Gleason Score Research Articles

Prognostic significance of invasive cribriform gland size and percentage in Gleason score 7 prostate adenocarcinoma.

Cribriform glands are linked to poorer outcomes in prostate adenocarcinoma. We aimed to assess the prognostic role of the percentage of cribriform glands and the size of the largest invasive cribriform gland in Gleason score 7 prostate adenocarcinomas. The presence, percentage, and size of the invasive cribriform glands were investigated and their association with prognostic factors were assessed in 177 Grade Groups 2 and 3 prostate adenocarcinomas. Biochemical recurrence-free survival was statisticallysignificantly lower in cases with a cribriform gland percentage greater than 10% (P<.001) and in cases where the largest invasive cribriform gland size was greater than 0.5mm (P<.001). Mean largest cribriform gland size and percentage were statisticallysignificant associated with more advanced pT status, lymph node metastasis, biochemical recurrence, and higher preoperative prostate-specific antigen values. Our findings suggest that the presence of a cribriform pattern, increases in the percentage of such patterns, and increases in the size of the largest cribriform gland within a given tumor are associated with poor prognosis. We suggest that a more aggressive clinical approach may be needed in Grade Group 2 and 3 cases with invasive cribriform glands larger than 0.5mm and a cribriform gland percentage greater than 10%, especially in prostate needle biopsy specimens.

Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

A cross-species analysis of fecal microbiomes in humans and mice reveals similarities and dissimilarities associated with prostate cancer risk.

Prostate cancer is a complex disease that develops over time and is influenced by several lifestyle factors that also impact gut microbes. Gut dysbiosis is intricately linked to prostate carcinogenesis, but the precise mechanisms remain poorly understood. Mice are crucial for studying the relationships between gut microbes and prostate cancer, but discovering similarities between humans and mice may aid in elucidating new mechanisms. We used 16s rRNA sequencing data from stool samples of tumor-bearing prostate-specific conditional Pten-knockout mice, disease-free wildtype mice, and a human cohort suspected of having prostate cancer to conduct taxonomic and metagenomic profiling. Features were associated with prostate cancer status and low risk (a negative biopsy of Gleason grade <2) or high risk (Gleason grade ≥2) in humans. In both humans and mice, community composition differed between individuals with and without prostate cancer. Odoribacter spp. and Desulfovibrio spp. were taxa associated with prostate cancer in mice and humans. Metabolic pathways associated with cofactor and vitamin synthesis were common in mouse and human prostate cancer, including bacterial synthesis of folate (vitamin B9), ubiquinone (CoQ10), phylloquinone (vitamin K1), menaquinone (vitamin K2), and tocopherol (vitamin E). Our study provides valuable data that can help bridge the gap between human and mouse microbiomes. Our findings provide evidence to support the notion that certain bacterial-derived metabolites may promote prostate cancer, as well as a preclinical model that can be used to characterize biological mechanisms and develop preventive interventions.

Prostate Type Malignancies Arising in Ovarian Teratomas - A Report of Two Patients.

The identification of benign prostatic tissue within ovarian and testicular mature teratomas is an unusual occurrence. While a few documented reports exist in the literature regarding the emergence of benign prostatic tissue within teratomas, the occurrence of prostatic-type adenocarcinoma in a mature ovarian teratoma is an exceptionally rare phenomenon. To date, only two prior reports have documented such instances, and no tumors have been previously reported with prostate-type tissue with morphologically two different malignancies. We outline our experience with two tumors involving prostatic-type carcinoma, both arising in ovarian mature teratomas. Microscopic examination of the first tumor revealed small areas of infiltrative atypical glandular proliferation within the mature teratoma. In the second tumor, prostate-type tissue exhibited a low-grade basal cell carcinoma. Additionally, adjacent minute foci of adenocarcinoma of the prostate (Gleason score 3 + 4 = 7, <5% pattern 4) were identified. Goblet cell adenocarcinoma of appendiceal type was also evident in the latter tumor. In both tumors, immunostains (NKX3.1, PSA) were performed to establish the prostatic origin of these atypical glands and PIN4 was performed to document the absence of basal cell in the atypical glands. On clinical follow-up, both patients have no signs of recurrence at 14 and 11 months after the surgery. Further reports on such neoplasms would contribute to a better understanding of the prognosis and management of such occurrences.

Investigating Combination Therapy: The Role of Lutetium-177 PSMA-617 Radioligand Therapy and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan-Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28-0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33-1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients.

Utility of dynamic contrast enhancement for clinically significant prostate cancer detection.

This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms. We identified a retrospective cohort of biopsy naïve patients who underwent pre-biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3-5 on diffusion weighted imaging (DWI) with available DCE (annotated as - or +). bpMRI Prostate Imaging Reporting and Data System (PIRADS) (3 = 3-, 3+; 4 = 4-, 4+; 5 = 5-, 5+) and mpMRI PIRADS (3 = 3-; 4 = 3+, 4-, 4+; 5 = 5-, 5+) approaches were compared in multivariable logistic regression models. Nomograms for detection of csPCa and ≥GG3 PCa incorporating all biopsy naïve patients who underwent prostate MRI were generated based on available serum biomarkers [PHI, % free prostate-specific antigen (PSA), or total PSA] and validated with an independent cohort. Patients (n = 1010) with highest PIRADS lesion in PZ were included in initial analysis with 127 (12.6%) classified as PIRADS 3+ (PIRADS 3 on bpMRI but PIRADS 4 on mpMRI). On multivariable analysis, PIRADS 3+ lesions were associated with higher csPCa rates compared to PIRADS 3- (3+ vs. 3-: OR 1.86, p= 0.024), but lower csPCa rates compared to PIRADS DWI 4 lesions (4 vs. 3+: OR 2.39, p< 0.001). csPCa rates were 19% (3-), 31% (3+), 41.5% (4-), 65.9% (4+), 62.5% (5-), and 92.3% (5+). bpMRI nomograms were non-inferior to mpMRI nomograms in the development (n= 1410) and independent validation (n= 353) cohorts. Risk calculators available at: https://rossnm1.shinyapps.io/MynMRIskCalculator/. While DCE positivity by itself was associated with csPCa among patients with highest PIRADS lesions in the PZ, nomogram comparisons suggest that there is no significant difference in performance of bpMRI and mpMRI. bpMRI may be considered as an alternative to mpMRI for prostate cancer evaluation in many situations.

Detection of differentially methylated CpGs between tumour and adjacent benign cells in diagnostic prostate cancer samples

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.

The value of synthetic magnetic resonance imaging in the diagnosis and assessment of prostate cancer aggressiveness.

Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA). We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples). The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001). Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy.

Final Results of the ANDROCAN Study: Histopathological Characteristics and Biochemical Recurrence at 5 Years of Localized Prostate Cancer According to Preoperative Gonadal Status

Background and objectiveFailure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status. MethodsA prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis. Key findings and limitationsAmong the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates. Conclusions and clinical implicationsOverall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up. Patient summaryFive-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection.

Establishment of a prognostic risk model for prostate cancer based on Gleason grading and cuprotosis related genes

IntroductionProstate cancer (PCa) is common in aging males, diagnosed via the Gleason grading system. The study explores the unexamined prognostic value of cuprotosis, a distinct cell death type, alongside Gleason grades in PCa.MethodsWe explored Cuprotosis-related genes (CRGs) in prostate cancer (PCa), using NMF on TCGA-PRAD data for patient classification and WGCNA to link genes with Gleason scores and prognosis. A risk model was crafted via LASSO Cox regression. STX3 knockdown in PC-3 cells, analyzed for effects on cell behaviors and tumor growth in mice, highlighted its potential therapeutic impact.ResultsWe identified five genes crucial for a prognostic risk model, with higher risk scores indicating worse prognosis. Survival analysis and ROC curves confirmed the model’s predictive accuracy in TCGA-PRAD and GSE70769 datasets. STX3 was a key adverse prognostic factor, with its knockdown significantly reducing mRNA and protein levels, impairing PC-3 cell functions. In vivo, STX3 knockdown in PC-3 cells led to significantly smaller tumors in nude mice, underscoring its potential therapeutic value.ConclusionOur prognostic model, using five genes linked to Gleason scores, effectively predicts prostate cancer outcomes, offering a novel treatment strategy angle.

Utility of 64Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on 68Ga-PSMA-11 PET/CT.

Despite a high detection rate of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative 68Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog 64Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of 64Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal 68Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal 68Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. 64Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of 64Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4-11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28-2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). 64Cu-SAR-BBN PET-avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16-0.82). Patients were followed up for a median of 10 mo (IQR, 9-12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: 64Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.

NAT10 Promotes Prostate Cancer Growth and Metastasis by Acetylating mRNAs of HMGA1 and KRT8.

N4-acetylcytidine (ac4C) is essential for the development and migration of tumor cells. According to earlier research, N-acetyltransferase 10 (NAT10) can increase messenger RNAs (mRNAs) stability by catalyzing the synthesis of ac4C. However, little is known about NAT10 expression and its role in the acetylation modifications in prostate cancer (PCa). Thus, the biological function of NAT10 in PCa is investigated in this study. Compared to paraneoplastic tissues, the expression of NAT10 is significantly higher in PCa. The NAT10 expression is strongly correlated with the pathological grade, clinical stage, Gleason score, T-stage, and N-stage of PCa. NAT10 has the ability to advance the cell cycle and the epithelial-mesenchymal transition (EMT), both of which raise the malignancy of tumor cells. Mechanistically, NAT10 enhance the stability of high mobility group AT-hook 1 (HMGA1) by acetylating its mRNA, thereby promoting cell cycle progression to improve cell proliferation. In addition, NAT10 improve the stability of Keratin 8 (KRT8) by acetylating its mRNA, which promotes the progression of EMT to improve cell migration. This findings provide a potential prognostic or therapeutic target for PCa.

Fully Automated Deep Learning Model to Detect Clinically Significant Prostate Cancer at MRI.

Background Multiparametric MRI can help identify clinically significant prostate cancer (csPCa) (Gleason score ≥7) but is limited by reader experience and interobserver variability. In contrast, deep learning (DL) produces deterministic outputs. Purpose To develop a DL model to predict the presence of csPCa by using patient-level labels without information about tumor location and to compare its performance with that of radiologists. Materials and Methods Data from patients without known csPCa who underwent MRI from January 2017 to December 2019 at one of multiple sites of a single academic institution were retrospectively reviewed. A convolutional neural network was trained to predict csPCa from T2-weighted images, diffusion-weighted images, apparent diffusion coefficient maps, and T1-weighted contrast-enhanced images. The reference standard was pathologic diagnosis. Radiologist performance was evaluated as follows: Radiology reports were used for the internal test set, and four radiologists' PI-RADS ratings were used for the external (ProstateX) test set. The performance was compared using areas under the receiver operating characteristic curves (AUCs) and the DeLong test. Gradient-weighted class activation maps (Grad-CAMs) were used to show tumor localization. Results Among 5735 examinations in 5215 patients (mean age, 66 years ± 8 [SD]; all male), 1514 examinations (1454 patients) showed csPCa. In the internal test set (400 examinations), the AUC was 0.89 and 0.89 for the DL classifier and radiologists, respectively (P = .88). In the external test set (204 examinations), the AUC was 0.86 and 0.84 for the DL classifier and radiologists, respectively (P = .68). DL classifier plus radiologists had an AUC of 0.89 (P < .001). Grad-CAMs demonstrated activation over the csPCa lesion in 35 of 38 and 56 of 58 true-positive examinations in internal and external test sets, respectively. Conclusion The performance of a DL model was not different from that of radiologists in the detection of csPCa at MRI, and Grad-CAMs localized the tumor. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Johnson and Chandarana in this issue.

Promoter Hypermethylation of the BRCA1 Gene as a Novel Biomarker for Prostate Cancer.

Prostate cancer (PCa) is recognized as one of the most common malignancies that greatly affects the male population globally. Breast cancer gene 1 (BRCA1) is an important tumor suppressor gene that plays a central role in the maintenance of genomic integrity by promoting the repair of double-strand breaks of DNA. Here, we present a pilot study to examine the promoter methylation and gene expression of the BRCA1 gene in patients with PCa in Erbil governorate, Iraq. The collection of samples took place in Erbil City, Iraq, specifically at Rizgary Hospital, PAR Hospital, and Al-Mufti's private laboratory. A total of 40 tissue samples were collected from age-matched individuals, comprising 30 pathologically confirmed PCa cases and 10 normal prostatic tissue taken from individuals who, during diagnosis, were found to be negative for PCa. Data on demographic and clinical information, such as pathological stage, age, and prostate-specific antigen (PSA) level, were gathered from the medical records. The impact of the promoter methylation was forecasted using the DNA bisulfite conversion technique and methyl-specific PCR (MSP) with specific primers for the BRCA1 promoter region. The assessment of BRCA1 expression was conducted using quantitative real-time PCR (qPCR). Among the 30 patients examined, 76.6% (23 cases) were found to have BRCA1 promoter methylation, and none of the normal tissues appeared to have DNA methylation. BRCA1 promoter methylation was positively associated with the advanced stage of disease (p=0.01) and Gleason score (p=0.007). The analysis revealed a significant downregulation of the BRCA1 gene expression in methylated tumor samples as compared to non-methylated tumors and normal tissues, suggesting the role of epigenetic silencing. To the best of our knowledge, this is the first study investigating methylation status and level of BRCA1 mRNA transcripts among PCa patients in Iraq. Our findings suggest that promoter hypermethylation of the BRCA1 gene could serve as a viable biomarker for PCa, marking a significant discovery.

Systematic Biopsy vs. Prostatectomy: Evaluating Correlations and Grading Discrepancies in Prostate Cancer.

Background Prostate Cancer (PCa) represents agrowing global health challenge. The main factor in predicting PCa prognosis is represented by the Gleason Score (GS)therefore, the accuracy of pathological features from preoperative biopsy is critical in the management of the patient. We aimed to investigate the correlation between prostate biopsy parameters and the prostatectomy specimen pathological features and to identify factors that lead to over- and under-grading tumors in biopsy samples. Materials and methods We performed a retrospective study that included 110 male patients with confirmed PCa, selected based on specific inclusion criteria. Biopsy and radical prostatectomy (RP) specimens were analyzed using standard histopathological techniques, and pathological features were assessed according to the latest guidelines. Statistical analysis was performed using IBM SPSS Statistics version 26.0.0 (IBM Corp., Armonk, NY). Results The study included 110 male patients with a median age of 67 years old, ranging from 48 to 79 years old. Correlations between biopsy parameters and RP outcomes were assessed and revealed several key findings. The tumoral length on biopsy was correlated with positive surgical margin (r=0.289, p<0.01) and with tumoral volume (r=0.526, p<0.001) on prostatectomy. Patients with higher grade groups (GG) on biopsy had an approximately four times higher chance of exhibiting extraprostatic extension. We demonstrated a significant correlation between Gleason Pattern 4 (%GP4) on biopsy and pT stage, with pT4 showing the highest %GP4, and a noticeable increase in %GP4 as the pT stage progressed from pT2b to pT4. The study found a significantly higher rate of undergrading at biopsy (30.90%) compared to overgrading (6.36%). Additionally, greater tumor length and higher tumor percentages in biopsies improved grading accuracy (p<0.001). Conclusion Our findings suggest that systemic biopsies play a key role in predicting pathological outcomes, especially through parameters that serve as key prognostic markers. However, due to the potential of the biopsy results to be under- or overgraded, urologists should take into consideration the advantages of using repeat biopsies or additional imaging techniques to achieve a more precise diagnosis and treatment strategy.

Long-term outcomes of the first prospective study of active surveillance for prostate cancer in Japan.

Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. This multicenter prospective observational cohort study enrolled men aged 50-80years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6months and every 3months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2years and pathological progression on repeat biopsy. Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70years, 6.5ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7years. At 1year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines.

Comparative Study Analysis of Epstein-Barr Virus Infection: Tissue Versus Blood Samples in Patients With Prostatic Adenocarcinoma and Its Correlation With Clinicopathological Parameters.

Prostate cancer (PCa) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality in men. The diagnosis and treatment of PCa carry considerable medical, psychological, and economic implications. Among the risk factors contributing to cancer, viral infections, notably Epstein-Barr virus (EBV), play a significant role. It is recognized as an oncogenic virus associated with various lymphomas, nasopharyngeal carcinomas, and breast cancer cases but its role in PCa remains unclear. This study aims to contrast the prevalence of EBV in blood and tissue samples of PCa patients and assess its correlation with tumor clinicopathological criteria. In this prospective study, 50 fresh biopsies and 50 blood samples were collected from patients with a confirmed diagnosis of PCa. EBV DNA was detected using polymerase chain reaction (PCR). A statistical analysis was then conducted to examine the correlation between EBV prevalence and PCa clinicopathological characteristics. EBV DNA was detected in 38% of PCa blood samples and 64% of PCa tissue samples, with a higher prevalence in tissue samples (p = 0.009). The statistical analysis revealed a significant correlation between EBV infection andpathological Gleason score (p = 0.041) in PCa tissue, as well as pathological T-stage (p = 0.02) in PCa blood. The results show that patients with PCa have higher levels of EBV in their tissues than in their blood, suggesting that EBV may play an important role in the etiology of PCa. This paves the way for further research into the function of EBV as a potential biomarker in the development and progression of prostate carcinoma in order to combatoncogenic viruses.

Establishing a model predicting Gleason grade group upgrading in prostate cancer.

Gleason grade group (GG) upgrading is associated with increased biochemical recurrence (BCR), local progression, and decreased cancer-specific survival (CSS) in prostate cancer (PCa). However, descriptions of the risk factors of GG upgrading are scarce. The objective of this study was to identify risk factors and establish a model to predict GG upgrading. There were 361 patients with PCa who underwent radical prostatectomy between May 2011 and February 2022 enrolled. Univariate and multivariate logistic regression analyses were identified and nomogram further narrowed down the contributing factors in GG upgrading. The correction curve and decision curve were used to assess the model. In the overall cohort, 141 patients had GG upgrading. But the subgroup cohort (GG ≤2) showed that 68 patients had GG upgrading. Multivariate logistic regression analysis showed that in the overall cohort, total prostate-specific antigen (tPSA) ≥10 ng/mL, systemic immune-inflammation index (SII) >379.50, neutrophil-lymphocyte ratio (NLR) >2.13, the GG of biopsy ≥3, the number of positive cores >3 were independent risk factors in GG upgrading. In the cohort of biopsy GG ≤2, multivariate logistic regression showed that the tPSA ≥10 ng/mL, SII >379.50 and the number of positive cores >3 were independent risk factors in GG upgrading. A novel model predicting GG upgrading was established based on these three parameters. The area under the curve (AUC) of the prediction model was 0.759. The C-index of the nomogram was 0.768. The calibration curves of the model showed good predictive performance. Clinical decision curves indicated clinical benefit in the interval of 20% to 90% of threshold probability and good clinical utility. Combined levels of tPSA, SII and the positive biopsy cores distinguish patients with high-risk GG upgrading in the group of biopsy GG ≤2 and are helpful in the decision of treatment plans.

Machine learning predicts conventional imaging metastasis-free survival (MFS) for oligometastatic castration-sensitive prostate cancer (omCSPC) using prostate-specific membrane antigen (PSMA) PET radiomics

PurposeThis study investigated imaging biomarkers derived from PSMA-PET acquired pre- and post-metastasis-directed therapy (MDT) to predict 2-year metastasis-free survival (MFS), which provides valuable early response assessment to improve patient outcomes. Materials/MethodsAn international cohort of 117 oligometastatic castration-sensitive prostate cancer (omCSPC) patients, comprising 34 from John Hopkins Hospital (JHH) and 83 from Baskent University (BU), were treated with stereotactic ablative radiation therapy (SABR) MDT with both pre- and post-MDT PSMA-PET/CT scans acquired. PET radiomic features were analyzed from a CT-PET fusion defined gross tumor volume ((GTV) or zone 1), and a 5 mm expansion ring area outside the GTV (zone 2). A total of 1748 PET radiomic features were extracted from these zones. The six most significant features selected using the Chi2 method, along with five clinical parameters (age, Gleason score, number of total lesions, untreated lesions, and pre-MDT prostate-specific antigen (PSA)) were extracted as inputs to the models. Various machine learning models, including Random Forest, Decision Tree, Support Vector Machine, and Naïve Bayesian, were employed for 2-year MFS prediction and tested using leave-one-out and cross-institution validation. ResultsSix radiomic features, including Total Energy, Entropy, and Standard Deviation from pre-PSMA-PET zone 1, Total Energy and Contrast from post-PSMA-PET zone 1, and Entropy from pre-PSMA-PET zone 2, along with five clinical parameters were selected for predicting 2-year MFS. In a leave-one-out test with all the patients, random forest achieved an accuracy of 80 % and an AUC of 0.82 in predicting 2-year MFS. In cross-institution validation, the model correctly predicted 2-year MFS events with an accuracy of 75 % and an AUC of 0.77 for patients from JHH, and an accuracy of 78 % and an AUC of 0.80 for BU patients, respectively. ConclusionOur study demonstrated the promise of using pre- and post-MDT PSMA-PET-based imaging biomarkers for MFS prediction for omCSPC patients.

Unveiling the diagnostic potential of diffusion kurtosis imaging and intravoxel incoherent motion for detecting and characterizing prostate cancer: a meta-analysis.

This study aims to assess the diagnostic capabilities of Diffusion Kurtosis Imaging (DKI) and Intravoxel Incoherent Motion (IVIM) in prostate cancer (PCa) detection and characterization. A comprehensive search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library for articles published up to September 10, 2023, that evaluated the diagnostic efficacy of MD, MK, Dt, f, and Dp parameters. Data were pooled using a bivariate mixed-effects regression model and analyzed with R software. In total, 27 studies were included. The analysis revealed distinct diagnostic efficacies for DKI and IVIM. In the overall model, sensitivity and specificity were 0.807 and 0.797, respectively, with prospective studies showing higher specificity (0.858, p = 0.024). The detection model yielded increased sensitivity (0.845) and specificity (0.812), with DKI outperforming IVIM in both metrics (sensitivity: 0.87, p = 0.043; specificity: 0.837, p = 0.26); MD had high sensitivity (0.88) and specificity (0.82), while MK's specificity was significantly higher (0.854, p = 0.04); Dp's sensitivity was significantly lower (0.64, p = 0.016). In characterization, sensitivity and specificity were 0.708 and 0.735, respectively, with no significant differences between DKI and IVIM or Gleason Scores; MK had higher sensitivity (0.78, p = 0.039), and f's sensitivity was significantly lower (0.51, p = 0.019). In summary, the study underscores DKI's enhanced diagnostic accuracy over IVIM in detecting PCa, with MK standing out for its precision. Conversely, Dp and f lag in diagnostic performance. Despite these promising results, the study highlights the imperative for standardized protocols and study designs to achieve reliable and consistent outcomes.