Gleason Score Research Articles

Risk of clinically significant prostate cancer undercategorized by multiparametric magnetic resonance imaging.

To investigative potential clinicopathological characteristics and imaging-related risk factors of clinically significant prostate cancer (csPCa) undercategorized in patients with negative or equivocal MRI. This retrospective study included 581 patients with pathologically confirmed csPCa (Gleason score ≥ 3 + 4), including 108 undercategorized csPCa and 473 detected csPCa. All patients underwent multiparametric MRI (mpMRI). The undercategorized csPCa was defined as a MRI result with PI-RADS ≤ 3. The clinicopathological characteristics and imaging-related factors were compared between the undercategorized group(Group A) (PI-RADS 1-3) and detected group (Group B) (PI-RADS 4-5). The age, total PSA levels, PSAD, free PSA, prostate imaging quality (PI-QUAL) scores, and Gleason scores were significantly lower in the Group A than Group B. The lesions were larger and involved in peripheral and transition zones in the Group B. A significant difference in the second reading opinion. Age (odds ratio [OR], 0.94), PSAD (OR, 0.09), and PI-QUAL scores (OR, 0.25) were significantly associated with the undercategorized csPCa. The rate of undercategorized csPCa with these three risk factors (age, PSAD, and PI-QUAL scores of < 71, < 0.355, and < 3, respectively) was 68.62%. The lack of zoomed-DWI resulted in lower PI-QUAL scores. Finally, the probability of undercategorized csPCa without zoomed DWI was 3.186 times higher than that with zoomed DWI when the PSAD ratio is lower than 0.355. Low image quality, younger age, and lower PSAD contribute to csPCa undercategorized by mpMRI. Moreover, the use of zoomed DWI decreased undercategorized csPCa by improving PI-QUAL scores of MRI images.

Constructing and Validating Models for Predicting Gleason Grade Group Upgrading Following Radical Prostatectomy in Localized Prostate Cancer: A Comparison between Machine Learning Algorithms and Conventional Logistic Regression

Constructing and Validating Models for Predicting Gleason Grade Group Upgrading Following Radical Prostatectomy in Localized Prostate Cancer: A Comparison between Machine Learning Algorithms and Conventional Logistic Regression

Discordance between prostate MRI and PSMA-PET/CT: the next big challenge for primary prostate tumor assessment?

An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of discordance between MRI and PSMA-PET/CT for primary PCa assessment. Consecutive men diagnosed with intermediate and high-risk PCa who underwent MRI and PSMA-PET/CT in 2021-2023 were retrospectively included. MRI and PSMA-PET/CT were interpreted using PI-RADS v2.1 and PRIMARY scores. Discordances between the two imaging modalities were categorized as "minor" (larger or additional lesion seen on one modality) or "major" (positive on only one modality or different index lesions between MRI and PSMA-PET/CT) and reconciled using radical prostatectomy or biopsy specimens. Three hundred and nine men (median age 69 years, interquartile range (IQR) 64-75) were included. Most had Gleason Grade Group ≥ 3 PCa (70.9% (219/309)). Median PSA was 9.0 ng/mL (IQR 5.6-13.6). MRI and PSMA-PET/CT were concordant in 157/309 (50.8%) and discordant in 152/309 (49.1%) patients; with 39/152 (25.7%) major and 113/152 (74.3%) minor discordances. Of 27 patients with lesions only seen on MRI, 85.2% (23/27) were clinically significant PCa (csPCa). Of 23 patients with lesions only seen on PSMA-PET/CT, 78.3% (18/23) were csPCa. Altogether, lesions seen on only one modality were csPCa in 80.0% (36/45). MRI and PSMA-PET/CT were discordant in half of patients for primary PCa evaluation, with major discrepancies seen in roughly one out of eight patients. Question While both MRI and PSMA-PET/CT can be used for primary tumor assessment, the discordances between them are not well established. Findings MRI and PSMA-PET/CT were discordant in about half of the patients. Most prostate lesions seen on only one modality were significant cancer. Clinical relevance MRI and PSMA-PET/CT are often discordant for assessing the primary prostate tumor. Using both modalities for primary prostate tumor evaluation can provide complementary information that may substantially impact treatment planning.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer. Expression of the lncRNA BOLA3-DT was analyzed between normal and tumor samples in the GDC TCGA PRAD (Genomic Data Commons: The Cancer Genome Atlas Prostate Adenocarcinoma Collection) dataset. Disease progression-related clinicopathological parameters such as serum PSA level (ng/ml) and Gleason score were associated with the expression of BOLA3-DT using the same GDC TCGA PRAD dataset. To validate these findings, the expression of BOLA3-DT was checked in our sample set of 15 PCa (prostate cancer) and 15 BPH (benign hypertrophy of the prostate) patients. In the GDC TCGA PRAD dataset, the expression of the lncRNA BOLA3-DT was significantly downregulated in prostate cancer tissue samples (n = 492) compared to adjacent normal (n = 52; p < 0.0001), and, there was a significant negative correlation between the expression of the lncRNA BOLA3-DT and the serum PSA level (p < 0.01). However, no significant association was found between the lncRNA BOLA3-DT expression and the Gleason score (p > 0.05). In this study, it was found that BOLA3-DT was downregulated in PCa tissue samples compared to BPH samples (p > 0.05). In the GDC TCGA PRAD dataset, it was revealed that BOLA3-DT could serve as an excellent diagnostic marker with a sensitivity of 86.9% and a specificity of 84.6% (AUC-0.916). LncRNA BOLA3-DT, a novel long non-coding RNA, was found to be downregulated in prostate cancer. The expression of the lncRNA BOLA3-DT can serve as a diagnostic marker in prostate cancer.

Baseline PSMA PET/CT parameters predict overall survival and treatment response in metastatic castration-resistant prostate cancer patients.

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying survival outcomes. This study investigated whether baseline PSMA PET/CT parameters are associated with survival and treatment response. Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT before treatment with androgen receptor-targeted agents (ARTAs) or chemotherapy. Intensity-based parameters, volumetric parameters, metastatic sites and DmaxVox (distance between the two outermost voxels) from baseline PSMA PET/CT were collected, as well as age, Gleason score and laboratory parameters. Cox regression analysis evaluated their prognostic value for overall survival (OS). Additionally, a preliminary lesion-level analysis was done (n = 241 lesions) with lesion location and twelve radiomic features selected from previous literature. Logistic regression evaluated their association with PSMA PET/CT-based lesion progression after 3-4 months of treatment. Total tumour volume (PSMA-TV) (HR = 1.41 per doubling [1.17-1.70]), total lesion uptake (TL-PSMA) (HR = 1.40 per doubling [1.16-1.69]) and DmaxVox (HR = 1.31 per 10 cm increase [1.07-1.62]) were prognostic for OS, each independent of baseline PSA level (HR = 0.82 per doubling [0.68-0.98]), haemoglobin level (HR = 0.68 per mmol/L increase [0.49-0.95]) and line of treatment. On lesion-level, location (prostate vs bone OR = 0.23 [0.06-0.83]) and SUVmean (OR = 1.72 per doubling [1.08-2.75]) were independent prognostic markers for lesion progression, morphological and texture-based radiomic features were not. Baseline PSMA PET/CT scans have prognostic value in mCRPC patients and can potentially aid in treatment decision-making. DmaxVox can serve as a simpler alternative to PSMA-TV when automated segmentation software is not available. When combined with PSMA-TV, lower PSA levels indicated worse OS, which may be a marker of tumour dedifferentiation. Further research is needed to validate these models in larger patient cohorts. Question mCRPC is a highly heterogeneous disease, requiring good prognostic markers. Findings PSMA-TV was the best independent prognostic marker for OS; maximum distance between lesions (DmaxVox) can be used as a simpler alternative. Clinical relevance Baseline PSMA PET/CT parameters representing tumour burden were independently associated with OS in mCRPC patients, providing prognosticinsights for clinical decision-making. Although PSMA-TV was the best prognostic marker, DmaxVox can serve as an easier to obtain alternative.

Exploring the Effects of Opioid-Related Drugs on the Clinical Outcome of Prostate Cancer Patients Via Integrated Bioinformatics Analysis.

Opioids are the primary regimens for perioperative analgesia with controversial effects on oncological survival. The underlying mechanism remains unexplored. This study developed survival-related gene co-expression networks based on RNA-seq and clinical characteristics from TCGA cohort. Two survival-related networks were identified, and drug-induced transcriptional profiles were predicted. Immune cell infiltration algorithm, least absolute shrinkage and selection operator (LASSO) regression, and cox proportional models were executed to explore the correlation between opioid-related drugs and prostate cancer patient prognosis. The opioid receptor agonists, represented by tramadol, were evidenced for anti-survival effects on prostate cancer by facilitating the DNA replication and cell cycle, and immune cell infiltration. Conversely, opioid receptor antagonists showed pro-survival effects. A novel prognostic model containing CNIH2, MCCC1, and Gleason scores was established and validated in two independent cohorts. This study revealed opioids' effect on prostate cancer progression, and provided a novel model to predict these regulations in clinical outcomes.

Prognostic value of intraductal carcinoma subtypes and postoperative radiotherapy for localized prostate cancer

BackgroundIntraductal carcinoma of the prostate cancer (IDC-P), as a specific pathological type in prostate cancer which usually implies a poor prognosis. IDC-P morphology can be divided into two subtypes: Pattern 1, sieve like or loose cribriform structures; Pattern 2, solid or dense cribriform structures. The purpose of the study is to identify the impact of IDC-P and its subtypes on the prognosis of patients undergoing post-operative radiotherapy (PORT) after radical prostatectomy (RP) due to localized prostate cancer(PCa).MethodsWe performed a retrospective study of patients with localized PCa treated by RP followed by PORT or not. Patients with localized PCa who underwent RP from August 2013 to December 2020 were included in this study. Inclusion criteria: post-operative PSA dropped to less than 0.1 ng/ml after RP, had at least 1 poor prognostic risk factor (including high Gleason’s grouping; positive surgical margins; seminal vesicle invasion; extraprostatic extension; and lympho-vascular invasion), and were eligible for adjuvant radiotherapy.; In this study, patients who underwent salvage radiotherapy after RP due to biochemical recurrence (two consecutive PSA > 0.2 ng/ml) were also included, but not patients with persistent postoperative PSA > 0.1 ng/ml. Exclusion criteria: patients using other types of therapy prior to biochemical recurrence. Screening cases with pathological results of intraductal carcinoma, subtyping was completed by a pathologist, grouped by intraductal carcinoma (+/-; pattern 1/ 2) and treatment regimen (RP + PORT / RP only), Kaplan-Meier curves were plotted based on the time to biochemical recurrence-free and overall survival of the patients, and Cox regression analyses were performed. Finally, based on the results of Cox regression analysis, we initially predicted the probability of biochemical recurrence and death of the patients by plotting the nomogram.ResultsA total of 139 patients were included in this study with a median follow-up of 61.5 months. K-M curves showed that patients with “IDC-P (+) RP only” had the worst prognosis; patients with IDC-P could have a survival benefit after receiving PORT; whereas patients with non-intraductal carcinoma had a better prognosis than the above patients with or without PORT. In addition, patients with IDC-P(+) pattern 2 were more likely to experience biochemical recurrence and death. Multivariate Cox regression analysis showed that pattern 2 was a risk factor for biochemical recurrence and death. Other BCR-related risk factors in the research: Gleason grading group 5 (HR = 3.343, 95% CI: 1.616–6.916, P = 0.001), PM (HR = 2.124, 95% CI: 1.044–4.320,P = 0.038) and PORT (HR = 0.266, 95%CI: 0.109–0.647, P = 0.004). Other OS-related risk factors in the research: Grading group 5 (HR = 3.642, 95%CI:1.475–8.991, P = 0.005), SVI (HR = 2.522, 95% CI: 1.118–5.691, P = 0.026) and PORT (HR = 0.319, 95%CI: 0.107–0.949, P = 0.040).ConclusionPatients suffering from localized prostate cancer with IDC-P(+), especially IDC-P pattern 2, are more susceptible to biochemical recurrence and death after radical prostatectomy. While postoperative radiotherapy can alleviate the negative prognostic impact from IDC-P. It is implied that IDC-P can also be an indicator to be considered in PORT decision making to some extent.

DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients (n = 41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls (n = 14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castration-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease. Blood samples and clinicopathological data from PCa cases (n = 71) and controls (n = 25) were evaluated. PCa cases were stratified into mCRPCa (n = 16), aggressive (n = 31), and indolent (n = 24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason score (GS) was GS6 (n = 7), GS7 (n = 23), GS ≥ 8 (n = 20), and mCRPCa patients (n = 16). Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% (p < 0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan-Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients. This study evaluated DRC levels through the NER pathway for the first time in 16 Puerto Rican H/L men with mCRPCa. Significant differences in DRC values were found between the controls and the three PCa patient groups. Kaplan-Meier curves revealed that survival probability decreased by approximately 50% by 30 months, and only 20% of the cohort was alive at 50 months, confirming the lethality of mCRPCa in this H/L population. This pilot study represents the first report of metastatic PCa in Puerto Rican men at a global level of DRC levels of mCRPCa patients using a blood-based phenotypic assay.

Physical Color Calibration of Digital Pathology Scanners for Robust Artificial Intelligence Assisted Cancer Diagnosis.

The potential of artificial intelligence (AI) in digital pathology is limited by technical inconsistencies in the production of whole slide images (WSIs). This causes degraded AI performance and poses a challenge for widespread clinical application, as fine-tuning algorithms for each site is impractical. Changes in the imaging workflow can also compromise diagnostic accuracy and patient safety. Physical color calibration of scanners, relying on a biomaterial-based calibrant slide and a spectrophotometric reference measurement, has been proposed for standardizing WSI appearance, but its impact on AI performance has not been investigated. We evaluated whether physical color calibration can enable robust AI performance. We trained fully supervised and foundation model based AI systems for detecting and Gleason grading prostate cancer using WSIs of prostate biopsies from the STHLM3 clinical trial (n=3,651) and evaluated their performance in three external cohorts (n=1,161) with and without calibration. With physical color calibration, the fully supervised system's concordance with pathologists' grading (Cohen's linearly weighted kappa) improved from 0.439 to 0.619 in the Stavanger University Hospital cohort (n=860), from 0.354 to 0.738 in the Karolinska University Hospital cohort (n=229), and from 0.423 to 0.452 in the Aarhus University Hospital cohort (n=72). The foundation model's concordance improved from 0.739 to 0.760 (Karolinska), from 0.424 to 0.459 (Aarhus) and from 0.547 to 0.670 (Stavanger). The study demonstrates that physical color calibration provides a potential solution to the variation introduced by different scanners, making AI-based cancer diagnostics more reliable and applicable in diverse clinical settings.

Screening for Predictive Factors of Efficacy of Second-Generation Androgen Receptor Axis-Targeted Agents in Patients With High-Risk Metastatic Hormone-Sensitive Prostate Cancer.

Differences in the effectiveness of second-generation androgen receptor axis-targeted agents (ARATs) in high-risk metastatic hormone-sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high-risk mHSPC and compare their long-term effectiveness. Four hundred and sixty-six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients. Univariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high-risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA-PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high-risk mHSPC with Gleason pattern 5 treated with ARATs. Gleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high-risk mHSPCs.

Development of Novel Nomograms to Predict 5- and 7-Year Biochemical-Recurrence-Free Survival in High-Risk Prostate Cancer Patients After Carbon-Ion Radiotherapy and Androgen Deprivation Therapy

Background: The aim of this study was to develop nomograms predicting 5- and 7-year biochemical-recurrence (BCR)-free survival in high-risk prostate cancer (PCa) patients treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). Methods: We retrospectively evaluated 785 high-risk PCa patients treated with CIRT and ADT. Based on the least absolute shrinkage and selection operator model, two nomograms predicting 5- and 7-year BCR-free survival were developed and internally validated. The ability of each nomogram to predict BCR-free survival was determined by calculating the area under the survival curve (AUC). Results: The 5- and 7-year BCR-free survival rates were 92.1% and 89.3%, respectively. Age, prostate-specific antigen level, clinical T stage, and Gleason score were incorporated into the nomogram predicting 5-year BCR-free survival. In addition to these variables, the percentage of positive biopsy cores was also added to the nomogram predicting 7-year BCR-free survival. The AUC value of each nomogram showed suboptimal-to-good discrimination. Conclusions: We developed the first nomograms accurately predicting BCR-free survival in high-risk PCa patients treated with CIRT and ADT. These nomograms will enable adequate understanding and explanation of BCR-free survival to patients when clinicians use them.

Development and validation of nomograms for predicting pentafecta outcomes before and after robot-assisted radical prostatectomy: a retrospective study

Prostate cancer (PCa) is one of the most common cancers among men worldwide, and robot-assisted radical prostatectomy (RARP) is a widely used treatment for localized PCa. Achieving pentafecta outcomes, which include continence, potency, cancer control, free surgical margins, and no major complications, is a critical measure of surgical success and long-term prognosis. However, predicting these outcomes remains challenging. In this retrospective, single-center study, we analyzed data from 1,752 patients who underwent RARP for localized prostate adenocarcinoma between August 2009 and April 2023. The pentafecta outcome was achieved in 290 patients (16.6%). Multivariate analysis revealed that bilateral nerve sparing significantly increased the likelihood of achieving the pentafecta outcome (odds ratio 10.36, 95% CI: 5.75–18.66; p < 0.001). Preoperative potency and bilateral nerve sparing were also identified as key predictors. Nomograms were developed using preoperative and postoperative variables, including age, PSA level, biopsy Gleason score, clinical stage, pathological tumor stage, tumor grade, nerve sparing, and preoperative potency. Internal validation of the nomograms was performed using bootstrapping methods, demonstrating robust predictive performance. These nomograms provide valuable tools for personalized surgical planning and patient counseling and may be applicable to broader populations, given the inclusion of universally recognized predictive factors and rigorous validation. This study presents the development and validation of nomograms to predict pentafecta outcomes before and after RARP. These nomograms provide valuable tools for clinicians to estimate the likelihood of achieving postoperative pentafecta outcomes. Incorporating these nomograms into clinical practice may improve patient counseling and shared decision-making.

Impact of ISUP grade group on cancer-specific mortality in radical prostatectomy-treated prostate cancer patients with organ-confined disease

Introduction: We aimed to test the impact of International Society of Urological Pathology (ISUP) grade group (GG) on cancer-specific mortality (CSM) in organ-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP). Methods: RP organ-confined prostate cancer (PCa) patients were identified (Surveillance, Epidemiology, and End Results 2004−2015). Cancer-specific survival (CSS) rates were tested in Kaplan-Meier plots and multivariable Cox regression (MCR) models according to GG: 1–3 vs. 4 vs. 5. Sensitivity analyses addressed GG4 and GG5 patients with available primary and secondary Gleason score (GS). Results: Overall, 61 172 patients with RP organ-confined PCa were identified. Of these, 57 715 (94.4%), 2036 (3.3%) and 1421 (2.3%) harbored GG1–3, 4, and 5, respectively. In Kaplan-Meier analyses, seven-years’ CSS estimates were 99.6 vs. 98.2 vs. 93.8% for GG1–3 vs. 4 vs. 5, respectively (p&lt;0.001). In MCR models, GG4 (hazard ratio [HR] 2.72, p&lt;0.001) and 5 (HR 9.95, p&lt;0.001) independently predicted higher CSM, relative to GG1–3. Furthermore, GG5 also independently predicted higher CSM (HR 3.72, p&lt;0.001) vs. GG4. In sensitivity analyses, 1.2, 1.6, and 2.4 CSM events per 1000 person-years of followup were respectively recorded for GS 4+4, 3+5, and 5+3 patients. Conversely, 4.8 vs. 5.3 CSM events per 1000 person-years of followup were respectively recorded for GS 4+5 vs. 5+4/5+5 patients. Conclusions: In organ-confined PCa, at RP, a small proportion of patients harbor GG4–5. These patients exhibit higher CSM than their GG1–3 counterparts. Moreover, detectable mortality rate differences indicate a dose-response effect according to primary and secondary GS. This phenomenon applies in both GG4 and GG5, as well as between GG4 and GG5.

UBE2S, downregulated by miR-152-3p, facilitates prostate cancer progression through the PTEN-mediated AKT/mTOR pathway.

In recent years, the incidence and mortality rates of prostate cancer (PCa) have still not been significantly reduced and the mechanisms of tumor onset and progression are still not fully understood. The pathogenic mechanisms and upstream regulation of UBE2S expression in prostate cancer have not been elucidated. Here, we performed bioinformatic analysis of public databases to reveal the expression of UBE2S in PCa and its association with Gleason score, tumor staging, biochemical recurrence, and survival. Subsequently, the effect of UBE2S on the proliferation and invasive capacity of PCa cells was explored. Next, miR-152-3p was identified to bind to the 3'-UTR of UBE2S mRNA and down-regulated in PCa through luciferase reporter assays. Dual immunofluorescence assay and co-immunoprecipitation assays were performed to verify the regulatory role of UBE2S on PTEN. Finally, the molecular mechanism of UBE2S regulation of PCa progression was further confirmed by rescue experiments and in vivo nude mouse subcutaneous transplantation tumor experiments. UBE2S expression was upregulated in PCa and correlated with patient Gleason score, TNM stage, biochemical recurrence, and disease-free survival. miR-152-3p regulated UBE2S expression in PCa by binding to the UBE2S mRNA 3'-UTR. Mechanistically, UBE2S combines with PTEN and ubiquitinates it, leading to PTEN degradation and ultimately promoting PCa progression via the AKT/mTOR signaling pathway. UBE2S, down-regulated by miR-152-3p, plays an important role in the onset and progression of PCa through the PTEN-mediated Akt/mTOR pathway and may become a new diagnostic marker and therapeutic target for PCa.

Prognostic significance of the mEPE score in intermediate-risk prostate cancer patients undergoing ultrahypofractionated robotic SBRT.

This study aimed to evaluate the prognostic significance of magnetic resonance imaging (MRI) parameters on biochemical failure-free survival (BFS) in patients diagnosed with intermediate-risk prostate cancer and treated with robotic ultrahypofractionated stereotactic body radiotherapy (SBRT) without androgen deprivation therapy (ADT). Aretrospective analysis was conducted in patients with intermediate-risk prostate cancer undergoing robotic SBRT delivered in five fractions with atotal radiation dose of 35-36.25 Gy. The primary endpoint was biochemical failure as defined by the Phoenix criteria. Among other clinicopathological data, Tstage, Prostate Imaging-Reporting and Data System (PI-RADS) score, and multiparametric magnetic resonance imaging-based extra-prostatic extension (mEPE) score were collected and analyzed using the log-rank test. Atotal of 74patients were eligible for analysis. Median age at treatment was 68.8 years and median prostate volume was 47.8cm3. Fifty-four and 14patients were diagnosed with Gleason scores 7a and 7b, respectively. In total, 40patients were classified as having unfavorable intermediate-risk prostate cancer according to American Urological Association/American Society for Radiation Oncology/ Society of Urologic Oncology (AUA/ASTRO/SUO) guidelines. The median follow-up was 30months (range: 4-91.2 months; interquartile range (IQR): 18.5-48months). The 3‑year BFS was 92%. Atotal of 12(16.2%) biochemical failures were reported. In univariate analysis, an mEPE score of 5, the delivered total radiation dose (35 Gy vs. 36.25 Gy), and aprostate-specific antigen (PSA) nadir >1 ng/ml were associated with lower BFS (mEPE-BFS: p < 0.001, total radiation dose-BFS: p = 0.04, PSAnadir-BFS: p =< 0.001). Patients diagnosed with intermediate-risk prostate cancer with ahigh mEPE score are more likely to experience biochemical failure after SBRT. Treatment intensification measures, such as administration of concomitant ADT, should be considered.

Prognostic Testing for Prostate Cancer-A Cost-Effectiveness Analysis Comparing a Prostatype P-Score Biomarker Approach to Standard Clinical Practice.

The Prostatype score (P-score) is a prognostic biomarker that integrates a three-gene (IGFBP3, F3, and VGLL3) signature derived from prostate biopsy samples, with key clinical parameters, including prostate-specific antigen (PSA) levels, Gleason grade, and tumor stage at diagnosis. The test has demonstrated superior predictive accuracy for prostate cancer outcomes compared with traditional risk categorization systems such as D'Amico. Notably, it reclassifies a higher proportion of patients into the low-risk category, making them eligible for active surveillance. This study assessed the cost-effectiveness of the P-score in comparison with D'Amico and the Swedish National Prostate Cancer Register (NPCR) risk categorization systems. A two-step decision analytic model was developed. The model consisted of a decision tree-informed Markov structure estimating the lifetime outcomes of 60-year-old men with diagnosed prostate cancer. Prostate cancer was classified as low-risk, intermediate-risk, or high-risk using either the P-score or D'Amico. Initial therapy was based on observed treatment patterns from the Swedish NPCR. Costs (SEK, year 2022) and quality-adjusted life years (QALYs) were estimated from a healthcare perspective and discounted at 3% per year; incremental cost-effectiveness ratio (ICER) was the primary outcome. The P-score led to cost savings and generated an additional 0.19 QALYs compared with D'Amico. The added costs of the genetic test and higher costs of active surveillance and radiotherapy were counterbalanced by savings from reduced costs of surgery, treatment-related side-effects, and metastatic disease. The gain in QALYs was primarily due to the avoidance of metastatic disease and a reduction in treatment-related side-effects. The results of this study suggest that the P-score is likely to be a cost-effective alternative to D'Amico for prognostic evaluation of newly diagnosed prostate cancer in Sweden and compared with NPCR when health-related quality of life was included.

Early Versus Delayed Androgen Deprivation Therapy for Biochemical Recurrence After Local Curative Treatment in Non-Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of the Literature.

The ideal timing of androgen deprivation therapy (ADT) for patients with biochemical recurrence (BCR) of prostate cancer (PCa) remains controversial due to its side effects and uncertain impact on survival outcomes. We performed a review of the current literature by comprehensively searching the PubMed, Embase, and Cochrane databases to determine the optimal timing of ADT initiation after biochemical recurrence. We selected 26 studies including systematic reviews, randomized controlled trials (RCTs), and retrospective studies, while also reviewing practice guidelines. Not all patients with BCR cancer experience clinical or radiological progression. While early ADT may delay progression, evidence of its effect on PCa-specific mortality remains inconclusive. The PSA thresholds for initiating ADT vary, complicating decision-making. Key predictors of progression include a short PSA doubling time (PSADT), a high Gleason score (GS), and a brief interval to BCR of PCa post-radiotherapy (RT). Combining ADT with androgen receptor pathway inhibitors (ARPIs) has been shown to improve metastasis-free survival in high-risk patients. The ideal timing of ADT initiation in BCR PCa remains uncertain. Early ADT can help control the progression, but its effect on PCa-specific mortality is unclear. Stratifying patients by their risk factors, such as their PSADT, GS, and time to BCR can guide individualized treatment. In high-risk patients, delaying ADT should be avoided, while combining ADT with an androgen receptor pathway inhibitor (ARPI) may further improve outcomes.

Haralick Texture Analysis for Differentiating Suspicious Prostate Lesions from Normal Tissue in Low-Field MRI.

This study evaluates the feasibility of using Haralick texture analysis on low-field, T2-weighted MRI images for detecting prostate cancer, extending current research from high-field MRI to the more accessible and cost-effective low-field MRI. A total of twenty-one patients with biopsy-proven prostate cancer (Gleason score 4+3 or higher) were included. Before transperineal biopsy guided by low-field (58-74mT) MRI, a radiologist annotated suspicious regions of interest (ROIs) on high-field (3T) MRI. Rigid image registration was performed to align corresponding regions on both high- and low-field images, ensuring an accurate propagation of annotations to the co-registered low-field images for texture feature calculations. For each cancerous ROI, a matching ROI of identical size was drawn in a non-suspicious region presumed to be normal tissue. Four Haralick texture features (Energy, Correlation, Contrast, and Homogeneity) were extracted and compared between cancerous and non-suspicious ROIs. Two extraction methods were used: the direct computation of texture measures within the ROIs and a sliding window technique generating texture maps across the prostate from which average values were derived. The results demonstrated statistically significant differences in texture features between cancerous and non-suspicious regions. Specifically, Energy and Homogeneity were elevated (p-values: <0.00001-0.004), while Contrast and Correlation were reduced (p-values: <0.00001-0.03) in cancerous ROIs. These findings suggest that Haralick texture features are both feasible and informative for differentiating abnormalities, offering promise in assisting prostate cancer detection on low-field MRI.

Ultrasound radiomics model based on grayscale transrectal ultrasound-guided biopsy for diagnosing prostate cancer and predicting distant metastasis.

A prostate ultrasound (US) imaging omics model was established to assess its effectiveness in diagnosing prostate cancer (PCa), predicting Gleason score (GS), and determining the likelihood of distant metastasis. US images of patients with prostate pathology confirmed by biopsy or surgery at our hospital were retrospectively analyzed. Regions of interest (ROI) segmentation, feature extraction, feature screening, and the construction and training of the radiomics model were performed. Area under the curve (AUC) for the magnetic resonance imaging Prostate Imaging Reporting and Data System (MRI PI-RADS) classification, radiomics alone, and radiomics combined with prostate-specific antigen (PSA) in diagnosing PCa were 70.74%, 71.13%, and 90.47%, respectively. AUCs for the MRI PI-RADS classification, radiomics alone, and radiomics combined with PSA in predicting the GS of PCa were 75.6%, 74.7%, and 88.9%, respectively. Furthermore, AUCs for MRI PI-RADS classification and radiomics alone in predicting distant metastasis of PCa were 66.7% and 90.8%, respectively. The combination of ultrasonic imaging omics and serum PSA significantly improves the efficiency of PCa diagnosis, GS prediction, and distant metastasis prediction. This method is an important tool for PCa screening and follow-up.

DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.

Prostate cancer is a common cancer with a variable prognosis. Its management is currently guided by histological and biological markers such as the Gleason score and PSA. Developments in molecular biology are now making it possible to identify new targets for better classification of prostate cancer. Among emerging biomarker, DNA methylation, an epigenetic process, is increasingly being studied in carcinogenesis. Techniques for analyzing DNA methylation are constantly improving, and digital PCR now allows absolute methylation quantification with high sensitivity. These techniques can be performed on circulating tumor DNA. We conducted a literature review of scientific articles addressing the topic of DNA methylation in prostate cancer. This review summarizes the different genes whose methylation is involved in carcinogenesis and their clinical implications, both diagnostic and prognostic. Methylation monitoring could also be useful for the prediction of treatment response. However, most studies are retrospective, and prospective studies are needed to validate these data.