Gleason Score Research Articles

Weakly supervised deep learning for diagnosis of prostate cancer after radical prostatectomy: a population- based, multicenter study

Abstract Introduction/Objective The pathological diagnosis of prostate cancer after radical prostatectomy (RP) is a challenging and time-consuming process. Artificial intelligence has the potential to enhance this situation significantly. Our study aimed to assess the efficacy of weakly supervised deep learning, specifically focusing on practical diagnostic tasks for RP specimens. Methods/Case Report We obtained slices from clinical centers across four regions in China. The model was developed based on a multiple instance learning framework. We evaluated the model’s predictive accuracy, covering both slice-level and lesion-level diagnoses. Additionally, we investigated lesion localization using attention visualization. Slice-level diagnosis included prostate cancer detection and Gleason grading, while lesion-level diagnosis involved recognizing index lesions and non-index lesions. Results (if a Case Study enter NA) The study involved 13,245 slides from 304 patients. The area under the curve values in four validation sets ranged from 0.921 (95% CI 0.913–0.930) to 0.964 (95% CI 0.959–0.968). Regarding Gleason grading, the model demonstrated quadratic Weighted Kappa values of 0.748 and 0.720 for internal and external validation, respectively. The model predicted 1,683 (35.3%) positive and 3,081 (64.7%) negative slices in all validation sets. The median area of index lesions and non-index lesions was 92.6mm2 (IQR: 54.2–130.0mm2) and 3.5mm2 (IQR: 1.4–10.9mm2) (p<0.001), respectively. The model accurately predicted index lesions in all cases for three validation sets. Furthermore, the model achieved 100% accuracy in predicting slides with the maximum tumor area for index lesions in two validation sets. In visual assessment, 200 randomly selected slices predicted as true positive demonstrated that the model could identify 97.5% (195/200) of the index lesions. Conclusion The weakly supervised deep learning model demonstrated remarkably high diagnostic and localization capabilities in identifying index lesions within RP specimens. This targeted approach would effectively alleviate the diagnostic workload associated with pathology assessments for prostate cancer.

Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.

Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma. Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses. In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05). Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.

Comparative Study of Gleason 7 (3+4) and (4+3) Prostatic Adenocarcinomas with Prog-nostic Criteria and Immunohistochemical Profiles of AMACR, PSA and Ki-67.

To compare Gleason 7 (3+4) and (4+3) prostatic adenocarcinoma (PC) with different prognostic criteria through immunohistochemical analysis with anti-PSA, anti-Ki 67 and anti-AMARC antibodies. We analyzed 221 surgical specimens from patients between 40 and 86 years-old (mean=63) with PC. The immunohistochemical study was performed with anti-PSA, anti-Ki 67 and anti-AMARC. The microscopic fields were photographed with an Olympus DP70 digital camera coupled to an Olympus BX51 microscope and archived in TIFF. Proportion and intensity criteria were used to quantify the anti-PSA antibody and for the anti-Ki 67 antibody, the quantification by similarity of this antibody in breast carcinomas. Anti-AMACR protein expression was based on four scores: negative, weak, moderate and strong. The statistical analysis was performed with the Graph Pad Prism 5 program. In the Gleason score 7 (3+4) we had 91.72% in pT2 and 8.27% in the pT3 group; 8.27% recurrences, of which 90.90% in the pT2 group. In the Gleason score 7 (4+3) we had 77.27% in the pT2 group and 22.72% in the pT3 group and 10.22% of relapses, of which 66.66% in the pT2 group and 33.33% in the pT3 group. In 6.81% of cases there was an increase in the anti-Ki 67 index and in 2.27% of the cases, there was an increase in the immunoexpression of anti-p53 when comparing Gleason score 7 (3+4) with Gleason score 7 (4+3). Our study confirmed differences in the Gleason score 7 (3+4) and Gleason score 7 (4+3) of PC when comparing prognostic criteria. Anti-Ki 67 and anti-PSA antibody immunostaining showed a positive correlation as the Gleason score 7 increased from (3+4) to (4+3).

Targeted Biopsy Is Sufficient for Men on Active Surveillance for Early-Stage Prostate Cancer.

Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling. Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed. Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes. In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Prognostic Outcomes and Predictive Factors in Non-Metastatic Castration-Resistant Prostate Cancer Patients Not Treated with Second-Generation Antiandrogens.

Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC.

ANALYSIS OF CD10 EXPRESSION IN PROSTATE ADENOCARCINOMA AND ITS CORRELATION WITH DIFFERENT CLINICOPATHOLOGICAL PARAMETERS AT RNTMC, UDAIPUR

Objective: The study aimed to analyze the expression of CD10 in prostate adenocarcinoma to aid in early diagnosis and anti-CD10 targeted therapy. Methods: This was a cross-sectional study conducted in the Histopathology section of the Department of Pathologyat RNTMC, Udaipur, after approval from the ethical committee and institutional review board. This study was conducted on 92 patients suspected to have prostate cancer. The cases were assessed for Gleason score, Gleason Grade, and Serum Prostate Specific Antigen (PSA) levels. We performed IHC detection of CD10 in prostatic specimens and correlated the various patterns of CD10 expression concerning histopathological diagnosis. Results: In our study, we found membranous expression in low-grade carcinomas with low Gleason score and grade. The high-grade carcinomas with high Gleason score and Grade predominantly showed cytoplasmic expression. The increased CD10 cytoplasmic expression was correlated with serum PSA level. Conclusion: In our study, CD10 was found to be relevant. The low-grade carcinomas showed membranous positivity and high-grade carcinomas showed cytoplasmic expression. One hypothesis states that cytoplasmic expression is due to the localization of CD10 in the cytoplasm. Our study favors this hypothesis as there is cytoplasmic expression in high-grade tumors. In the future, this could be used as a diagnostic marker.

NFYA-mediated promotion of castration-resistant prostate cancer progression through EGR4 regulation

This research investigates the intricate involvement of nuclear Transcription Factor Y Subunit Alpha (NFYA) in the advancement of castration-resistant prostate cancer (CRPC) and its consequential impact on early Growth Response 4 (EGR4) expression. NFYA demonstrates a significant elevation in CRPC tissues and cell lines, displaying robust upregulation in metastatic prostate cancer (mPCa) samples, closely associated with the Gleason score. Immunohistochemistry validates heightened nuclear staining of NFYA in CRPC patients, highlighting its crucial role in the progression of advanced prostate cancer. Silencing NFYA through siRNA in androgen-independent cell lines markedly impedes cell growth and migration, emphasizing NFYA’s pivotal role in promoting CRPC behavior. RNA-seq analysis identifies EGR4 as a downstream target of NFYA, with both genes consistently upregulated in CRPC. Validating this finding, heightened expression of EGR4 is observed in CRPC samples. In vivo studies utilizing a mouse model demonstrate that NFYA silencing substantially inhibits LNCaP-AI/22RV1shNFYA xenograft tumor growth, accompanied by reduced expression of EGR4 and Ki67. This comprehensive study reveals the multifaceted role of NFYA in CRPC progression, elucidates its downstream impact on EGR4, and underscores the therapeutic potential of targeting NFYA to inhibit CRPC growth in vivo. These findings contribute valuable insights into potential therapeutic strategies for managing CRPC.

12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells

Abstract Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None. Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies. Presentation: 6/1/2024

Serum ACSL4 levels in prostate cancer patients and its relationship between patient prognosis: A prospective observational study.

In this prospective observational study, our objective was to investigate the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in prostate cancer (PCa) patients and examine its association with other serum biomarkers, and the clinical outcomes of PCa patients. This prospective observational study was conducted from January 2019 to October 2021, including 103 cases of PCa patients and 101 cases of benign prostate hyperplasia (BPH) patients who received treatment at our hospital. All patients had their serum ACSL4 levels measured using enzyme-linked immunosorbent assay before treatment. The clinical outcomes included age, body mass index, gender, systolic blood pressure, diastolic blood pressure, tumor node metastasis stage, Gleason scores, and prostate volume and serum biomarkers were collected. All patients were followed up for 36 months, the overall survival and disease-free survival were recorded for all patients. All data used SPSS 26.0 for analysis. The phosphorus (P) and serum low-density lipoprotein cholesterol levels were significantly higher in PCa patients compared to BPH patients. Furthermore, compared to the BPH patients, the serum ACSL4 and free prostate-specific antigen levels were significantly decreased while serum total prostate-specific antigen (tPSA) levels were significantly elevated in PCa patients. Pearson correlation analysis showed a positive correlation between ACSL4 levels and free prostate-specific antigen levels, while a negative correlation was observed with P and tPSA levels. ACSL4 might serve as a biomarker for diagnosing PCa with the AUC was 0.747, cutoff value of 33.68 ng/mL, sensitivity of 70.3%, and specificity of 60.2%. Finally, we found that ACSL4, tPSA, and P were identified as risk factors associated with PCa patients. Our findings indicated that the serum levels of ACSL4 were significantly decreased in PCa patients compared to BPH patients. Serum ACSL4 could be used as a potential biomarker for early PCa diagnosis and prognosis.

Histopathological Study Of Prostate Cancer According To Gleason Score

The aim of this study was to histopathological alternation prostate cancer according Gleason systems . The total number of study samples was (60 ) that taken from men who suffered prostate cancer .patients diagnosed by a specialist doctor. Blood samples taken from all groups for estimation of levels of PSA. Second type of samples was biopsy and paraffin block that taken from PC patients for detection of histopathological alternations depending Gleason score. The result obtained from histopathology method that the prostate cancer in early stage poorly differentiated gland to loss gland formation in advanced early stage.

B-321 Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50

Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital's prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusions Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.

B-332 Use of urinary volatile organic compounds in monitoring prostate cancer after radical prostatectomy

Abstract Background Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer among males and the second cause of cancer-related deaths. PCa treatment involves different methods, and most common is radical prostatectomy (RP), which entails removal of prostate-gland from men who have been diagnosed with PCa. Prostatic-specific-antigen (PSA) has been used for detection of recurrent disease for years. After its introduction as biochemical recurrence (BCR) marker, men with distinct diseases were treated similarly. Overtime, it has been observed that PSA relapse presents several meanings according to clinicopathological features, like Gleason score, PSA-doubling-time, clinical stage, surgical margin status. Despite this, PSA remains main tool to assess disease progression after RP. RP remains primary treatment for localized PCa and has been performed for years with excellent oncologic control. However, approximately 20-40% of patients with clinically localized PCa will present biochemical-recurrence (BCR) after RP, while some with recurrent-metastasis. The study aims to investigate potential volatile organic compounds (VOCs) associated with men who have undergone RP but still abhor the disease. Methods Urine samples were collected from 110 male adults with biopsy-proven PCa-positive results before and after RP. VOCs in urine were extracted by stir-bar-sorptive-extraction and analyzed using thermal-desorption with gas chromatography-mass spectrometry. Metabolomics and machine-learning tools used to develop and evaluate models for PCa diagnosis before and after RP. Results PLS-DA and VIP loading plots identified potential VOC panels that could be used to differentiate PCa patients before and after RP and those with BCR and recurrent metastasis. Furthermore, logistic-regression results with validation provide a promising diagnostic model for PCa diagnosis after RP. Conclusions This novel method using urinary VOCs was developed to fill gaps in PCa monitoring after RP. These research findings could aid and fast-track the provision of rapid point of care to the treated PCa patients who still abhor the disease.

Low level exposure to BDE-47 facilitates the development of prostate cancer through TOP2A/LDHA/lactylation positive feedback circuit

2,2′,4,4′-tetra brominated diphenyl ether (BDE-47) is one of the most widely distributed congeners of polybrominated diphenyl ethers. While the relationships between BDE-47 exposure and other hormone-dependent cancers (such as breast cancer) are well established, no previous study has examined whether BDE-47 exposure is related to the development of prostate cancer (PCa). Through bulk and single-cell RNA sequencing (scRNA-seq) analyses, as well as in vitro and in vivo experiments, this study aims to investigate the effect of BDE-47 exposure on PCa progression. Herein, we found that low dose BDE-47 promoted the growth of PCa cells (PC3 and LNCaP) in a dose-dependent manner in vitro and in vivo. Based on Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA), we obtained 34 BDE-47-related and PCa-related genes through screening and overlapping. These genes were significantly enriched in fatty acid metabolism-related gene ontology (GO) terms, which were also enriched for genes targeting BDE-47 obtained from the UniProt. Through scRNA-seq data, certain cell type-specific expression was observed for CYP2E1, PIK3R1, FGF2, and TOP2A in PCa tissues from men. Molecular docking simulation showed that BDE-47 was tightly bound to the protein residues of AOX1, PIK3R1, FGF2, CAV2, CYP2E1 and TOP2A. Further screening in terms of patient overall survival, receiver operating characteristics curve (ROC) curve and Gleason score grading system narrowed the candidate genes down to TOP2A. Mechanistically, the growth-promoting effect of BDE-47 on PCa cells could be reversed by TOP2A inhibitor. RNA-seq followed by experimental verification demonstrated that TOP2A promoted PCa progression through upregulating LDHA and glycolysis. Furthermore, lactate upregulated TOP2A transcription through lactylation of H3K18la in PCa cells, which could be rescued by LDHA knockdown. Taken together, low dose BDE-47 triggered PCa progression through TOP2A/LDHA/lactylation positive feedback circuit, thus revealing epigenetic shifting and metabolic reprogramming underpinning BDE-47-induced carcinogenesis of the prostate.

Clinicopathological Study of Prostate Diseases and Its Correlation with PSA Level, Size of Prostate and Gleason’s Scoring System in Case of Prostatic Carcinoma

Background: Prostate gland diseases significantly impact adult males globally, with an increasing prevalence due to aging populations. The primary conditions affecting the prostate are inflammation, benign prostatic hyperplasia (BPH), and tumors, with BPH being the most common. Prostatic carcinoma is also prevalent, with a high lifetime risk. Prostate cancer incidence increases with age, and early detection relies on digital rectal examination, transrectal ultrasonography, and PSA testing. Aim of the study: The study aims to find out correlation between PSA, Gleasons scoring system and HER-2/NEU gene in prostatic cancer. Methods: This study, conducted from July 2017 to June 2019 at BIRDEM General Hospital, enrolled 110 male patients aged 50-100 with clinical signs of prostatic diseases. Patients provided written informed consent and met specific inclusion criteria. Specimens were obtained via TURP, simple or radical prostatectomy, preserved in 10% neutral buffered formalin and examined for pathological lesions. PSA levels were measured using an immunoassay, and Gleason scoring was used for carcinoma categorization. Data were collected via questionnaires and analyzed using SPSS software. Result: The study analyzed 110 prostatic disease cases, with patients averaging 67.7 years. The most common diagnosis was BPH with inflammation (50.9%), followed by BPH without inflammation (35.5%) and adenocarcinoma (13.6%). Urgency (80%), increased micturition frequency (78.2%), poor stream (78.2%), and urinary retention (77.3%) were the most common symptoms. There was a significant correlation between serum PSA levels and prostate size (p &lt; 0.001), with higher PSA levels indicating larger prostates and a higher likelihood of adenocarcinoma. The most frequent Gleason score was 4+4=8 (40%). HER2/neu overexpression showed a marginal correlation with PSA levels (p=0.053). Conclusion: The study found that the most common age group for prostatic diseases was 61-70 years. Benign prostatic hyperplasia (BPH) was the most frequent lesion. Grade II (31-50g) prostate size was common on ultrasound. Most patients had a PSA level of 0-5 ng/ml, aiding early diagnosis and reducing morbidity

Loss of phosphatase and tensin homolog expression castration-sensitive prostate cancer predicts outcomes in men after prostatectomy.

This study aimed to investigate the potential for using the phosphatase and tensin homolog (PTEN) gene as a prognostic marker in post-prostatectomy patients with castration-sensitive prostate cancer (PCa). A total of 180 patients with castration-sensitive PCa who underwent radical prostatectomy at our institution were included in this study. PTEN expression was evaluated using immunohistochemistry, and patients were classified into two groups based on the staining intensity: PTEN-Normal and PTEN-Loss. The association between PTEN expression and biochemical recurrence was analyzed using the Cox proportional hazards model. Patients in the PTEN-Loss group had a higher risk of biochemical recurrence (hazard ratio, 4.642; 95% confidence interval, 2.137-10.083; p < 0.001) and a lower recurrence-free rate compared to the PTEN-Normal group (35% vs. 75%). In addition to clinicopathological factors, such as the serum prostate-specific antigen level, Gleason score, and T stage, evaluation of PTEN expression improved the prediction of biochemical recurrence after prostatectomy (area under the curve, 0.577 vs. 0.688). Low PTEN expression is a significant predictor of biochemical recurrence in patients with castration-sensitive PCa who have already undergone prostatectomy.

The effect of transvesical laparoscopic radical prostatectomy on sexual function and urinary continence

ObjectiveTo analyze the effect of transvesical laparoscopic radical prostatectomy (TVLRP) on sexual function and urinary continence.MethodThe data of 72 patients diagnosed with low-risk and localized prostate cancer, who underwent treatment at our hospital between January 2017 and June 2022, were retrospectively analyzed. All these patients underwent TVLRP under general anesthesia. Their serum prostate-specific antigen (PSA), urinary continence and erectile function were statistically analyzed.ResultsThe operation went well with no intraoperative difficulties. The average surgical duration of 102 ± 22 min, coupled with the minimal intraoperative blood loss of 100 ± 32 mL, underscored the precision and efficacy of the surgical techniques employed. Following surgery, postoperative pathological assessments confirmed staging, revealing pT2a in 18 cases and pT2b in 54 cases, suggestive of localized tumors. Gleason scores ≤ 6 further indicated well-differentiated tumors, while consistently negative surgical margins affirmed the complete resection of tumors, reducing the likelihood of disease recurrence. Subsequent to the surgical intervention, the the average hospital stay was 13.94.1 days. A comprehensive 12-month follow-up revealed exceptionally high urinary continence rates, with 97.8% and 100% of patients achieving continence at 1 and 3 months postoperatively, respectively. Moreover, progressive improvement in erectile function recovery was observed, with recovery rates at 3, 6, and 12 months postoperatively reaching 82.2%, 88.4%, and 93.5%, respectively. There was no biochemical regression.ConclusionTreatment of low-risk and localized prostate cancer by TVLRP has a satisfactory urinary continence and recovery of erectile function after operation, less and complications and definite tumor-control effect.

Unlocking Precision Enhancing Prostate Cancer Detection and Reducing Unnecessary Biopsies with Combined Prostate-Specific Antigen Density and PI-RADS Score.

To determine clinically significant prostate cancer (csPCa) detection rate by combining the prostate-specific antigen density (PSAD) and prostate imaging-reporting and data system (PI-RADS) scores. Descriptive study. Place and Duration of the Study: Department of Urology, University of Health Sciences, Ankara Oncology Training and Research Hospital, from January 2018 to April 2023. Patients who underwent prostate biopsies after multiparametric magnetic resonance imaging (mpMRI) were included in the study. PI-RADS 4 and 5 lesions were considered as MR positive. The cut-off values for PSAD were also determined to evaluate csPCa. csPCa detection rates were evaluated by grouping the patients based on the PSAD and mpMRI findings. PSAD cut-off value of 0.165 ng/mL/mL (sensitivity 80%, specificity 72%) was detected to predict csPCa (AUC = 0.81, 95% CI:0.756-0.866, p<0.001). csPCa detection rate was low (3%) in patients who have low PI-RADS scores (1-3) and a PSAD <0.165 ng/mL/mL. On the other hand, csPCa detection rate was high (50.5%) in patients who have a high PI-RADS score (4-5 lesions) and with a PSAD ≥0.165 ng/mL/mL. csPCa detection rates are low in patients with PI-RADS 1-3 lesions and low PSAD values. Unnecessary biopsy may be avoided in these patients. Gleason score, PI-RADS, Prostate cancer, Prostate-specific antigen, Prostate-specific antigen density.

Prospective Evaluation of Supplemental External Beam Radiation Therapy With Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44/20/0 Trials

PurposeThe 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy impacted biochemical failure (BF). We report long-term outcomes of both trials, and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort. Materials/methodsBoth trials enrolled patients with clinical T1c-T2b, Gleason score 7-9 and/or a pre-treatment prostate-specific antigen (PSA) 10-20 ng/ml disease. The 44/20 trial randomized patients to 44Gy EBRT with 90Gy palladium (Pd)-103 versus 20Gy EBRT with 115Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20Gy arm versus monotherapeutic 125Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether treatment arm was associated with BF for the entire cohort and the unfavorable intermediate risk (UIR) subgroup. For the combined trial cohort, multivariate Fine-Gray analysis evaluated whether BED was associated with BF, while adjusting for clinical factors. ResultsThere were 247 analyzable patients in the 44/20 trial. At a median follow-up of 13.7 years, there were no differences in BF for the entire cohort (sub-distribution hazard ratio (sHR) 0.99; 95% CI: 0.43, 2.276; p = 0.97) or the UIR subgroup (sHR 0.72; 95% CI: 0.25, 2.08; p = 0.55). There were 383 analyzable patients in the 20/0 trial. At a median follow-up of 10.4 years, there were no differences in BF for the entire cohort (sHR 0.42; 95% CI: 0.13-1.80; p = 0.15) or the UIR subgroup (sHR 0.81; 95% CI: 0.16-4.03; p = 0.80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI: 0.98-1.02; p = 0.88) on multivariate analyses, while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment. ConclusionsBrachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate risk prostate cancer, including UIR disease.

Evaluating Biparametric Versus Multiparametric Magnetic Resonance Imaging for Diagnosing Clinically Significant Prostate Cancer: An International, Paired, Noninferiority, Confirmatory Observer Study

Background and objectiveBiparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis. MethodsAn observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3–5) and a patient-level suspicion score (0–100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard. Key findings and limitationsSixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819–0.887) and 0.859 (95% CI, 0.826–0.893), respectively, with a noninferior difference of –0.6% (95% CI, –1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8–92.3%) and 89.4% (95% CI, 85.8–93.1%), respectively, with a noninferior difference of –0.9% (95% CI, –1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3–63.1%) and 57.7% (95% CI, 52.3–63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0–1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order. Conclusions and clinical implicationsIt has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes.

Cribriform intraductal carcinoma of the prostate may be more aggressive than cribriform conventional/acinar prostatic adenocarcinoma

It remains to be determined if the prognostic value of cribriform morphology (Crib) associated with intraductal carcinoma of the prostate (IDC) is equivalent to that in conventional/acinar prostatic adenocarcinoma (CPA). We herein assessed radical prostatectomy findings and long-term oncologic outcomes in 732 men with Grade Group 2-4 CPA without any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of Crib within CPA and/or IDC: Cohort-1) no Crib (n=347; 47.4%); Cohort-2) Crib only in CPA (n=203; 27.7%); Cohort-3) Crib only in IDC (n=17; 2.3%); and Cohort-4) Crib in both CPA and IDC (n=165; 22.5%). Compared with that in CPA only (Cohort-2), Crib in both CPA and IDC (Cohort-4) was significantly associated with adverse histopathological features, including higher tumor grade/stage and larger tumor volume. Univariate analysis revealed significantly higher risks of postoperative recurrence in patients with Crib in IDC only [Cohort-3; hazard ratio (HR) 2.450, P=0.022] or both CPA and IDC (Cohort-4; HR=2.835, P<0.001) than in those with Crib in CPA only (Cohort-2), while the prognosis was analogous between Cohort-3 vs. Cohort-4 (P=0.913). In multivariable analysis [Crib in CPA only (Cohort-2) as a reference], Crib in IDC only (Cohort-3; HR=3.821, P=0.002) or both CPA and IDC (Cohort-4; HR=1.905, P=0.004) showed significantly worse recurrence-free survival. Compared with Crib in CPA only, its presence in both CPA and IDC was thus found to be independently associated with a poorer prognosis, suggesting a potentially greater clinical impact of Crib in IDC than in CPA.