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1.
Sci Data ; 11(1): 504, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755158

Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 177 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta AB, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.985.392 prostate and patient couch positions over a time span of 272 hours, 52 minutes and 34 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.


Prostate , Prostatic Neoplasms , Ultrasonography , Humans , Male , Movement , Prostate/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated
2.
Radiology ; 311(2): e231879, 2024 May.
Article En | MEDLINE | ID: mdl-38771185

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


Fluorine Radioisotopes , Multiparametric Magnetic Resonance Imaging , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Multiparametric Magnetic Resonance Imaging/methods , Prospective Studies , Aged , Middle Aged , Niacinamide/analogs & derivatives , Oligopeptides , Radiopharmaceuticals , Prostate/diagnostic imaging , Sensitivity and Specificity
3.
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
4.
Int J Comput Assist Radiol Surg ; 19(5): 841-849, 2024 May.
Article En | MEDLINE | ID: mdl-38704793

PURPOSE: Deep learning-based analysis of micro-ultrasound images to detect cancerous lesions is a promising tool for improving prostate cancer (PCa) diagnosis. An ideal model should confidently identify cancer while responding with appropriate uncertainty when presented with out-of-distribution inputs that arise during deployment due to imaging artifacts and the biological heterogeneity of patients and prostatic tissue. METHODS: Using micro-ultrasound data from 693 patients across 5 clinical centers who underwent micro-ultrasound guided prostate biopsy, we train and evaluate convolutional neural network models for PCa detection. To improve robustness to out-of-distribution inputs, we employ and comprehensively benchmark several state-of-the-art uncertainty estimation methods. RESULTS: PCa detection models achieve performance scores up to 76 % average AUROC with a 10-fold cross validation setup. Models with uncertainty estimation obtain expected calibration error scores as low as 2 % , indicating that confident predictions are very likely to be correct. Visualizations of the model output demonstrate that the model correctly identifies healthy versus malignant tissue. CONCLUSION: Deep learning models have been developed to confidently detect PCa lesions from micro-ultrasound. The performance of these models, determined from a large and diverse dataset, is competitive with visual analysis of magnetic resonance imaging, the clinical benchmark to identify PCa lesions for targeted biopsy. Deep learning with micro-ultrasound should be further studied as an avenue for targeted prostate biopsy.


Deep Learning , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , Image-Guided Biopsy/methods , Ultrasonography/methods , Neural Networks, Computer , Ultrasonography, Interventional/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.
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
7.
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.
Int J Mol Sci ; 25(10)2024 May 15.
Article En | MEDLINE | ID: mdl-38791417

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.


Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Middle Aged , Aged , Receptors, Androgen/genetics , Neoplasm Grading , Magnetic Resonance Imaging/methods , Biopsy , Phenotype , ROC Curve , DNA Copy Number Variations/genetics
10.
J Int Med Res ; 52(5): 3000605241253756, 2024 May.
Article En | MEDLINE | ID: mdl-38796313

Prostatic stromal tumors, encompassing prostatic sarcoma and stromal tumors of uncertain malignant potential (STUMP), represent an exceedingly rare category of prostatic diseases, with a prevalence of less than 1%. We present a rare case involving a man in his early 40s diagnosed with STUMP. Despite presenting with normal prostate-specific antigen (PSA) concentrations, the patient experienced persistent dysuria and gross hematuria for >7 months, leading to an initial misdiagnosis of benign prostatic hyperplasia. Persistent symptoms prompted further investigation, with magnetic resonance imaging (MRI) revealing a suspicious lesion on the left side of the prostate, initially thought to be malignant. Transrectal prostatic biopsy subsequently confirmed the presence of mucinous liposarcoma, with no medical history of diabetes, coronary heart disease, or hypertension. The treatment approach comprised robot-assisted laparoscopic radical prostatectomy, culminating in a postoperative pathological definitive diagnosis of STUMP. This case underscores the indispensable role of early MRI in the diagnostic process, highlighting the necessity of detailed pathological examination for a conclusive diagnosis. Our report aims to illuminate the diagnostic challenges and potential treatment pathways for STUMP, emphasizing its consideration in the differential diagnosis of prostatic tumors to advance clinical outcomes in this rare but important condition.


Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/diagnostic imaging , Adult , Diagnosis, Differential , Prostatectomy , Prostate/pathology , Prostate/surgery , Prostate/diagnostic imaging , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/diagnostic imaging , Prostatic Hyperplasia/diagnosis , Sarcoma/pathology , Sarcoma/surgery , Sarcoma/diagnosis , Sarcoma/diagnostic imaging
11.
Radiol Phys Technol ; 17(2): 504-517, 2024 Jun.
Article En | MEDLINE | ID: mdl-38691309

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer.


Fiducial Markers , Heavy Ion Radiotherapy , Movement , Patient Positioning , Prostatic Neoplasms , Radiotherapy Planning, Computer-Assisted , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Radiotherapy Planning, Computer-Assisted/methods , Radiometry , Radiotherapy Dosage , Prostate/radiation effects , Prostate/diagnostic imaging , Aged , Motion , Dose Fractionation, Radiation
12.
Curr Oncol ; 31(5): 2846-2855, 2024 05 16.
Article En | MEDLINE | ID: mdl-38785497

Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.


Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Middle Aged , Magnetic Resonance Imaging/methods , Prostatectomy/methods
13.
Radiol Imaging Cancer ; 6(3): e230143, 2024 May.
Article En | MEDLINE | ID: mdl-38758079

Purpose To develop and validate a machine learning multimodality model based on preoperative MRI, surgical whole-slide imaging (WSI), and clinical variables for predicting prostate cancer (PCa) biochemical recurrence (BCR) following radical prostatectomy (RP). Materials and Methods In this retrospective study (September 2015 to April 2021), 363 male patients with PCa who underwent RP were divided into training (n = 254; median age, 69 years [IQR, 64-74 years]) and testing (n = 109; median age, 70 years [IQR, 65-75 years]) sets at a ratio of 7:3. The primary end point was biochemical recurrence-free survival. The least absolute shrinkage and selection operator Cox algorithm was applied to select independent clinical variables and construct the clinical signature. The radiomics signature and pathomics signature were constructed using preoperative MRI and surgical WSI data, respectively. A multimodality model was constructed by combining the radiomics signature, pathomics signature, and clinical signature. Using Harrell concordance index (C index), the predictive performance of the multimodality model for BCR was assessed and compared with all single-modality models, including the radiomics signature, pathomics signature, and clinical signature. Results Both radiomics and pathomics signatures achieved good performance for BCR prediction (C index: 0.742 and 0.730, respectively) on the testing cohort. The multimodality model exhibited the best predictive performance, with a C index of 0.860 on the testing set, which was significantly higher than all single-modality models (all P ≤ .01). Conclusion The multimodality model effectively predicted BCR following RP in patients with PCa and may therefore provide an emerging and accurate tool to assist postoperative individualized treatment. Keywords: MR Imaging, Urinary, Pelvis, Comparative Studies Supplemental material is available for this article. © RSNA, 2024.


Magnetic Resonance Imaging , Neoplasm Recurrence, Local , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/blood , Aged , Retrospective Studies , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/blood , Middle Aged , Prostatectomy/methods , Magnetic Resonance Imaging/methods , Machine Learning , Predictive Value of Tests , Multimodal Imaging/methods , Prostate-Specific Antigen/blood , Multiparametric Magnetic Resonance Imaging/methods
14.
World J Urol ; 42(1): 341, 2024 May 21.
Article En | MEDLINE | ID: mdl-38771329

BACKGROUND: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. METHODS: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. RESULTS: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. CONCLUSION: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.


Neoplasm Grading , Positron Emission Tomography Computed Tomography , Prostatectomy , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Retrospective Studies , Middle Aged , Aged , Prostatectomy/methods , Predictive Value of Tests , Prostate/pathology , Prostate/diagnostic imaging , Glutamate Carboxypeptidase II , Antigens, Surface , Biopsy
15.
Bioorg Med Chem ; 106: 117753, 2024 May 15.
Article En | MEDLINE | ID: mdl-38749342

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.


Antigens, Surface , Drug Design , Fluorine Radioisotopes , Positron-Emission Tomography , Radiopharmaceuticals , Animals , Humans , Male , Fluorine Radioisotopes/chemistry , Mice , Antigens, Surface/metabolism , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Glutamate Carboxypeptidase II/metabolism , Molecular Structure , Cell Line, Tumor , Neoplasms, Experimental/diagnostic imaging , Neoplasms, Experimental/metabolism , Structure-Activity Relationship
16.
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 , Aged , Humans , Male , Middle Aged , Magnetic Resonance Imaging/methods , Organ Sparing Treatments/methods , Organs at Risk/radiation effects , Prospective Studies , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Quality of Life , Radiosurgery/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Image-Guided/methods , Urinary Bladder/radiation effects , Clinical Trials, Phase II as Topic
17.
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 , Aged , Humans , Male , Biopsy/methods , Gallium Isotopes , Gallium Radioisotopes , Image-Guided Biopsy/methods , Nomograms , Positron Emission Tomography Computed Tomography/methods , Predictive Value of Tests , Prostate/pathology , Prostate/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Retrospective Studies , Risk Assessment
18.
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
19.
J Colloid Interface Sci ; 670: 585-598, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38776693

Whilst the development of advanced organic dots with aggregation-induced emission characteristics (AIE-dots) is being intensively studied, their clinical translation in efficient biotherapeutic devices has yet to be tackled. This study explores the synergistic interplay of oligo(styryl)benzenes (OSBs), potent fluorogens with an increased emission in the aggregate state, and Indocyanine green (ICG) as dual Near Infrared (NIR)-visible fluorescent nanovesicles with efficient reactive oxygen species (ROS) generation capacity for cancer treatment using photodynamic therapy (PDT). The co-loading of OSBs and ICG in different nanovesicles has been thoroughly investigated. The nanovesicles' physicochemical properties were manipulated via molecular engineering by modifying the structural properties of the lipid bilayer and the number of oligo(ethyleneoxide) chains in the OSB structure. Diffusion Ordered Spectroscopy (DOSY) NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the OSB and ICG in the bilayer. The in vitro assessment of these OSB-ICG nanovesicles revealed that the formulations can increase the temperature and generate ROS after photoirradiation, showing for the first time their potential as dual photothermal/photodynamic (PTT/PDT) agents in the treatment of prostate cancer. Our study provides an exciting opportunity to extend the range of applications of OSB derivates to potentiate the toxicity of phototherapy in prostate and other types of cancer.


Liposomes , Photochemotherapy , Prostatic Neoplasms , Reactive Oxygen Species , Male , Humans , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Liposomes/chemistry , Reactive Oxygen Species/metabolism , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Particle Size , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Cell Survival/drug effects , Benzene Derivatives/chemistry , Benzene Derivatives/pharmacology , Optical Imaging , Quantum Dots/chemistry , Surface Properties , Molecular Structure
20.
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
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