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Simple Summary: Though intraductal carcinoma of the prostate has been observed and recognized for years, more recently this process has emerged, to become simultaneously both a consensus, major prognostic factor and controversial parameter as relates to potential impact on the histologic grading in prostate cancer. Due to the increasing incorporation of intraductal carcinoma into risk stratification approaches and management considerations in this disease, the differential diagnoses of this lesion have become of increasing importance. Herein, we review the background of recognition of and evolution of the criteria for intraductal carcinoma, emphasizing its differential diagnoses, both neoplastic and non-neoplastic. We furthermore recommend useful immunohistochemical markers to help correctly recognize and diagnose this key process. Despite its first recognition even longer ago, in the past nearly 20 years, intraductal carcinoma of the prostate has become a standard histopathologic reporting parameter conveying a strong negative prognostic factor for prostatic adenocarcinoma. When seen at biopsy, intraductal carcinoma of the prostate is associated with risk for aggressive prostatectomy outcomes, including frequently high-grade, high-stage, high-volume disease, with increased risk for recurrence and progression. Multiple organizations, including the uropathology subspecialty societies to the World Health Organization, recognize and recommend reporting the presence of intraductal carcinoma, whether sampled in "pure" form or present with concomitant invasive adenocarcinoma. Moreover, emerging scholarship relates intraductal carcinoma to higher prevalence of homologous recombination repair deficiency mutations in prostatic adenocarcinoma, whether somatic or germline, which serve as indications for approved targeted therapies. Taken together, this is a diagnosis for the histopathologist not to miss. In view of these elevated stakes and the opportunity to further precision medicine, this review details neoplastic and non-neoplastic simulants in the differential diagnosis of intraductal carcinoma of the prostate. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PC) is the most common cancer and the second that causes death in the US. The means of PC treatment have improved with the low-risk disease for men. The Gleason system grading that comprises the Gleason score and Gleason pattern is the primary measurement to assess PC using pathological data, as well as grade groups. We have developed an automated diagnostic deep learning system for the Gleason system, which significantly affects the final treatment and is considered a valuable decision-support tool for PC patients. In this work, we introduced an automated diagnostic system for Gleason system grading and grade groups (GG) classification using whole slide images (WSIs) of digitized prostate biopsy specimens (PBSs). Our system first classifies the Gleason pattern (GP) from PBSs and then identifies the Gleason score (GS) and GG. We developed a comprehensive DL-based approach to develop a grading pipeline system for the digitized PBSs and consider GP as a classification problem (not segmentation) compared to current research studies (deals with as a segmentation problem). A multilevel binary classification was implemented to enhance the segmentation accuracy for GP. Also, we created three levels of analysis (pyramidal levels) to extract different types of features. Each level has four shallow binary CNN to classify five GP labels. A majority fusion is applied for each pixel that has a total of 39 labeled images to create the final output for GP. The proposed framework is trained, validated, and tested on 3080 WSIs of PBS. The overall diagnostic accuracy for each CNN is evaluated using several metrics: precision (PR), recall (RE), and accuracy, which are documented by the confusion matrices.The results proved our system's potential for classifying all five GP and, thus, GG. The overall accuracy for the GG is evaluated using two metrics, PR and RE. The grade GG results are between 50% to 92% for RE and 50% to 92% for PR. Also, a comparison between our CNN architecture and the standard CNN (ResNet50) highlights our system's advantage. Finally, our deep-learning system achieved an agreement with the consensus grade groups. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the association of ISUP/WHO-grade groups with various pathological prognostic parameters and cancer-specific survival in patients with prostatic adenocarcinoma. We found 27 (15.7%) cases of grade group 1, 22 (12.8%) grade group 2, 30 (17.4%) grade group 3, 40 (23.3%) grade group 4 and 53 (30.8%) grade group 5 prostatic adenocarcinoma. We found that high-grade tumors (grade 3–5) had a higher frequency of perineural invasion and higher tumor volumes (>50%). Moreover, a significant association of tumor grade was noted with cancer-specific survival of patients, signifying prognostic significance of grade grouping in prostatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations. [ABSTRACT FROM AUTHOR]

Cancer pathology reports can be complex due to multiple data elements, variability in terminology, and increasing recognition of emerging diagnostic entities. However, treatment may be significantly influenced by histologic subtype, histologic grade, and pathologic tumor stage. We review the clinical utility of pathology data for prostate and kidney cancers, with emphasis on main decision-making points. Key parameters that affect management of prostate cancer in the biopsy setting include Grade Group, percentage of pattern 4, and sometimes extent of involvement. Histologic subtypes mostly do not affect management, with exceptions of small cell carcinoma and sometimes cribriform/intraductal carcinoma. For renal cancer, histologic subtype, tumor grade, and tumor stage are important for prognostication. Confirming a diagnosis of renal cell carcinoma and recognition of clear cell, non-clear cell, and select other histologies are important in the metastatic setting for treatment selection. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the new prostate cancer grade groups model provides significant predictive value and better patient stratification on tumor progression after radical prostatectomy compared with the former Gleason grading models. Methods: Men treated at a tertiary center by radical prostatectomy between 2005 and 2017 were analyzed. The outcomes of interest were clinical progression‐free and cancer‐specific survival. Multivariate Cox regression analysis, C‐index and decision curve analysis were carried out using three‐tier (Gleason score 6, 7 and 8–10), four‐tier (Gleason score 6, 7, 8 and 9–10) and new grade groups model. Results: In total, 1759 men were included in the analysis. At a median of 87 months (interquartile range 51–134 months) of follow up, clinical progression was detected in 78 (4.4%) and cancer‐related death in 42 (2.4%) patients. The hazard ratio of clinical progression‐free was 2.3, 5.7, 5.2 and 29.5; the hazard ratio of cancer‐specific survival was 1.7, 3.2, 4.8 and 11.8 in the grade groups 2–5, relative to grade group 1, respectively. The grade groups model had higher C‐index in comparison with four‐ and three‐tier grading models for clinical progression‐free survival 0.88 versus 0.85 versus 0.83 and for cancer‐specific survival 0.82 versus 0.80 versus 0.80, respectively. In the decision curve analysis, the grade groups model shows marginally better net benefit on clinical progression‐free and cancer‐specific survival. Conclusions: The new model shows better performance in comparison with former Gleason grading models on the prediction of long‐term oncological outcomes. [ABSTRACT FROM AUTHOR]

Keywords: cribriform; intraductal carcinoma; prostate cancer; outcomes; Grade Groups; germline testing; PTEN EN cribriform intraductal carcinoma prostate cancer outcomes Grade Groups germline testing PTEN 1038 1040 3 05/24/22 20220601 NES 220601 In recent years, cribriform morphology has become a hotly debated histological pattern in prostate cancer pathology. One largely unexplored area is the molecular changes specific to cribriform prostate cancer and its tumor microenvironment.10,15 Challenges for research in this area include the imprecise gathering of fresh prostate cancer from radical prostatectomy specimens. Diagnostic accuracy of prostate biopsy for detecting cribriform Gleason pattern 4 carcinoma and intraductal carcinoma in paired radical prostatectomy specimens: Implications for active surveillance. In addition, due to the well-documented issues with sampling cribriform prostate cancer and the poor detection rate on biopsy,16,17 studies that choose to use prostate biopsies as a method of understanding the biologic potential and clinical significance of these tumors may be misleading. [Extracted from the article]

The aim of study was to explore the correlation between shear wave elastography (SWE) and grade group (GG) of prostate cancer (PCa). This retrospective study involved prostate-specific antigen elevated patients with elevated prostate-specific antigen levels who underwent SWE before transrectal ultrasound-guided needle biopsy. A total of 49 PCa lesions were reviewed after radical prostatectomy; 3-7 regions of interest were placed within the cancerous area on axial view compared with the tumor foci outlined on the slides by pathologist. The maximum SWE value was measured, quantitative SWE parameters (Emax, Emean, Emin and standard deviation [SD]) were recorded and correlated with GG and then parameters were compared between indolent (≤2) and aggressive (≥3) GGs. The diagnostic value of each parameter was compared with the receiver operating characteristic curve. Forty-nine PCa foci were divided into two groups on the basis of their GGs. All SWE parameters exhibited a significant linear trend with GG. The area under the receiver operating characteristic curve (AUC) was 0.816 for Emax; with a cutoff point of 84 kPa, sensitivity and specificity were 81.3% and 82.4% to differentiate low and high GGs in PCa. The AUC was 0.776 for Emean; with a cutoff point of 71 kPa, sensitivity and specificity were 78.1% and 76.5%. For Emin, the AUC was 0.739; with a cutoff point of 60 kPa, sensitivity and specificity were 68.8% and 70.6%. For SD, the AUC was 0.681; with a cutoff point of 8.3 kPa, sensitivity and specificity were 46.9% and 94.1%. There were no significant differences between the four SWE parameters (p < 0.05 for all). SWE features were correlated with GGs, and this correlation may have excellent diagnostic performance in predicting high GG in PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer is a significant cause of morbidity and mortality in the USA. In this paper, we develop a computer-aided diagnostic (CAD) system for automated grade groups (GG) classification using digitized prostate biopsy specimens (PBSs). Our CAD system aims to firstly classify the Gleason pattern (GP), and then identifies the Gleason score (GS) and GG. The GP classification pipeline is based on a pyramidal deep learning system that utilizes three convolution neural networks (CNN) to produce both patch- and pixel-wise classifications. The analysis starts with sequential preprocessing steps that include a histogram equalization step to adjust intensity values, followed by a PBSs’ edge enhancement. The digitized PBSs are then divided into overlapping patches with the three sizes: 100 × 100 (CNNS), 150 × 150 (CNNM), and 200 × 200 (CNNL), pixels, and 75% overlap. Those three sizes of patches represent the three pyramidal levels. This pyramidal technique allows us to extract rich information, such as that the larger patches give more global information, while the small patches provide local details. After that, the patch-wise technique assigns each overlapped patch a label as GP categories (1 to 5). Then, the majority voting is the core approach for getting the pixel-wise classification that is used to get a single label for each overlapped pixel. The results after applying those techniques are three images of the same size as the original, and each pixel has a single label. We utilized the majority voting technique again on those three images to obtain only one. The proposed framework is trained, validated, and tested on 608 whole slide images (WSIs) of the digitized PBSs. The overall diagnostic accuracy is evaluated using several metrics: precision, recall, F1-score, accuracy, macro-averaged, and weighted-averaged. The (CNNL) has the best accuracy results for patch classification among the three CNNs, and its classification accuracy is 0.76. The macro-averaged and weighted-average metrics are found to be around 0.70–0.77. For GG, our CAD results are about 80% for precision, and between 60% to 80% for recall and F1-score, respectively. Also, it is around 94% for accuracy and NPV. To highlight our CAD systems’ results, we used the standard ResNet50 and VGG-16 to compare our CNN’s patch-wise classification results. As well, we compared the GG’s results with that of the previous work.

Abstract Background A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists. Methods Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression. Results For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5–3.6); 2.5 (1.6–4.2); 4.1 (2.6–6.7) and 8.7 (4.5–14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9–10) respectively, relative to grade group I (total score

The role of DNA MMR genes in prostate cancer (PrCa) is controversial, as genetic alterations leading to microsatellite instability are incompletely defined in these tumors. ERG rearrangements and PTEN loss are concomitant events in PrCa. The aim of this study has been to analyze the immunohistochemical (IHC) expression of MSH2, MSH6, MLH1, PMS2, ERG, and PTEN and their potential association with the grade group (GG) grading system (WHO 2016) and PSA recurrence in a series of 200 PrCa (PSMAR-Biobank, Barcelona, Spain). MSH2, MLH1, PMS2, and PTEN losses were documented in 8%, 5%, 2%, and 36.5%, respectively. ERG expression was found in 48%. MSH6 showed an increase of expression with respect to basal levels in 42.1% of the cases. A statistical association between MSH6 overexpression and GG5 was found (p = 0.0281). ERG-wild-type cases were associated with single MSH2 loss (p = 0.024), and MSH2 and/or MLH1 loss (p = 0.019). The percentage of cases with PTEN loss was 20.5% (8/39) in GG1, 37.6% (53/141) of clustered GG2 to 4, and 60% (12/20) of GG5 (chi-square test, p = 0.01). Thus, PTEN expression loss was statistically more frequent in the upper-grade tumors. PMS2 loss was an infrequent event, but it was statistically associated with shorter time to PSA recurrence (p = 0.011). These results suggest the existence of an alternative non-ERG pathway associated with MSH2 or MLH1 expression loss. MSH6 overexpression could be a marker of aggressiveness in PrCa. The IHC assessment of DNA MMR proteins, ERG and PTEN, could identify different altered PrCa pathways, which could aid patient stratification. [ABSTRACT FROM AUTHOR]

Histopathologic grading of prostate cancer using Gleason patterns (GPs) is subject to a large inter-observer variability, which may result in suboptimal treatment of patients. With the introduction of digitization and whole-slide images of prostate biopsies, computer-aided grading becomes feasible. Computer-aided grading has the potential to improve histopathological grading and treatment selection for prostate cancer. Automated detection of GPs and determination of the grade groups (GG) using a convolutional neural network. In total, 96 prostate biopsies from 38 patients are annotated on pixel-level. Automated detection of GP 3 and GP ≥ 4 in digitized prostate biopsies is performed by re-training the Inception-v3 convolutional neural network (CNN). The outcome of the CNN is subsequently converted into probability maps of GP ≥ 3 and GP ≥ 4, and the GG of the whole biopsy is obtained according to these probability maps. Differentiation between non-atypical and malignant (GP ≥ 3) areas resulted in an accuracy of 92% with a sensitivity and specificity of 90 and 93%, respectively. The differentiation between GP ≥ 4 and GP ≤ 3 was accurate for 90%, with a sensitivity and specificity of 77 and 94%, respectively. Concordance of our automated GG determination method with a genitourinary pathologist was obtained in 65% (κ = 0.70), indicating substantial agreement. A CNN allows for accurate differentiation between non-atypical and malignant areas as defined by GPs, leading to a substantial agreement with the pathologist in defining the GG. [ABSTRACT FROM AUTHOR]

Aims: Comedonecrosis in prostate cancer has always been Gleason pattern 5. However, we aimed to evaluate how intraductal carcinoma (not graded) with comedonecrosis should be considered. Methods and results: From 52 radical prostatectomy patients, 40 were informative and evaluated with immunohistochemistry for basal cells. Clinical outcome was assessed for biochemical recurrence, metastatic disease and the need for adjuvant therapy. Comedonecrosis was predominantly located in intraductal carcinoma (24, 60%). However, nine (23%) had comedonecrosis within invasive cancer and seven (18%) within both invasive and intraductal carcinoma. Extraprostatic extension rarely showed comedonecrosis (5, 13%), but rather perineural invasion within cribriform glands. Tumours were largely high‐stage (15, 38% pT3a and 19, 48% pT3b), with 15 (37%) having positive lymph nodes and four distant metastases. Most cases (25, 63%) had other patterns of Gleason pattern 5 (single cells, solid), although 10 were reclassified as containing no invasive pattern 5. Of these, most were pT3 (eight of 10), but none had positive lymph nodes. Lymph node metastases were more common in patients with invasive cancer containing comedonecrosis (P = 0.02), and the need for androgen deprivation was near significance (P = 0.07), but biochemical recurrence was not significantly different (P = 0.58). Conclusions: Prostate cancer with comedonecrosis is often intraductal; however, these tumours are largely high‐stage, showing a higher rate of positive lymph nodes with invasive comedonecrosis. Immunohistochemistry may be considered when comedonecrosis may significantly change the tumour grade. However, it is not clear at present that excluding intraductal carcinoma from the grade is superior to including it in grading when it is associated with high‐grade invasive cancer. [ABSTRACT FROM AUTHOR]

Abstract Background A new prostate cancer grading system was proposed in 2013 and endorsed by major journals and societies in 2014, in part because of anecdotal evidence that Gleason scores (GSs) were incorrectly combined in the literature. Objective To examine how published studies categorized GSs in current practice. Design, setting, and participants A PubMed search was conducted on articles published in 2016–2017 using the search terms "Gleason" and "prostate". This literature review included 1576 articles after exclusions. Results (1) Separating GS 7: pathology journals were more likely than non-pathology journals to grade GS 7 separately (56.9% vs 40.0%, p < 0.05). Articles co-authored by a pathologist separated GS 7 more than those without a pathologist (53.2% vs 32.9%, p < 0.001). North American and European studies separated GS 7 more than Asian studies (47.6% and 44.1% vs 24.1%, p < 0.001). Clinical articles separated GS 7 more than research articles (43.7% vs 32.9%, p < 0.001). (2) Separating GS 8 from GS 9–10: pathology journals separated GS 8 from GS 9–10 more than non-pathology journals (55.2% vs 34.4%, p = 0.001). Articles co-authored by a pathologist separated GS 8 from GS 9–10 more often than those without a pathologist (44.9% vs 29.5%, p < 0.001). (3) Using grade groups as "ideal" with all other groupings "non-ideal": pathology journals used ideal more than non-pathology journals (32.2% vs 15.9%, p < 0.001). Ideal grouping is more likely in articles co-authored by a pathologist than in those without a pathologist (20.6% vs 11.0%, p < 0.001). North American and European studies used ideal grouping more than Asian studies (17.6% and 14.0% vs 9.1%, p < 0.05). (4) Arranging groupings in decreasing order from ideal to non-ideal: pathology journals were closer to ideal than non-pathology journals (p = 0.002). Articles co-authored by a pathologist were classified closer to ideal than those without a pathologist (p < 0.001). North American (p < 0.001) and European (p = 0.02) studies were closer to ideal than Asian studies. Conclusions There is still wide variation in how GSs are grouped world-wide. Only a minority of published articles group GSs accurately. Patient summary In this report, we looked at how GSs were grouped world-wide. We found that only a minority of published articles on prostate cancer were grouping GSs accurately, which could lead to inaccurate results and affect patient care with different prostate cancer grades. Our study calls for more widespread adoption of the new prostate cancer grading system composed of five grade groups to minimize incorrect grouping for future studies. Take Home Message There is still wide variation in how Gleason scores are grouped world-wide. Only a minority of published articles are grouping Gleason scores accurately. Our study calls for more widespread adoption of grade groups to minimize incorrect grouping for future studies. [ABSTRACT FROM AUTHOR]

Background: Observational data and funnel plots are routinely used outside of pathology to understand trends and improve performance. Objective: Extract diagnostic rate (DR) information from free text surgical pathology reports with synoptic elements and assess whether inter-rater variation and clinical history completeness information useful for continuous quality improvement (CQI) can be obtained. Methods: All in-house prostate biopsies in a 6-year period at two large teaching hospitals were extracted and then diagnostically categorized using string matching, fuzzy string matching and hierarchical pruning. DRs were then stratified by the submitting physicians and pathologists. Funnel plots were created to assess for diagnostic bias. Results: 3,854 prostate biopsies were found and all could be diagnostically classified. Two audits involving the review of 700 reports and a comparison of the synoptic elements with the free text interpretations suggest a categorization error rate of <1%. Twenty-seven pathologists each read >40 cases and together assessed 3,690 biopsies. There was considerable inter-rater variability and a trend toward more World Health Organization/International Society of Urologic Pathology Grade 1 cancers in older pathologists. Normalized deviations plots, constructed using the median DR, and standard error can elucidate associated over-and under-calls for an individual pathologist in relation to their practice group. Clinical history completeness by submitting medical doctor varied significantly (100% to 22%). Conclusion: Free text data analyses have some limitations; however, they could be used for data-driven CQI in anatomical pathology and could lead to the next generation in quality of care. [ABSTRACT FROM AUTHOR]

In 2016, the grading criteria for Gleason scoring ( GS) have been updated in the WHO classification of tumors of the prostate, and a new set of grade groups ( GG) was introduced. As the inter-observer discordance is a well-known concern in Gleason grading before the update and no reproducibility study testing the grade groups exists, we planned to evaluate the inter-observer agreement of the most updated grading system. Four pathologists assessed 126 cores of prostatic carcinoma, and Kappa (k) test was calculated. The agreements for both GS and GG were substantial (k = 0.753 and 0.752; respectively). Discerning GG 2 from 3 also attained reasonable outcome (k = 0.675). Based on our results, the updated grading system seems to be reproducible, with satisfactory inter-observer concordance rate. [ABSTRACT FROM AUTHOR]

Background: A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists.Methods: Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression.Results: For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5-3.6); 2.5 (1.6-4.2); 4.1 (2.6-6.7) and 8.7 (4.5-14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9-10) respectively, relative to grade group I (total score < =6). Clear gradients in risk of PCa death were observed for radical prostatectomy (RP), but were less clear for those who had radiotherapy (RT) with curative intent and those who were managed conservatively. Likewise, risk of biochemical recurrence increased across grade groups, with a strong and clear gradient for men undergoing RP [sHR (95%CI): 2.0 (1.4-2.8); 3.8 (2.9-5.9); 5.3 (3.5-8.0); 11.2 (6.5-19.2) for grade groups II, III, IV and V respectively, relative to grade group I], and a less clear gradient for men undergoing RT.Conclusion: In general, the new five-tiered grade groupings distinguished PCa survival and recurrence outcomes for men with PCa. The absence of a clear gradient for RT may be due to heterogeneity in this patient group. [ABSTRACT FROM AUTHOR]

Objectives To determine the risk of pelvic lymph node ( LN) metastases at radical prostatectomy ( RP) for Gleason score ( GS) ≤7: 3 + 3 = 6 (grade group [ GG]1); 3 + 4 = 7 ( GG2); 3 + 4 = 7 ( GG2) with tertiary pattern 5 (T5); 4 + 3 = 7 ( GG3); 4 + 3 = 7 ( GG3) with T5, using the 2014 modified Gleason grading system and the novel GG system. Materials and Methods We searched our RP database to indentify cases of GS ≤7 prostate cancer with simultaneous pelvic LN dissection ( PLND) in the period between 2005 and 2014. Since 2005, we have graded all glomeruloid and cribriform cancer as Gleason pattern 4 and have graded mucinous adenocarcinoma based on the underlying architectural pattern, consistent with the 2014 modified Gleason grading system. All RPs were embedded in entirety, including the PLND. A total of 7 442 cases were identified, of which 73 had at least one positive LN (+ LN). Results The incidence rates for regional LN metastases at RP for 3 + 3 = 6 ( GG1), 3 + 4 = 7 ( GG2), 3 + 4 = 7 ( GG2) with T5, 4 + 3 = 7 ( GG3) and 4 + 3 = 7 ( GG3) with T5 were 0, 0.6, 0.4, 4.3 and 6.3%, respectively. There was a statistically significant difference in risk of + LNs at RP between the grade groups, as defined by the novel GG system. There was no statistically significant difference in risk of + LNs at RP for men with 3 + 4 ( GG2) vs 3 + 4 ( GG2) with T5 and for men with 4 + 3 ( GG3) vs 4 + 3 ( GG3) with T5. Non-pelvic LN involvement was identified in 0.2% of all RP cases. Two patients with GS 3 + 4 = 7 with <5% pattern 4 experienced LN metastases. Conclusion This study supports our previous finding that men with GS 6 ( GG1) at RP have no risk of LN metastases. These findings also support the 2014 revisions to the Gleason grading system where 3 + 3 with T4 (2005 modified grading system) is now considered 3 + 4 ( GG2), with a comment on percent pattern 4, because <5% pattern 4 increases the risk of LN metastases. It also supports keeping 3 + 4 ( GG2) with T5 (<5% pattern 5) and 4 + 3 ( GG3) with T5 with their respective grade groups, with a notation of T5 because the <5% higher grade component did not increase the risk of LN metastases within a given GG. Our findings highlight that 3 + 4 ( GG2) and 4 + 3 ( GG3), even with a 5% higher grade component, are distinct groups with respect to LN metastases and should not be combined under the umbrella designation of GS 7 as is often the case in the literature with the Gleason grading system. [ABSTRACT FROM AUTHOR]

Since its initial description in 1966 by Dr Donald Gleason, Gleason grading has become the cornerstone in the management of prostate cancer (PCa). With widespread use of Prostate Specific Antigen (PSA) screening and needle core biopsy, the diagnosis and management of PCa have dramatically evolved. In addition, better understanding of the morphological spectrum of prostate cancer and its clinical significance have prompted the refinement of the grading criteria and reporting guidelines commensurate to contemporary practice. The modification of the Gleason grading system implemented by the International Society of Urological Pathology in 2005 and subsequent revision in 2014 has profoundly impacted how PCa is graded and managed. This review aims to provide a concise update on the refinement of the histological criteria for various Gleason patterns and problem areas of Gleason grading, and provide recommendations on how to improve the grading reproducibility. The new proposal to group Gleason scores into clinically meaningful 'grade groups' will also be discussed. Finally, we will discuss how magnetic resonance imaging (MRI)-targeted biopsy and emerging genetic markers may help improve the Gleason grading accuracy and risk stratification currently based on clinicopathological parameters. [ABSTRACT FROM AUTHOR]

The Gleason scoring system and Grade Group systems facilitate accurate grading and reporting of prostate cancer, which are essential tasks for surgical pathologists. Gleason Pattern 4 is critical to recognize because it signifies a risk for more aggressive behavior than Gleason Pattern 3 carcinoma. Prostatic adenocarcinoma with radiation or androgen therapy effect, with aberrant P63 expression, or with Paneth cell-like differentiation represent pitfalls in prostate cancer grading because although they display architecture associated with aggressive behavior in usual prostatic adenocarcinoma, they do not behave aggressively and using conventional Gleason scoring in these tumors would significantly overstate their biologic potential., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prostate cancer is a significant cause of morbidity and mortality in the USA. In this paper, we develop a computer-aided diagnostic (CAD) system for automated grade groups (GG) classification using digitized prostate biopsy specimens (PBSs). Our CAD system aims to firstly classify the Gleason pattern (GP), and then identifies the Gleason score (GS) and GG. The GP classification pipeline is based on a pyramidal deep learning system that utilizes three convolution neural networks (CNN) to produce both patch- and pixel-wise classifications. The analysis starts with sequential preprocessing steps that include a histogram equalization step to adjust intensity values, followed by a PBSs' edge enhancement. The digitized PBSs are then divided into overlapping patches with the three sizes: 100 × 100 ( C N N S ), 150 × 150 ( C N N M ), and 200 × 200 ( C N N L ), pixels, and 75% overlap. Those three sizes of patches represent the three pyramidal levels. This pyramidal technique allows us to extract rich information, such as that the larger patches give more global information, while the small patches provide local details. After that, the patch-wise technique assigns each overlapped patch a label as GP categories (1 to 5). Then, the majority voting is the core approach for getting the pixel-wise classification that is used to get a single label for each overlapped pixel. The results after applying those techniques are three images of the same size as the original, and each pixel has a single label. We utilized the majority voting technique again on those three images to obtain only one. The proposed framework is trained, validated, and tested on 608 whole slide images (WSIs) of the digitized PBSs. The overall diagnostic accuracy is evaluated using several metrics: precision, recall, F1-score, accuracy, macro-averaged, and weighted-averaged. The ( C N N L ) has the best accuracy results for patch classification among the three CNNs, and its classification accuracy is 0.76. The macro-averaged and weighted-average metrics are found to be around 0.70–0.77. For GG, our CAD results are about 80% for precision, and between 60% to 80% for recall and F1-score, respectively. Also, it is around 94% for accuracy and NPV. To highlight our CAD systems' results, we used the standard ResNet50 and VGG-16 to compare our CNN's patch-wise classification results. As well, we compared the GG's results with that of the previous work. [ABSTRACT FROM AUTHOR]

Simple Summary: In 2021, the identification of effective biomarkers became a major focus of prostate cancer (PCa) in order to improve outcomes and select potentially responsive patients. The aim of this contribution is to review the main 2021 novelties in prognostic and therapeutic markers in PCa, with special reference to PCa grading, aggressive variant PCa and molecular markers predicting significant disease or response to therapy. The 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic evaluation only, i.e., PCa grading, and the other involving both morphologic and immunohistochemical evaluations, i.e., aggressive variant PCa (AVPCa). Grading concerns androgen-dependent PCa, while AVPCa represents a late phase in its natural history, when it becomes androgen-independent. The novelties of the other major group are related to molecular markers predicting significant disease or response to therapy. This group mainly includes novelties in the molecular evaluation of PCa in tissue material and liquid biopsies. [ABSTRACT FROM AUTHOR]

Simple Summary: For prostate cancer patient, information on risk of long-term cancer-specific and other-cause mortality is essential to avoid over- and undertreatment. Patient stratification to low-, intermediate-, and high-risk groups has been used for decades. However, recent evidence has shown that such stratification is not optimal and outcomes differ widely, especially in high-risk prostate cancer patients. Gleason score grading is an important factor for the prediction of cancer-specific survival and has been included in all prostate cancer risk stratification models. Moreover, this parameter could be used as an independent predictor. Recently proposed grade group model demonstrated good predictive probability on short-term outcomes. However, there is a lack of data regarding long-term cancer-specific survival. In the presented study, we analyzed long-term oncological outcomes in different grade groups. Detected ratio between cancer-specific and other-cause mortality could be very informative and helpful in prostate cancer patient risk stratification and more precise clinical decision making. Objective: To assess the risk of cancer-specific mortality (CSM) and other-cause mortality (OCM) using post-operative International Society of Urological Pathology Grade Group (GG) model in patients after radical prostatectomy (RP). Patients and Methods: Overall 1921 consecutive men who underwent RP during 2001 to 2017 in a single tertiary center were included in the study. Multivariate competing risk regression analysis was used to identify significant predictors and quantify cumulative incidence of CSM and OCM. Time-depending area under the curve (AUC) depicted the performance of GG model on prediction of CSM. Results: Over a median follow-up of 7.9-year (IQR 4.4-11.7) after RP, 235 (12.2%) deaths were registered, and 52 (2.7%) of them were related to PCa. GG model showed high and stable performance (time-dependent AUC 0.88) on prediction of CSM. Cumulative 10-year CSM in GGs 1 to 5 was 0.9%, 2.3%, 7.6%, 14.7%, and 48.6%, respectively; 10-year OCM in GGs was 15.5%, 16.1%, 12.6%, 17.7% and 6.5%, respectively. The ratio between 10-year CSM/OCM in GGs 1 to 5 was 1:17, 1:7, 1:2, 1:1, and 7:1, respectively. Conclusions: Cancer-specific and other-cause mortality differed widely between GGs. Presented findings could aid in personalized clinical decision making for active treatment. [ABSTRACT FROM AUTHOR]

The aim of the current study was to test whether the grade group assessed in the index tumor nodule predicts biochemical recurrence after surgery. The study cohort series included 144 consecutive patients treated by laparoscopic radical prostatectomy. The following parameters were evaluated in each case: type of radical prostatectomy (with/without lymphadenectomy), pT and pN status, histologic type of prostate carcinoma (acinar versus mixed histology), surgical margin resection status, perineural invasion, lymphovascular invasion, biochemical recurrence status, presence of tertiary Gleason 5 pattern, and grade group that was assessed both in overall prostate cancer and in index (dominant) tumor nodule. Twenty patients (13.9%) experienced postoperative biochemical recurrence at a mean follow-up time of 12.2 months. The univariate survival analysis selected type of radical prostatectomy, histological subtype, lymphovascular invasion, American Joint Committee on Cancer pT and pN classification, tertiary Gleason 5 pattern, preoperative serum prostate specific antigen level, and the grade group assessed in both the overall prostate and index tumor nodule as significant for biochemical recurrence-free survival. Type of radical prostatectomy (P = .020), histological subtype (P = .002), lymphovascular invasion (P = .023), tertiary Gleason pattern 5 (P = .016), and grade group classification in index tumor nodule (P ≤ .0001) were selected as independent predictors of biochemical recurrence-free survival. In conclusion, our results validate grade group in the index tumor nodule as an independent predictor of biochemical recurrence-free survival, thus emphasizing the value of reporting grade group in index tumor nodule. The main limitation of our study is the relatively low number of cases in the current series, suggesting the need of large confirmatory studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort., Methods: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression., Results: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903)., Conclusion: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa., (© 2019 Wiley Periodicals, Inc.)

Authors aimed to assess the correlation between the apparent diffusion coefficient (ADC of the tumor, ADC ratio) and final grade group (GG) after radical prostatectomy (RP), and to determine the threshold values of ADC for detecting clinically significant prostate cancer (PC) with subsequent evaluation in a prospective group. 118 patients with PC were included in the retrospective group. These patients underwent RP from 2012 to 2017 with preoperative 3 Tesla multiparametric MRI (mpMRT) with contrast enhancement in a single center. After analyzing all the MRI studies, the average values of tumor ADC and benign tissue ADC were calculated using the maps of ADC. The prospective part of the study included 60 patients with completed pre-biopsy mpMRI and subsequent RP from January 2018 to March 2019. The prospective part of the study demonstrated the effectiveness of applying the obtained diffusion coefficient thresholds. When used as a criterion for determining clinically significant prostate cancer (GG > 6), threshold value of ADC ratio had sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84%, 91%, 87%, 94% and 78% respectively.

Objectives: To assess management choices in patients who undergo magnetic resonance imaging (MRI)/ultrasound (MRI/US) fusion-guided prostate biopsy compared to patients who undergo systematic biopsy.Methods: We compared men who underwent MRI/US fusion-guided prostate biopsy to those who underwent systematic 12-core biopsy from 2014 to 2016. Patient demographics and pathologic findings were reviewed. The highest grade group per case was considered for analysis.Results: Follow-up was available on 133 patients who underwent MRI/US targeted biopsy and 215 patients who underwent systematic biopsy. There was no difference in prebiopsy prostate-specific antigen (PSA) (10.1 ± 10.0 vs. 12.9 ± 20.5, P = 0.11) between the 2 cohorts. Patients in the MRI cohort were more likely to have had a previous prostate biopsy (P<0.0001). Overall, more patients in the MRI cohort choose active surveillance compared to the standard cohort (49.6% vs. 24.2%, P<0.0001), confirmed on multivariate logistic regression model adjusting for age, PSA density, prior biopsy history, race, grade group, and provider (P = 0.013). This finding held true independently for patients with grade groups 1 and 2 tumors (P = 0.02 and P = 0.005, respectively) and in a multivariate logistic regression model adjusting for grade group 1 and 2 tumors (P = 0.0051). In the standard cohort, more patients chose radiation over prostatectomy (47.2% vs. 24.4%, P<0.0001). On multivariate analysis, race was an independent predictor of active surveillance, with African Americans less likely to undergo active surveillance.Conclusions: Patients who undergo MRI/US targeted biopsy are more likely to choose active surveillance over early definitive treatment compared to men diagnosed on systematic biopsy when adjusting for tumor grade, PSA density, prior biopsy history, race, and provider. [ABSTRACT FROM AUTHOR]

Since its development between 1966 and 1977, the Gleason grading system has remained one of the most important prognostic indicators in prostatic acinar adenocarcinoma. The grading system was first majorly revised in 2005 and again in 2014. With the publication of the 8th edition of the American Joint Committee on Cancer TNM staging manual in 2018, the classification of prostate cancer and its reporting have further evolved and are now included as part of staging criteria. This article reflects the aspects that are most influential on daily practice. A brief summary of 3 ancillary commercially available genomic tests is also provided., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The risk of recurrence for prostatic adenocarcinoma after prostatectomy, as detected by prostate-specific antigen or other modalities, is based primarily on Gleason score along with pathologic tumor stage and surgical margin status. Recent large multi-institutional data spanning the last decade have supported modification of risk of recurrence stratification based on grade groups: grade group 1 (3+3=6), grade group 2 (3+4=7), grade group 3 (4+3=7), grade group 4 (4+4=8), and grade group 5 (Gleason scores 9 and 10). Using currently accepted grading definitions of grade patterns and grading rules, this study examines how the introduction of a limited, less than 5%, Gleason pattern 5 component at prostatectomy affects prognosis and fits into the grade group schema and reporting. The aggregate data from 2 independent major academic medical centers comprising 7606 patient records were analyzed with respect to biochemical recurrence-free survival. The presence of a limited (tertiary) Gleason pattern 5 component in the context of Gleason scores 3+4=7 (grade group 2) and 4+3=7 (grade group 3) imparts an intermediate prognosis relative to the next highest grade group. As such, we suggest that an additional comment and designation to the grade groups be provided reflecting the increased risk of recurrence in such cases (such as grade group 2+ or 3+). In contrast, the presence of limited (<5%) Gleason pattern 5 in the context of Gleason score 4+4=8 imparts a poor prognosis equivalent to grade group 5 and therefore should be reported as grade group 5., (Copyright © 2016 Elsevier Inc. All rights reserved.)