantitative markers and image quality.


Deep Learning , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Positron Emission Tomography Computed Tomography/methods , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Middle Aged , Glutamate Carboxypeptidase II/metabolism , Antigens, Surface/metabolism , Image Processing, Computer-Assisted/methods , Algorithms , Radiopharmaceuticals , Reproducibility of Results
7.
World J Urol ; 42(1): 297, 2024 May 06.
Article En | MEDLINE | ID: mdl-38709326

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.


Image-Guided Biopsy , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prospective Studies , Image-Guided Biopsy/methods , Aged , Middle Aged , Prostate/pathology , Prostate/diagnostic imaging , Single-Blind Method
8.
J Nanobiotechnology ; 22(1): 224, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702709

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.


Carbocyanines , Mitochondria , Neoplasm Recurrence, Local , Photothermal Therapy , Prostatic Neoplasms , Male , Prostatic Neoplasms/diagnostic imaging , Photothermal Therapy/methods , Humans , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Cell Line, Tumor , Carbocyanines/chemistry , Optical Imaging/methods , Mice , Surgery, Computer-Assisted/methods , Fluorescent Dyes/chemistry , Mice, Nude , Mice, Inbred BALB C , Infrared Rays , Indocyanine Green/chemistry , Indocyanine Green/therapeutic use , Indocyanine Green/pharmacology
9.
Radiat Oncol ; 19(1): 54, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702761

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.


Prostatic Neoplasms , Radiosurgery , Radiotherapy, Image-Guided , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Radiosurgery/methods , Radiotherapy, Image-Guided/methods , Urinary Bladder/radiation effects , Organs at Risk/radiation effects , Organ Sparing Treatments/methods , Magnetic Resonance Imaging/methods , Prospective Studies , Quality of Life , Radiotherapy Dosage , Aged , Radiotherapy Planning, Computer-Assisted/methods , Middle Aged
10.
World J Urol ; 42(1): 285, 2024 May 02.
Article En | MEDLINE | ID: mdl-38695883

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.


Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Aged , Middle Aged , Risk Assessment , Gallium Isotopes , Image-Guided Biopsy/methods , Retrospective Studies , Prostate/pathology , Prostate/diagnostic imaging , Gallium Radioisotopes , Predictive Value of Tests , Nomograms , Biopsy/methods
11.
Cancer Epidemiol Biomarkers Prev ; 33(5): 641-642, 2024 May 01.
Article En | MEDLINE | ID: mdl-38689575

The primary benefit of prostate MRI in the modern diagnostic pathway for prostate cancer is that many men with elevated serum PSA can safely avoid an immediate biopsy if the MRI is nonsuspicious. It is less clear, though, how these patients should be followed thereafter. Are they to be followed the same as the general population, or do they warrant more attention because of the risk of a cancer missed on MRI? In this issue, Pylväläinen and colleagues report on incidence of clinically significant prostate cancer (csPCa) and clinically insignificant PCa (ciPCa) among patients who were referred for prostate MRI for clinical suspicion of csPCa in Helsinki but had a nonsuspicious MRI (nMRI). Compared with the general population in Finland, patients who had nMRI were approximately 3.4 times more likely to be diagnosed with csPCa and 8.2 times more likely to be diagnosed with ciPCa. Balancing the competing risks of a missed csPCa versus overdiagnosis in patients after nMRI requires integration of MRI and other risk factors, especially age and PSA density. This integration may be facilitated by multivariable models and quantitative pathology and imaging. See related article by Pylväläinen et al., p. 749.


Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Finland/epidemiology , Prostate-Specific Antigen/blood
12.
JAMA ; 331(17): 1452-1459, 2024 05 07.
Article En | MEDLINE | ID: mdl-38581254

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.


Early Detection of Cancer , Kallikreins , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Middle Aged , Biopsy , Early Detection of Cancer/methods , Kallikreins/blood , Magnetic Resonance Imaging , Neoplasm Grading , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostate/diagnostic imaging , Prostate/pathology
13.
Prostate ; 84(9): 823-831, 2024 Jun.
Article En | MEDLINE | ID: mdl-38606933

BACKGROUND: There are limited preclinical orthotopic prostate cancer models due to the technical complexity of surgical engraftment and tracking the tumor growth in the mouse prostate gland. Orthotopic xenografts recapitulate the tumor microenvironment, tumor stromal interactions, and clinical behavior to a greater extent than xenografts grown at subcutaneous or intramuscular sites. METHODS: This study describes a novel micro-surgical technique for orthotopically implanting intact tumors pieces from cell line derived (transgenic adenocarcinoma mouse prostate [TRAMP]-C2) or patient derived (neuroendocrine prostate cancer [NEPC]) tumors in the mouse prostate gland and monitoring tumor growth using magnetic resonance (MR) imaging. RESULTS: The TRAMP-C2 tumors grew rapidly to a predetermined endpoint size of 10 mm within 3 weeks, whereas the NEPC tumors grew at a slower rate over 7 weeks. The tumors were readily detected by MR and confidently identified when they were approximately 2-3 mm in size. The tumors were less well-defined on CT. The TRAMP-C2 tumors were characterized by amorphous sheets of poorly differentiated cells similar to a high-grade prostatic adenocarcinoma and frequent macroscopic peritoneal and lymph node metastases. In contrast, the NEPC's displayed a neuroendocrine morphology with polygonal cells arranged in nests and solid sheets and high count. There was a local invasion of the bladder and other adjacent tissues but no identifiable metastases. The TRAMP-C2 tumors were more hypoxic than the NEPC tumors. CONCLUSIONS: This novel preclinical orthotopic prostate cancer mouse model is suitable for either syngeneic or patient derived tumors and will be effective in developing and advancing the current selection of treatments for patients with prostate cancer.


Adenocarcinoma , Disease Models, Animal , Prostatic Neoplasms , Animals , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/diagnostic imaging , Mice , Humans , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Cell Line, Tumor , Mice, Transgenic , Neoplasm Transplantation/methods , Magnetic Resonance Imaging , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/therapy
14.
Technol Cancer Res Treat ; 23: 15330338241246636, 2024.
Article En | MEDLINE | ID: mdl-38629205

OBJECTIVE: This study intends to examine the anticipatory power of clinical and radiological parameters in detecting clinically significant prostate cancer in patients demonstrating Prostate Imaging Reporting and Data System 3 lesions. METHODS: This was a retrospective study. The study included participation from 453 patients at the First Affiliated Hospital of Soochow University, sampled between September 2017 through August 2022. Each patient underwent a routine 12-core prostate biopsy followed by a 2 to 5 core fusion-targeted biopsy. We utilized both univariate and multivariate logistic regression analyses to identify the parameters that have a correlation with clinically significant prostate cancer. The predictive ability of these parameters was assessed using the receiver operating characteristic curve, leading to the creation of a nomogram. RESULTS: Clinically significant prostate cancer was detected in 68 out of 453 patients with Prostate Imaging Reporting and Data System 3 lesions (15.01%). Among Prostate Imaging Reporting and Data System 3a and 3b patients, 4.78% (3.09% of the total) and 33.75% (11.92% of the total), respectively, had clinically significant prostate cancer. Systematic biopsy improved prostate cancer and clinically significant prostate cancer detection rates by 7.72% and 3.09%, respectively, compared to targeted biopsy. Without systematic biopsy, there would be an undetected rate of 15% for prostate cancer and 8.13% for clinically significant prostate cancer in Prostate Imaging Reporting and Data System 3b patients. Several clinical parameters, including age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination, were statistically significant in the logistic regression analysis for clinically significant prostate cancer. The individual diagnostic accuracies of these parameters for clinically significant prostate cancer were 0.648, 0.645, 0.75, 0.763, and 0.7, respectively, but their combined accuracy improved to 0.866. A well-fit nomogram based on the identified risk factors was constructed (χ2 = 10.254, P = .248). CONCLUSION: The combination of age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination presented a higher diagnostic value for clinically significant prostate cancer than any single parameter in patients with Prostate Imaging Reporting and Data System 3 lesions. Systematic biopsy proved crucial for biopsy-naive patients with Prostate Imaging Reporting and Data System 3 lesions and should not be omitted.


Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostate-Specific Antigen , Magnetic Resonance Imaging/methods , Retrospective Studies , Image-Guided Biopsy/methods
15.
Urol Pract ; 11(3): 538-546, 2024 May.
Article En | MEDLINE | ID: mdl-38640417

INTRODUCTION: The use of active surveillance (AS) for prostate cancer is increasing, and racial disparities have been identified in its implementation. We investigated differences by race and ethnicity in the utilization and intensity of AS by race and ethnicity among older men with low- and favorable intermediate-risk prostate cancer, with particular focus on the integration of multiparametric MRI (mpMRI) into AS protocols. METHODS: Using the Surveillance, Epidemiology, and End Results and Medicare fee-for-service linked database, we identified a cohort of men diagnosed between 2010 and 2017 with low- or favorable intermediate-risk prostate cancer. The odds of receiving AS were compared by patient race and ethnicity using multivariable logistic regression models, while the rates of usage of PSA tests, biopsy, and mpMRI within 2 years of diagnosis among men on AS were assessed using multivariable Poisson regression models. RESULTS: Our cohort included 33,542 men. The proportion of men with low-risk disease who underwent AS increased from 29.5% in 2010 to 51.7% in 2017, while the proportion among men with favorable intermediate disease grew from 11.4% to 17.2%. Hispanic (odds ratio [OR] = 0.68, 95% CI 0.58-0.79) and non-Hispanic Black men (OR = 0.78, 95% CI 0.68-0.89) were less likely to receive AS than non-Hispanic White men for low-risk disease, while non-Hispanic Black men were more likely to receive AS for favorable intermediate disease (OR = 1.21, 95% CI 1.04-1.39). Non-Hispanic Black men receiving AS underwent prostate MRI at a lower rate compared to non-Hispanic White men, regardless of whether they had low-risk (incidence rate ratio = 0.77, 95% CI 0.61-0.97) or favorable intermediate-risk (incidence rate ratio = 0.61, 95% CI 0.44-0.83) disease, respectively. CONCLUSIONS: The overall adoption of AS for low-risk prostate cancer increased among Medicare fee-for-service beneficiaries. However, a significant disparity exists for non-Hispanic Black men, as they exhibit lower rates of AS utilization. Moreover, non-Hispanic Black men are less likely to have access to novel technologies, such as mpMRI, as part of their AS protocols.


Prostatic Neoplasms , Watchful Waiting , Male , Humans , Aged , United States/epidemiology , Black or African American , Medicare , Prostatic Neoplasms/diagnostic imaging , White
17.
World J Urol ; 42(1): 249, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38649544

PURPOSE: Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role. METHODS: A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available. RESULTS: There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of the prostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI. CONCLUSION: There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills.


Forecasting , Image-Guided Biopsy , Prostate , Prostatic Neoplasms , Urology , Male , Humans , Image-Guided Biopsy/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostate/pathology , Prostate/diagnostic imaging
18.
BMC Urol ; 24(1): 92, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643097

PURPOSE: This study aimed to investigate the effects of two different positions on lower extremity hemodynamics during robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer. METHODS: A total of 196 patients who underwent RARP in our hospital from February 2020 to March 2022 were included in this study. Among them, 98 patients who underwent surgery with the Trendelenburg position and split-leg position with calf reverse arch from March 2021 to March 2022 were assigned to the observation group, while 98 patients who underwent surgery with the Trendelenburg position and low lithotomy position from February 2020 to February 2021 were assigned to the control group. Using an ultrasound diagnostic instrument to detect the internal diameter, mean blood flow velocity, and mean blood flow volume of the left deep femoral vein at different times, such as the supine position (T0), after 5 minutes of placing the patient in the leg spilt or low lithotomy position (T1), after 5 minutes of pneumoperitoneum (T2), after 5 minutes of head-down tilt or head-down tilt and calf reverse arch (T3), 1.5 hours after the start of surgery (T4), before the removal of CO2 gas (T5), and before the patient left the operating room (T6). As well as the patency of deep venous blood flow in both lower extremities before leaving the operating room, RESULTS: After establishment of pneumoperitoneum, the internal diameter of the deep femoral vein increased significantly, while the mean blood flow velocity and mean blood flow volume decreased significantly in both groups(T0) (P<0.001). With the prolongation of surgical time, the impact on lower extremity hemodynamics in the observation group was smaller than that in the control group. From T2 to T6, the internal diameter of the femoral vein in the observation group was smaller than that in the control group, while the mean blood flow velocity and mean blood flow volume were increased compared to the control group (P<0.05). Before leaving the operating room, the patency of deep venous blood flow in the observation group was better than that in the control group (P=0.003). CONCLUSION: Placing patients in the Trendelenburg position and split-leg position with calf reverse arch during RARP for prostate cancer has a smaller impact on lower extremity hemodynamics than the low lithotomy position, and can relatively reduce the risk of postoperative deep vein thrombosis.


Laparoscopy , Pneumoperitoneum , Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Hemodynamics/physiology , Prostatectomy , Lower Extremity , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery
19.
Prostate ; 84(8): 780-787, 2024 Jun.
Article En | MEDLINE | ID: mdl-38558415

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.


Prostate , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostate/pathology , Prostate/diagnostic imaging , Middle Aged , Aged , Organ Size , Biopsy , Unnecessary Procedures/statistics & numerical data , Retrospective Studies , Diffusion Magnetic Resonance Imaging/methods , ROC Curve
20.
World J Urol ; 42(1): 217, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38581590

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.


Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Early Detection of Cancer , Reproducibility of Results , Retrospective Studies , Prostate-Specific Antigen , Biopsy , Magnetic Resonance Imaging/methods , Neoplasm Grading , Image-Guided Biopsy
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