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Purpose To evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients. Methods Patients with PCa, who underwent [68 Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1–3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student’s t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS). Results All radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS. Conclusion All single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics.

Purpose: To analyze the difference in the prediction accuracy with an active surveillance (AS) protocol between two eras (pre-International Society of Urological Pathology [pre-ISUP]-2014 vs. post-ISUP2014). Materials and Methods:Materials and Methods: We retrospectively analyzed 118 candidates for AS who underwent radical prostatectomy between 2009 and 2017. We divided our patients into two groups (group 1 [n=57], operation date 2009–2015; group 2 [n=61], op-eration date 2016–2017). Pathologic slides in group 1 were reviewed to distinguish men with cribriform pattern (CP) because the determination of Gleason scores in old era had been based on pre-ISUP2014 classification. Postoperative outcomes in the two eras were analyzed twice: first, all men in group 1 vs. group 2; second, the remaining men after excluding those with CPs in group 1 vs. group 2. Results:Results: The proportion of men with insignificant prostate cancer (iPCa) was significantly lower in group 1 than in group 2 (36.8% vs. 57.4%, p=0.040). After excluding 11 men with CPs from group 1, those remaining (46 men) were compared again with group 2. In this analysis, the proportion of men with iPCa was similar between the two groups (old vs. contempo-rary era: 41.3% vs. 57.4%, p=0.146). Nine of 11 men with CP had violated the criteria for iPCa in the earlier comparison. Conclusions:Conclusions: The accuracy of the AS protocol has been affected by the coexistence of CPs and pure Gleason 6 tumors in the pre-ISUP2014 era. We suggest to use only contemporary (post-ISUP2014) data to analyze the accuracy with AS protocols in future studies.

Introduction: Prostate cancer (PCa) is the commonest maliganacy among men of African descent. The possible role of trace elements like Zinc in its aetiogenesis and disease severity remains controversial. This paper aims to identify the relationship between tissue zinc concentration and the occurrence of prostate cancer. And to identify the relationship between the tissue zinc concentration and the disease severity (using the prostate specific antigen (PSA) and Gleason scores (GS)).Methodology: A cross-sectional study of 41 consecutive consenting men with histologically confirmed PCa and 41 age-matched controls. Toe-nail clippings were obtained from both groups and assayed for zinc using the Particle induced X-ray emission (PIXE) technique. Zinc concentrations were compared between cases and controls. A correlation analysis was performed to determine relationship between Zinc concentration and disease severity (PSA and GS). Results: Forty one men each were recruited in the Prostate cancer and control groups for this study. PCa group had a mean age of 72.83 ± 7.06 years while the control group was 70.73 ±6.40 years. There was statistically significant higher toe-nail Zn concentration among Prostate cancer patients than controls (P= 0.028, t=2.28, df=40). The mean PSA values among the Prostate cancer group was 46.10 ± 40.62ng/ml and mode GS was 8.There was neither a correlation between toe-nail Zn concentration and serum PSA levels (p=0.386) nor with the GS. Conclusion: This study found a statistically significant higher toe-nail Zn concentration among men with PCa compared with age-matched controls. There was however no correlation between toe-nail Zn concentration and the serum prostate specific antigen or Gleason score.

Background The early detection of bone metastases is very important in prostate cancer follow-up. This study aimed to compare conventional tumor markers, namely free prostate-specific antigen (free PSA), total prostate-specific antigen (total PSA), free PSA/total PSA ratio, alkaline phosphatase (ALP) values, Gleason scores and 99 m Tc-MDP bone scintigraphy findings in the prediction of bone metastases in prostate cancer. Methods In total, 175 patients with prostate cancer who underwent whole-body bone scintigraphy were included in the study. All selected scintigraphic studies were reprocessed. Free PSA, total PSA, free PSA/total PSA ratio, alkaline phosphatase (ALP) values and Gleason scores of patients were recorded. Results The results of our study show that the presence of bone metastasis correlates very weakly with free PSA/total PSA ratio (rho = 0.179), weakly with total PSA (rho = 0.318) and Gleason score (rho = 0.382), moderately with ALP (rho = 0.539), free PSA (0.416). Only ALP variable had a diagnostic value and ALP cutoff value was 76.50 IU/L, with 80% sensitivity and 82.1% specificity. Conclusion According to the results of our study; the free PSA, total PSA, free PSA/total PSA ratio and Gleason score values were not considered as a reliable parameter in the prostate cancer cases follow-up for bone metastasis development. Only ALP had a diagnostic value and ALP cutoff value was 76.50 IU / L with 80% sensitivity and 82.1% specificity in predicting bone metastases in prostate cancer.

Purpose of review Pathomics, the fusion of digitalized pathology and artificial intelligence, is currently changing the landscape of medical pathology and biologic disease classification. In this review, we give an overview of Pathomics and summarize its most relevant applications in urology. Recent findings There is a steady rise in the number of studies employing Pathomics, and especially deep learning, in urology. In prostate cancer, several algorithms have been developed for the automatic differentiation between benign and malignant lesions and to differentiate Gleason scores. Furthermore, several applications have been developed for the automatic cancer cell detection in urine and for tumor assessment in renal cancer. Despite the explosion in research, Pathomics is not fully ready yet for widespread clinical application. Summary In prostate cancer and other urologic pathologies, Pathomics is avidly being researched with commercial applications on the close horizon. Pathomics is set to improve the accuracy, speed, reliability, cost-effectiveness and generalizability of pathology, especially in uro-oncology.

To determine whether Gleason scores were concordant between prostate biopsies (bGS) and the definitive resection specimen (pGS) excised with robot-assisted radical prostatectomy (RARP); to identify clinical and pathological factors that might predict upgrading; and to evaluate how upgrading affected outcome. Between 2009 and 2016, 25 Belgian centers participated in collecting prospective data for patients that underwent RARP. We analyzed the concordance rate between the bGS and the pGS in 8021 patients with kappa statistics, and we compared concordance rates from different centers. We assessed the effect of several clinical and pathological factors on the concordance rate with logistic regression analysis. The concordance rate for the entire population was 62.9%. Upgrading from bGS to pGS occurred in 27.3% of patients. The number of biopsies was significantly associated with concordance. Older age (>60 y), a higher clinical T stage (≥cT2), a higher PSA value at the time of biopsy (>10 ng/ml), and more time between the biopsy and the radical prostatectomy were significantly associated with a higher risk of upgrading. Positive margins and PSA relapse occurred more frequently in upgraded patients. Center size did not significantly affect the concordance rate (p = 0.40).This prospective, nationwide analysis demonstrated a Gleason score concordance rate of 62.9%. Upgrading was most frequently observed in the non-concordant group. We identified clinical and pathological factors associated with (non)-concordance. Upgrading was associated with a worse oncological outcome. Center volume was not associated with pathological accuracy.

Aim: There is much evidence of an association between cancer and irisin that is an adipokine. This study researched on the relationship between prostate cancer (PCa) and irisin levels, and whether irisin can be used as a biomarker in the diagnosis of PCa. Materials and Methods: For the study groups, 50 primary PCa patients and 30 healthy male subjects were included in the PCa and healthy control groups, respectively. All volunteers in the healthy control group were screened for prostate cancer and other malignancies and chronic diseases. Volunteers who were determine to be completely healthy were included for healthy control group. In the serum samples of the subjects were measured free PSA, total PSA and irisin levels. Irisin levels were compared separately in terms of the Gleason scores and T stage. In addition to intergroup comparisons, the ROC curve for the irisin was plotted and power analysis was performed. Results: Free and total PSA levels in the PCa group were significantly higher compared to the healthy control group (p0.05). When the cut-off value was taken as 8.1, the sensitivity and specificity of irisin for PCa were as 80.5% and 90%, respectively. Conclusion: The results of this study indicate that the levels of irisin in the PCa group are considerably reduced and irisin may be used as a biomarker as well as free and total PSA.

Although growth differentiation factor-15 (GDF-15) is highly expressed in PCa, its role in the development and progression of PCa is unclear. The present study aims to determine the density of GDF-15+ cells and immune cells (M1-/M2 macrophages [MΦ], lymphocytes) in PCa of different Gleason scores (GS) compared to BPH. Immunohistochemistry and double immunofluorescence were performed on paraffin-embedded human PCa and BPH biopsies with antibodies directed against GDF-15, CD68 (M1 MΦ), CD163 (M2 MΦ), CD4, CD8, CD19 (T /B lymphocytes), or PD-L1. PGP9.5 served as a marker for innervation and neuroendocrine cells. GDF-15+ cell density was higher in all GS than in BPH. CD68+ MΦ density in GS9 and CD163+ MΦ exceeded that in BPH. GDF-15+ cell density correlated significantly positively with CD68+ or CD163+ MΦ density in extratumoral areas. Double immunoreactive GDF-15+/CD68+ cells were found as transepithelial migrating MΦ. Stromal CD68+ MΦ lacked GDF-15+. The area of PGP9.5+ innervation was higher in GS9 than in BPH. PGP9.5+ cells, occasionally copositive for GDF-15+, also occurred in the glandular epithelium. In GS6, but not in BPH, GDF-15+, PD-L1+, and CD68+ cells were found in epithelium within luminal excrescences. The degree of extra-/intra-tumoral GDF-15 increases in M1/M2Φ is proposed to be useful to stratify progredient malignancy of PCa. GDF-15 is a potential target for anti-tumor therapy.

Background Studies have shown that human polyomavirus infection may be associated with various human cancers. We investigated the potential relationship between the prevalence of JCPyVor BKPyV and prostate cancer (PC) in patients from Taiwan. Methods Patients with PC and benign prostate hypertrophy (BPH; 76 and 30 patients, respectively) were recruited for this study. Paraffin-embedded tissues and clinical information of the patients were obtained. The tissue sections were used for viral DNA detection and immunohistochemistry analysis was performed for examining viral large T (LT) and VP1 proteins. Regression analysis was used to evaluate the relationship between the clinical characteristics of the patients and the risk of JCPyV/BKPyV infection. Results The prevalence of JCPyV/BKPyV DNA was different in PC and BPH tissues (27/76 [35.52%] and 2/30 [6.7%], respectively, p = 0.003)]. The LT and VP1 proteins were detected in 27 (35.52%) and 29 PC (38.2%) specimens, respectively, but neither protein was detected in BPH samples (p p = 0.003). Patients with PC showing high levels of prostate-specific antigen and high Gleason scores were associated with a high risk of viral infection (ORs 1.1, 95% CI 1.000–1.003; p = 0.045 and ORs 6.18, 95% CI 1.26–30.33, p = 0.025, respectively). The expression of LT protein associated with the risk of PC increased 2923.39-fold (95% CI 51.19–166,963.62, p Conclusions The findings indicate that JCPyV infection in PC cells may be associated with prostate cancer progression and prognosis. Graphical abstract

Objective: Artificial intelligence (AI) offers new opportunities for objective quantitative measurements of imaging biomarkers from positron-emission tomography/computed tomography (PET/CT). Clinical image reporting relies predominantly on observer-dependent visual assessment and easily accessible measures like SUV max, representing lesion uptake in a relatively small amount of tissue. Our hypothesis is that measurements of total volume and lesion uptake of the entire tumour would better reflect the disease`s activity with prognostic significance, compared with conventional measurements. Methods: An AI-based algorithm was trained to automatically measure the prostate and its tumour content in PET/CT of 145 patients. The algorithm was then tested retrospectively on 285 high-risk patients, who were examined using 18F-choline PET/CT for primary staging between April 2008 and July 2015. Prostate tumour volume, tumour fraction of the prostate gland, lesion uptake of the entire tumour, and SUV max were obtained automatically. Associations between these measurements, age, PSA, Gleason score and prostate cancer-specific survival were studied, using a Cox proportional-hazards regression model. Results: Twenty-three patients died of prostate cancer during follow-up (median survival 3.8 years). Total tumour volume of the prostate (p = 0.008), tumour fraction of the gland (p = 0.005), total lesion uptake of the prostate (p = 0.02), and age (p = 0.01) were significantly associated with disease-specific survival, whereas SUV max (p = 0.2), PSA (p = 0.2), and Gleason score (p = 0.8) were not. Conclusion: AI-based assessments of total tumour volume and lesion uptake were significantly associated with disease-specific survival in this patient cohort, whereas SUV max and Gleason scores were not. The AI-based approach appears well-suited for clinically relevant patient stratification and monitoring of individual therapy.

To assess the distinctiveness of serum native thiol (NT), total thiol (TT) and disulfide (SS) levels in PCa patients, we created a new parameter, prostate thiol index (PTI) [tPSA (TTxPVxAge) -1/2 ]. We determined the performance of the PTI on PCa diagnosis. A total of 107 male patients (PCa:65; BPH:42) who were separated according to their Gleason scores, ISUP grades and EAU risk groups and 20 healthy subjects were included. The performances of the tests were determined. The PCa and BPH groups had lower NT and TT levels and higher SS levels than the control group. PCa patients had higher PTI, tPSA, fPSA, PSAD levels, lower fPSA%, PV and PSA-AV levels than BPH patients. TT, PTI, tPSA, fPSA, fPSA%, PSA-AV, PSAD and PV had significant diagnostic performances. PTI had the highest AUC value and accuracy, PSA-AV had the highest specificity, and fPSA had the lowest sensitivity. The performance of the PTI was the best in distinguishing PCa from BPH. PTI, tPSA and PSAD positively and PSA-AV negatively correlated with ISUP grades and EAU groups. TT can contribute to the discrimination of PCa from BPH and PTI may decrease unnecessary biopsies in clinical practice.

In order to see a relationship between gleason scores on histopathology and PSA levels, group of 200 men were studied which included obtaining there cumulative Gleason score and serum PSA levels before surgical intervention. Two groups were obtained, 178 cases with high (6-10) and 22 with low (2-5) Gleason score. Mean S.PSA levels in patients with high gleason score was 128ng/ml (normal range 0 to 5) and mean PSA levels for patients with low scores was 25ng/ml. The group with high gleason score showed greater increase in serum PSA levels than lower gleason score.

The Gleason grading system that was initiated by a surgeon, created by a pathologist and developed by a statistician predated serum PSA testing, systematic 18-gauge needle biopsy protocols and immunohistochemistry. It has undergone a series of modifications, initially by Veterans Administration Cooperative Urological Research Group and later by the International Society of Urological Pathologists following consensus meetings in 2005 and 2014. This review focusses on selected areas of practical difficulty such as borderline grades, cores with different Gleason scores, reporting of percentage pattern 4 and minor high-grade patterns, intraductal carcinoma and the new grading system for prostate cancer. We offer a pragmatic guide to grading prostate carcinoma and explain how precision of grading becomes less important if the pathologist uses judgment to determine the Gleason score most suitable for that patient, communicates this data effectively in the report and helps clinicians interpret the information correctly.

The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA IT distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p

Diagnosis of prostate cancer is based on histologic evaluation of tumor architecture using a system known as the “Gleason score.” This diagnostic paradigm, while the standard of care, is time-consuming, shows intraobserver variability, and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in regions of tissue that appeared histologically benign, possibly suggestive of precancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols, and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support image-guided prostate biopsy. Implications: In this study, we suggest that metabolomic differences between prostate cancers with different Gleason scores can be detected by mass spectrometry imaging.

Histological grading of prostate cancer is one of the most important tissue-based parameters for prediction of outcome and treatment response. Gleason grading remains the foundation of prostate cancer grading, but has undergone a series of changes in the past 30 years, often initiated by consensus conference decisions. This review summarizes the most important modifications that were introduced by the 2005 and 2014 International Society of Urological Pathology (ISUP) revisions of Gleason grading and discusses the impact that these have had on current grading practices. A considerable inflation in Gleason scores has been observed, especially following the ISUP 2005 revision, and the effects of this are discussed. ISUP 2014 grading recommendations are described, including the reporting of ISUP grades 1-5. Controversial issues include methods for reporting of grades on needle biopsies, reporting of percent Gleason grades 4/5 and grading of cribriform and intraductal carcinoma of the prostate. Educational programs developed recently to promote standardization of grading are described and their results assessed.

Background: The majority of studies investigating the role of Ki67 labeling index (LI) in prostate carcinoma (PC) focused on localized PC treated radically, where Ki67 LI is regarded as a prognostic marker. The relevance of Ki67 in advanced PC remains largely unexplored. While Gleason score is still one of the best indicators of clinical outcomes in PC, differences in progression-free survival and overall survival in patients with high Gleason scores suggest that additional factors are involved in tumor progression. Understanding the underlying mechanisms could help to optimize treatment strategies for an individual patient. Here, we aimed to determine the inter- and intratumoral distribution of Ki67 LI in patients with PC with high Gleason scores and to correlate Ki67 LI with the status of ERG, PTEN, and Bcl-2. Methods: Immunohistochemistry for Ki67, ERG, PTEN, and Bcl-2 was performed on core needle biopsies from 112 patients with newly diagnosed PC Gleason score 8, 9, and 10. Results: Using a cutoff of ≥10%, 17/112 cases (15%) had a homogeneously low and 95/112 cases (85%) a high Ki67 LI. 41% of cases showed intratumoral heterogeneity containing areas with low and high proliferation. There was no association between Ki67 LI and ERG, PTEN, or Bcl-2 status. Conclusions: Our data demonstrate major inter- and intratumoral variability of Ki67 LI in high-grade PC with a surprisingly low Ki67 LI in a subset of cases. Further studies are necessary to explore the molecular basis and potential clinical implications of a paradoxically low proliferation rate in high-grade PC.

PURPOSE Tensor-valued diffusion encoding provides more specific information than conventional diffusion-weighted imaging (DWI), but has mainly been applied in neuroimaging studies. This study aimed to assess its potential for the imaging of prostate cancer (PCa). METHODS Seventeen patients with histologically proven PCa were enrolled. DWI of the prostate was performed with linear and spherical tensor encoding using a maximal b-value of 1.5 ms/µm2 and a voxel size of 3 × 3 × 4 mm3 . The gamma-distribution model was used to estimate the mean diffusivity (MD), the isotropic kurtosis (MKI ), and the anisotropic kurtosis (MKA ). Regions of interest were placed in MR-defined cancerous tissues, as well as in apparently healthy tissues in the peripheral and transitional zones (PZs and TZs). RESULTS DWI with linear and spherical encoding yielded different image contrasts at high b-values, which enabled the estimation of MKA and MKI . Compared with healthy tissue (PZs and TZs combined) the cancers displayed a significantly lower MD (P < .05), higher MKI (P < 10-5 ), and lower MKA (P < .05). Compared with the TZ, tissue in the PZ showed lower MD (P < 10-3 ) and higher MKA (P < 10-3 ). No significant differences were found between cancers of different Gleason scores, possibly because of the limited sample size. CONCLUSION Tensor-valued diffusion encoding enabled mapping of MKA and MKI in the prostate. The elevated MKI in PCa compared with normal tissues suggests an elevated heterogeneity in the cancers. Increased in-plane resolution could improve tumor delineation in future studies.

Background and purpose: The aim of this study was to evaluate the potential to increase the tumor control probability (TCP) with 'dose painting by numbers' (DPBN) plans optimized in a treatment planning system (TPS) compared to uniform dose plans. The DPBN optimization was based on our earlier published formalism for prostate cancer that is driven by dose-responses of Gleason scores mapped from apparent diffusion coefficients (ADC). Material and methods: For 17 included patients, a set of DPBN plans were optimized in a TPS by maximizing the TCP for an equal average dose to the prostate volume (CTVT) as for a conventional uniform dose treatment. For the plan optimizations we applied different photon energies, different precisions for the ADC-to-Gleason mappings, and different CTVT positioning uncertainties. The TCP increasing potential was evaluated by the DPBN efficiency, defined as the ratio of TCP increases for DPBN plans by TCP increases for ideal DPBN prescriptions (optimized without considering radiation transport phenomena, uncertainties of the CTVT positioning, and uncertainties of the ADC-to-Gleason mapping). Results: The median DPBN efficiency for the most conservative planning scenario optimized with a low precision ADC-to-Gleason mapping, and a positioning uncertainty of 0.6 cm was 10%, meaning that more than half of the patients had a TCP gain of at least 10% of the TCP for an ideal DPBN prescription. By increasing the precision of the ADC-to-Gleason mapping, and decreasing the positioning uncertainty the median DPBN efficiency increased by up to 40%. Conclusions: TCP increases with DPBN plans optimized in a TPS were found more likely with a high precision mapping of image data into dose-responses and a high certainty of the tumor positioning. These findings motivate further development to ensure precise mappings of image data into dose-responses and to ensure a high spatial certainty of the tumor positioning when implementing DPBN clinically.

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.

Objectives We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort. Methods We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995. We excluded those with seminal vesicle and/or lymphatic involvement. We regraded the specimens according to contemporary guidelines and compared how this affected outcomes compared with their original (pre-1995) Gleason scoring. In total, 499 patients were evaluable. Results A Gleason score of 6 or less declined from 73% to 29%, and the number increased from 25% to 63% for a Gleason score of 7 and from 5% to 8% for a Gleason score of 8 to 9. As a result, for a Gleason score less than 7, biochemical failure decreased from 28% to 23%, metastatic disease 5% to 2%, and prostate cancer death from 5% to 3%. The same results were 50% to 37%, 11% to 7%, and 10% to 6% for a Gleason score of 7 and 86% to 71%, 43% to 32%, and 29% to 26% for a Gleason score more than 7, respectively. With the most recent grade grouping, for groups 1 to 5, biochemical failure occurred in 23%, 32%, 45%, 69%, and 78%, respectively. Metastatic disease occurred in 2%, 4%, 12%, 24%, and 56%, respectively. Prostate cancer–related death occurred in 2%, 4%, 9%, 21%, and 44%, respectively. Conclusions The revised Gleason scores improved the outcomes in all risk groups. Based on Gleason score, patients with prostate cancer will appear to have better outcomes than they did before 2005, making any comparison tenable. The current grading system shows a consistent increased risk in biochemical failure, metastatic disease, and prostate cancer–related death with each successive grade.

OBJECTIVE: To investigate the value of texture analysis in magnetic resonance images for the evaluation of Gleason scores (GS) of prostate cancer. METHODS: Sixty-six prostate cancer patients are retrospective enrolled, which are divided into five groups namely, GS = 6, 3 + 4, 4 + 3, 8 and 9–10 according to postoperative pathological results. Extraction and analysis of texture features in T2-weighted MR imaging defined tumor region based on pathological specimen after operation are performed by texture software OmniKinetics. The values of texture are analyzed by single factor analysis of variance (ANOVA), and Spearman correlation analysis is used to study the correlation between the value of texture and Gleason classification. Receiver operating characteristic (ROC) curve is then used to assess the ability of applying texture parameters to predict Gleason score of prostate cancer. RESULTS: Entropy value increases and energy value decreases as the elevation of Gleason score, both with statistical difference among five groups (F = 10.826, F = 2.796, P

In two studies, gay, bisexual, and other men who have sex with men prostate cancer survivors report lower Gleason scores than heterosexual prostate cancer survivors, leading some to speculate that men who have sex with men may have more intensive screening than other men. In the largest study of men who have sex with men prostate cancer survivors to date, 23 of 193 (11.9%) men who have sex with men prostate cancer survivors reported low Gleason scores (2-5). We contacted 14 of them, a 61 percent response rate. At second interview, most men clarified that they reported only a partial score rather than the sum score. We conclude the average lower score is not a result of differences in screening but likely measurement error. A revised Gleason item question is provided to overcome this research artifact.

Background Numerous studies have assessed the association between xeroderma pigmentosum complementation group C (XPC) polymorphisms and susceptibility of prostate cancer (PCa); however, the findings remain inconsistent. Methods We performed an updated analysis utilizing data from electronic databases to obtain a more accurate estimation of the relationship between XPC rs2228001 A/C polymorphism and PCa risk. We further used in silico tools to investigate this correlation. Results Totally, 5,305 PCa cases and 6,499 control subjects were evaluated. When all studies pooled together, we detected no positive result (recessive genetic model: OR = 1.14, 95% CI = 0.93-1.40, Pheterogeneity = 0.001, P = .212); nevertheless, the XPC rs2228001 A/C variant was associated with PCa risk in Asian descendants in the subgroup analysis (OR = 1.21, 95% CI = 1.01-1.43, Pheterogeneity = 0.008, P = .034). In silico tools showed that more than 20 proteins can participate in the protein crosstalk with XPC. The expression of XPC was down-regulated in all Gleason scores of prostate cancer. Conclusions The present study indicated that the XPC rs2228001 A/C variant may be associated with elevated PCa risk in Asian patients.

Histopathological tissue analysis is the most effective and definitive method to prognosis cancer and stratify the aggressiveness of the disease. The Gleason Score (GS) is the most powerful grading system based on architectural tumor pattern quantification. This score characterizes cancer tumor tissue, such as the level of cell differentiation on histopathological images. The reported GS is described as the sum of two principal grades present in a particular image, and ranged from 6 (cancer grow slowly) to 10 (cancer cells spread more rapidly). A main drawback of GS is the pathological dependency on histopathological region stratification, which strongly impacts the clinical procedure to treat the disease. The agreement among experts has been quantified with a kappa index of: ~0.71. Even worse, a higher uncertainty is reported for intermediate grade stratification. This work presents a like-inception deep architecture that is able to differentiate between intermediate and close GS grades. Each image herein evaluated was split-up into regional patches that correspond to a single GS grade. A set of training patches were augmented according to appearance image variations of each grade. Then, a transfer learning scheme was implemented to adapt a bi-Gleason tumor patterns prediction among close levels. The proposed approach was evaluated on public set of 886 tissue H&E stained images with different GS grades, achieving an average accuracy of 0.73% between grades three and four.

This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 (18F)-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the management of patients with prostate cancer (PCa). Relevant studies regarding 18F-PSMA PET/CT in the management of PCa published until June 1, 2021, were electronically searched in online databases including EMBASE, PubMed, and Web of Science. The primary outcome was the DR of 18F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18F-PSMA PET/CT according to Gleason scores and serum prostate-specific antigen (PSA) level. The pooled DR was calculated on a per-patient basis, with pooled odd ratios and 95% confidence intervals (CIs). In total, 17 observational studies evaluating 1019 patients with PCa met the inclusion criteria. The DR of 18F-PSMA PET/CT was 0.83 (95% CI: 0.78-0.88), in the random-effects model. Subsequently, the analysis of DR of 18F-PSMA PET/CT in PCa patients using Gleason score (≤7 vs ≥8), showed a significant difference in PCa patients. Based on the above results, the higher Gleason score of PCa patients, the higher DR of 18F-PSMA PET/CT. The DR of 18F-PSMA PET/CT in PCa was 0.57 for PSA

Thomas Greither,1,* Kersten Fischer,2,* Gerit Theil,2 Marios Marcou,1,2 Hans-Juergen Holzhausen,3 Katrin Weigelt,4 Ginette Serrero,5,6 David Hicks,5 Binbin Yue,5 Paolo Fornara,2 Bernd Wullich,4 Helge Taubert,4 Sven Wach,4 Verena Lieb4 1Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Halle, Germany; 2Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany; 3Department of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany; 4Department of Urology and Pediatric Urology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 5A&G Pharmaceutical Inc., Columbia, Maryland, USA; 6Program in Oncology, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA *These authors contributed equally to this work Background: GP88/Progranulin is a well-recognized cell growth promoter in different cancers, and elevated serum GP88 levels have been described as negative prognostic factor in breast cancer. However, serum levels in prostate cancer (PCa) patients have not yet been studied. Material and Methods: We analyzed serum GP88 levels by enzyme immunosorbent assay and correlated them with clinicopathological parameters in PCa patients. PCa patients were separated into two groups based on the serum GP88 median level (low ≤44.56 ng/mL or high >44.56 ng/mL) and according to their median age (younger ≤66 years or elder patients >66 years). Results: Low serum GP88 levels were more often detected in younger patients and high levels in elder patients (P=0.018; Fisher’s exact test). PCa patients were separated into three groups, Gleason score (GS) ≤6; GS=7; and GS≥8. In receiver operating characteristic analyses, we could distinguish GS≤6 from GS=7 [area under the curve (AUC): 0.646; P=0.018] and GS≤6 from GS≥8 (AUC: 0.629; P=0.048) but not GS=7 from GS≥8. For survival analysis, GP88 levels were separated into two groups by an optimized cutoff value of 36.92 ng/mL. Using this GP88 stratification, all PCa patients and younger patients with a low serum GP88 level had a significantly better overall survival compared with patients with higher serum GP88 levels (log-rank test P=0.010 and P=0.024). Conclusion: Serum GP88 levels are significantly different depending on age and GS, and they are associated with the prognosis of PCa patients. Keywords: GP88, progranulin, prostate cancer, Gleason score

Purpose: To quantify and compare the expression of stromal elements in prostate adenocarcinoma of different Gleason scores with non-tumor area (control). Methods: We obtained 132 specimens from samples of prostate peripheral and transition zone. We analyzed the following elements of the extracellular matrix: collagen fibers, elastic system, smooth muscle fibers and blood vessels. The tumor area and non-tumor area (control) of the TMA (tissue microarray) were photographed and analyzed using the ImageJ software. Results: The comparison between the tumor area and the non-tumor area showed significant differences between stromal prostate elements. There was an increase of collagen fibers in the tumor area, mainly in Gleason 7. Elastic system fibers showed similar result, also from the Gleason 7. Blood vessels showed a significant increase occurred in all analyzed groups. The muscle fibers exhibited a different behavior, with a decrease in relation to the tumor area. Conclusions: There is a significant difference between the extracellular matrix in prostate cancer compared to the non-tumor area (control) especially in Gleason 7. Important modifications of the prostatic stromal elements strongly correlate with different Gleason scores and can contribute to predict the pathological staging of prostate cancer.

AimTo determine how clinicians use data in contemporary prostate biopsy reports.MethodsA survey was circulated to members of the British Association of Urological Surgeons and the British Uro-oncology Group.ResultsResponses were received from 114 respondents (88 urologists, 26 oncologists). Ninety-seven (94%) use the number of positive cores from each side and 43 (42%) use the % number of positive cores. When determining the number and percentage of positive cores, 72 (71%) would not differentiate between targeted and non-targeted samples. If multiple Gleason Scores (GS) were included in a report, 77 (78%) would use the worst GS even if present in a core with very little tumour, 12% would use the global GS and 10% the GS in the core most involved by tumour. Fifty-five (55%) either never or rarely used perineural invasion for patient management.ConclusionsThe number of positive cores is an important parameter for patient management but may be difficult to determine in the laboratory due to core fragmentation so the biopsy taker must indicate the number of biopsies obtained. Multiple biopsies taken from a single site are often interpreted by clinicians as separate cores when determining the number of positive cores so pathologists should also report the number of sites positive. Clinicians have a non-uniform approach to the interpretation of multiple GS in prostate biopsy reports so we recommend that pathologists also include a single ‘bottom-line’ GS for each case to direct the clinician’s treatment decision.

Recent studies have demonstrated that most patients with mucinous prostatic adenocarcinoma may have a better prognosis than those with conventional prostatic adenocarcinoma; however, the mechanism remains unclear. Loss of phosphatase and tensin homolog (PTEN) expression is known to occur in aggressive high-grade prostatic adenocarcinoma, but expression in mucinous prostatic adenocarcinoma has not been well characterized. In this study, we sought to analyze PTEN expression in mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma. Cases were obtained from the Urologic Pathology files of 3 major academic institutions. Ninety-two cases were identified. PTEN expression was positive in the mucinous component of 79/92 (86%) cases. Concordant positive expression of PTEN between mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma was present in 60/79 (76%) cases. The fact that 86% of cases of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were positive for PTEN despite relatively high Gleason scores is in keeping with the fact that these tumors may be less aggressive than conventional prostatic adenocarcinoma without associated extraluminal mucinous components. In 76% of cases, the expression profiles (PTEN positive or negative) of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were similar to those of the adjacent conventional prostatic adenocarcinoma, implying that they may likely be clonal from a molecular standpoint. In addition, it is highly conceivable that the subset of PTEN-negative mucinous tumors may still have a relatively good prognosis due to a different/PTEN-independent protective pathway or mechanism.

Purpose: Black men are more likely to die as a result of prostate cancer than white men, despite effective treatments that improve survival for clinically significant prostate cancer. We undertook this study to identify gaps in prostate cancer care quality, racial disparities in care, and underlying reasons for poorer quality care. Methods: We identified all black men and random age-matched white men with Gleason scores ≥ 7 diagnosed between 2006 and 2013 at two urban hospitals to determine rates of treatment underuse. Underuse was defined as not receiving primary surgery, cryotherapy, or radiotherapy. We then interviewed treating physicians about the reasons for underuse. Results: Of 359 black and 282 white men, only 25 (4%) experienced treatment underuse, and 23 (92%) of these were black. Most (78%) cases of underuse were due to system failures, where treatment was recommended but not received; 38% of these men continued receiving care at the hospitals. All men with treatment underuse due to system failures were black. Conclusion: Treatment rates of prostate cancer are high. Yet, racial disparities in rates and causes of underuse remain. Only black men experienced system failures, a type of underuse amenable to health information technology–based solutions. Institutions are missing opportunities to use their health information technology capabilities to reduce disparities in cancer care.

Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0-51% for the learning set and by 4-30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.