International Society of Urological Pathology (ISUP) Gleason Grade Groups stratify outcomes in the CHHiP Phase 3 prostate radiotherapy trial.

OBJECTIVES: To compare the results of Gleason Grade Group (GGG) classification following central pathology review with previous local pathology assessment, and to examine the difference between using overall and worst GGG in a large patient cohort treated with radiotherapy and short-course hormone therapy. PATIENTS AND METHODS: Patients with low- to high-risk localized prostate cancer were randomized into the multicentre CHHiP fractionation trial between 2002 and 2011. Patients received short-course hormone therapy (≤6 month) and radical intensity-modulated radiotherapy (IMRT). Of 2749 consented patients, 1875 had adequate diagnostic biopsy tissue for blinded central pathology review. The median follow-up was 9.3 years. Agreement between local pathology and central pathology-derived GGG and between central pathology-derived overall and worst GGG was assessed using kappa (κ) statistics. Multivariate Cox regression and Kaplan-Meier methods were used to compare the biochemical/clinical failure (BCF) and distant metastases (DM) outcomes of patients with GGG 1-5. RESULTS: There was poor agreement between local pathology- and central pathology-derived GGG (κ = 0.19) but good agreement between overall and worst GGG on central pathology review (κ = 0.89). Central pathology-derived GGG stratified BCF and DM outcomes better than local pathology, while overall and worst GGG on central pathology review performed similarly. GGG 3 segregated with GGG 4 for BCF, with BCF-free rates of 90%, 82%, 74%, 71% and 58% for GGGs 1-5, respectively, at 8 years when assessed using overall GGG. There was a progressive decrease in DM-free rates from 98%, 96%, 92%, 88% and 83% for GGGs 1-5, respectively, at 8 years with overall GGG. Patients (n = 57) who were upgraded from GGG 2-3 using worst GS had BCF-free and DM-free rates of 74% and 92% at 8 years. CHHiP eligibility criteria limit the interpretation of these results. CONCLUSION: Contemporary review of International Society of Urological Pathology GGG successfully stratified patients treated with short-course hormone therapy and IMRT with regard to both BCF-free and DM-free outcomes. Patients upgraded from GGG 2 to GGG 3 using worst biopsy GS segregate with GGG 3 on long-term follow-up. We recommend that both overall and worst GS be used to derive GGG.

Interaction of patient age and high-grade prostate cancer on targeted biopsies of MRI suspicious lesions.

OBJECTIVES: To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS: From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS: A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION: In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.

The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy.

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

Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) Staging Manual has been updated and improved to ensure the highest degree of clinical relevance and to improve its utility for patient evaluation and clinical research. Major changes include: 1) pathologically organ-confined disease is now considered pT2 and is no longer subclassified by extent of involvement or laterality, 2) tumor grading now includes both the Gleason score (as in the seventh edition criteria) and the grade group (introduced in the eighth edition criteria), 3) prognostic stage group III includes select, organ-confined disease based on prostate-specific antigen and Gleason/grade group status, and 4) 2 statistical prediction models are included in the staging manual. The AJCC will continue to critically analyze emerging prostate cancer biomarkers and tools for their ability to prognosticate and guide treatment decision making with the highest level of accuracy and confidence for patients and physicians. CA Cancer J Clin 2017;67:245-253. © 2017 American Cancer Society.

CRISPR screening reveals gleason score and castration resistance related oncodriver ring finger protein 19 A (RNF19A) in prostate cancer.

Prostate cancer (PCa) is one of the most lethal causes of cancer-related death in male. It is characterized by chromosomal instability and disturbed signaling transduction. E3 ubiquitin ligases are well-recognized as mediators leading to genomic alterations and malignant phenotypes. There is a lack of systematic study on novel oncodrivers with genomic and clinical significance in PCa. In this study we used clustered regularly interspaced short palindromic repeats (CRISPR) system to screen 656 E3 ubiquitin ligases as oncodrivers or tumor repressors in PCa cells. We identified 51 significantly changed genes, and conducted genomic and clinical analysis on these genes. It was found that the Ring Finger Protein 19 A (RNF19A) was a novel oncodriver in PCa. RNF19A was frequently amplified and highly expressed in PCa and other cancer types. Clinically, higher RNF19A expression correlated with advanced Gleason Score and predicted castration resistance. Mechanistically, transcriptomics, quantitative and ubiquitination proteomic analysis showed that RNF19A ubiquitylated Thyroid Hormone Receptor Interactor 13 (TRIP13) and was transcriptionally activated by androgen receptor (AR) and Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A). This study uncovers the genomic and clinical significance of a oncodriver RNF19A in PCa. The results of this study indicate that targeting AR/HIF1A-RNF19A-TRIP13 signaling axis could be an alternative option for PCa diagnosis and therapy.

Analysis of the Gene Networks and Pathways Correlated with Tissue Differentiation in Prostate Cancer.

Prostate cancer (PCa) is the most prevalent non-cutaneous cancer in men. Early PCa detection has been made possible by the adoption of screening methods based on the serum prostate-specific antigen and Gleason score (GS). The aim of this study was to correlate gene expression with the differentiation level of prostate adenocarcinomas, as indicated by GS. We used data from The Cancer Genome Atlas (TCGA) and included 497 prostate cancer patients, 52 of which also had normal tissue sample sequencing data. Gene ontology analysis revealed that higher GSs were associated with greater responses to DNA damage, telomere lengthening, and cell division. Positive correlation was found with transcription factor activator of the adenovirus gene E2 (E2F) and avian myelocytomatosis viral homolog (MYC) targets, G2M checkpoints, DNA repair, and mitotic spindles. Immune cell deconvolution revealed high M0 macrophage counts and an increase in M2 macrophages dependent on the GS. The molecular pathways most correlated with GSs were cell cycle, RNA transport, and calcium signaling (depleted). A combinatorial approach identified a set of eight genes able to differentiate by k-Nearest Neighbors (kNN) between normal tissues, low-Gleason tissues, and high-Gleason tissues with high accuracy. In conclusion, our study could be a step forward to better understanding the link between gene expression and PCa progression and aggressiveness.

Ribosome-binding protein-1 (RRBP1) expression in prostate carcinomas and its relationship with clinicopathological prognostic factors.

INTRODUCTION: Studies in recent years have shown that ribosome-binding protein-1 (RRBP1) is expressed at high rates in many cancers and that it may be a potential prognostic biomarker. The objective of the present study is to determine the RRBP1 expression level in prostatic carcinoma and neighboring non-neoplastic prostate tissue, the relationship between its expression level with prognostic factors, and the role of RRBP1 in the development of prostate cancer. MATERIALS AND METHODS: The study included 45 patients who were diagnosed with prostatic carcinoma and underwent radical prostatectomy in our center between the years 2010 and 2021. Pathology reports were reviewed. Mann-Whitney U test was used for the comparison of RRBP1 and GADPH values of the cases (control and tumoral tissue) between the primary tumor stage (pT) and Gleason score (GS) groups. Hierarchical regression analysis was used to explain the effective variables in explaining the RRBP1 value of the research cases. RESULTS: According to the Mann-Whitney U test, mean and median RRBP1-T values of the cases with GS ≥ 8 were detected to be statistically significantly higher than the mean and median RRBP1-T values of the cases with GS < 8. CONCLUSION: We found out that RRBP1 was expressed at higher rates in patients with high GS and advanced-stage patients. This result indicated that RRBP1 expression may be important in predicting the prognosis of prostate carcinoma.

Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

BACKGROUND: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: HGPCa are highly infiltrated by exhausted CD8+ T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8+ T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8+  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8+  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8+  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS: Our study reveals a suppressive TME with high levels of CD8+ T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

Cribriform morphology is associated with higher risk of biochemical recurrence after radical prostatectomy in patients with Grade Group 5 prostate cancer.

AIMS: Grade Group 5 (GG5) prostate cancer (PCa) is associated with a high risk of disease recurrence after radical prostatectomy (~75% at 5 years). However, this is a heterogeneous category that includes neoplasms with different combinations of Gleason pattern (GP) 4 and 5. Within GP4, large cribriform growth has been associated with adverse disease-specific outcomes in GG2-4 PCa. Less is known about the significance of cribriform morphology and the different histologic patterns of GP5 in GG5 PCa. METHODS AND RESULTS: In this study we evaluated the prognostic implications of cribriform morphology (either invasive or intraductal, henceforth "cribriform") and large solid growth or comedonecrosis (comedo/solid) in patients with GG5 PCa. One-hundred and thirty prostatectomies from a single institution were analysed. The presence of comedo/solid components was associated with a higher frequency of concurrent cribriform PCa (85.7% versus 45.9%, P < 0.001), lymphovascular invasion (44.6% versus 27%, P = 0.04), and biochemical recurrence (48.2% versus 28.4%, P = 0.03). The presence of large cribriform growth was associated with a higher frequency of extraprostatic involvement (i.e. pT3a-b; 85.3% versus 68.7%, P = 0.02), positive surgical margins (47.6% versus 29.2%, P = 0.04) and biochemical recurrence (47.6% versus. 18.7%, P = 0.001). Kaplan-Meier analysis demonstrated that GG5 PCa with cribriform or comedo/solid components had a higher probability of biochemical recurrence. Multivariable analysis showed that only cribriform components were an independent predictor of a higher risk of biochemical recurrence in this series. CONCLUSION: These findings highlight the importance of reporting the presence of cribriform components in GG5 PCa and suggest that cribriform morphology might help decide postsurgical management in these patients.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

Identification of miR-1-3p, miR-143-3p and miR-145-5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation.

Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143-3p and miR-145-5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143-3p/145-5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with ß-catenin. In all, we suggest that miR-1-3p/143-3p/145-5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with ß-catenin.

Critical Evaluation of Transcripts and Long Noncoding RNA Expression Levels in Prostate Cancer Following Radical Prostatectomy.

INTRODUCTION: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk. METHODS: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status. RESULTS: Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression. CONCLUSION: While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.

A high high-density lipoprotein level is associated with Gleason score upgrade in Chinese patients diagnosed with high-grade prostate carcinoma.

BACKGROUND: The high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU. METHODS: Patients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups. RESULTS: A total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005-1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904-1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998-59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer. CONCLUSIONS: These laboratory examination data could provide urologists with information before making a therapeutic protocol.

A radiomics based method for prediction of prostate cancer Gleason score using enlarged region of interest.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men worldwide, and its timely diagnosis and treatment are becoming increasingly important. MRI is in increasing use to diagnose cancer and to distinguish between non-clinically significant and clinically significant PCa, leading to more precise diagnosis and treatment. The purpose of this study is to present a radiomics-based method for determining the Gleason score (GS) for PCa using tumour heterogeneity on multiparametric MRI (mp-MRI). METHODS: Twenty-six patients with biopsy-proven PCa were included in this study. The quantitative T2 values, apparent diffusion coefficient (ADC) and signal enhancement rates (α) were calculated using multi-echo T2 images, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI), for the annotated region of interests (ROI). After texture feature analysis, ROI range expansion and feature filtering was performed. Then obtained data were put into support vector machine (SVM), K-Nearest Neighbor (KNN) and other classifiers for binary classification. RESULTS: The highest classification accuracy was 73.96% for distinguishing between clinically significant (Gleason 3 + 4 and above) and non-significant cancers (Gleason 3 + 3) and 83.72% for distinguishing between Gleason 3 + 4 from Gleason 4 + 3 and above, which was achieved using initial ROIs drawn by the radiologists. The accuracy improved when using expanded ROIs to 80.67% using SVM and 88.42% using Bayesian classification for distinguishing between clinically significant and non-significant cancers and Gleason 3 + 4 from Gleason 4 + 3 and above, respectively. CONCLUSIONS: Our results indicate the research significance and value of this study for determining the GS for prostate cancer using the expansion of the ROI region.

Predictive Factors for Gleason Score Upgrading in Patients with Prostate Cancer after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP). METHODS: We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied. RESULTS: Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = -0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = -0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable. CONCLUSIONS: Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.

A national questionnaire survey of Japanese urologists on active surveillance for low- and intermediate-risk prostate cancer.

OBJECTIVE: To conduct a national questionnaire survey of Japanese urologists on active surveillance (AS) for low- and intermediate-risk prostate cancer (PCa). METHODS: A questionnaire was sent to 922 Japanese Urological Association Teaching Base Hospitals. The items included were years of experience as a urologist, sex, workplace, treatment equipment owned, specialty area of daily practice, specialty area of urological cancer, and six hypothetical cases of AS. The cases were categorized by the following Gleason scores: 3 + 3 low risk of PCa, 3 + 4 intermediate risk, and 4 + 3 intermediate risk, with or without comorbidities for each case. Comorbidities were defined as cardiovascular diseases or illnesses warranting anticoagulant therapy. RESULTS: Altogether, 1962 questionnaires were analyzed. Responses were almost equally distributed among all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Percentages of proposed AS for low risk/no comorbidity, low risk/with comorbidity, intermediate-risk 3 + 4/no comorbidity, intermediate risk 3 + 4/with comorbidity, intermediate risk 4 + 3/no comorbidity, and intermediate risk 4 + 3/with comorbidity were 90.5%, 90%, 39.5%, 48.7%, 15%, and 22%, respectively. Analysis of the correspondents' backgrounds showed that the more the urologists' years of experience, the less they were to advise AS of low-risk patients. In the presence of comorbidities, urologists across all age groups tended to propose AS, even in the same Gleason grade group. Cancer center urologists recommended AS more often than their counterparts at general and university hospitals. CONCLUSIONS: Approximately 40% of urologists proposed AS for intermediate-risk cases, confirming that AS for intermediate-risk patients is being considered in Japan.

Intravoxel incoherent motion predicts positive surgical margins and Gleason score upgrading after radical prostatectomy for prostate cancer.

BACKGROUND: Whether Intravoxel incoherent motion (IVIM) can be used as a predictive tool of positive surgical margins (PSMs) and Gleason score (GS) upgrading in prostate cancer (PCa) patients after radical prostatectomy (RP) still remains unclear. The aim of this study is to explore the ability of IVIM and clinical characteristics to predict PSMs and GS upgrading. METHODS: A total of 106 PCa patients after RP who underwent pelvic mpMRI (multiparametric Magnetic Resonance Imaging) between January 2016 and December 2021 and met the requirements were retrospectively included in our study. IVIM parameters were obtained using GE Functool post-processing software. Logistic regression models were fitted to confirm the predictive risk factor of PSMs and GS upgrading. The area under the curve and fourfold contingency table were used to evaluate the diagnostic efficacy of IVIM and clinical parameters. RESULTS: Multivariate logistic regression analyses revealed that percent of positive cores, apparent diffusion coefficient and molecular diffusion coefficient (D) were independent predictors of PSMs (Odds Ratio (OR) were 6.07, 3.62 and 3.16, respectively), Biopsy GS and pseudodiffusion coefficient (D*) were independent predictors of GS upgrading (OR were 0.563 and 7.15, respectively). The fourfold contingency table suggested that combined diagnosis increased the ability of predicting PSMs but had no advantage in predicting GS upgrading except the sensitivity from 57.14 to 91.43%. CONCLUSIONS: IVIM showed good performance in predicting PSMs and GS upgrading. Combining IVIM and clinical factors enhanced the performance of predicting PSMs, which may contribute to clinical diagnosis and treatment.

Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review.

Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The TMPRSS2:ERG fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.

[Difference between prostate cancer patients' Gleason scores from preoperative biopsy and those from postoperative pathology].

OBJECTIVE: To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology, identify the possible factors influencing results of scoring, and construct a risk scoring model. METHODS: We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis. Using paired sample t-test, we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology, analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores, and calculated and visualized the relative risk values of the factors through Poisson regression. From the continuous variables with statistical significance, we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis, established a risk scoring model, generated risk coefficients, and evaluated the predictive ability of the model using the ROC curve. Based on the results of imaging examination with statistically significant differences, we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves, decision curves and ROC curves. RESULTS: The results of paired sample t-test for 210 PCa patients showed statistically significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology (P < 0.001). There were significant differences in the body weight, BMI and PSA level as well as in all other factors but prostate calcification between the patients with consistent and those with inconsistent Gleason scores (all P < 0.05). An 8-factor prediction model was successfully constructed, which could predict the consistency of Gleason scores, with a better predicting performance than the single indicator within the model. The nomogram exhibited a C-index value of 0.85, with the calibration curve similar to the standard one, the threshold of the decision curve 0.10－0.92, and the area under the ROC curve higher than other predictive indicators. CONCLUSION: Based on the demographic and clinical data on PCa patients, a risk prediction model and a column chart were successfully constructed, which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

Impact of prostate biopsy secondary pathology review on radiotherapy management.

BACKGROUND: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution. METHODS: We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen's kappa statistic and agreement of treatment options was determined by McNemar's exact tests. RESULTS: GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ2 = 5.33, p = 0.0386; χ2 = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895). CONCLUSIONS: We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.