International Society of Urological Pathology (ISUP)-Grade Grouping in Prostatic Adenocarcinoma and its Prognostic Implications.

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.

Benefits and harms of the new prostate cancer grade grouping on the prediction of long-term oncological outcomes in patients after radical prostatectomy.

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.

A Deep Learning Pipeline for Grade Groups Classification Using Digitized Prostate Biopsy Specimens.

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.

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

OBJECTIVES: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. PATIENTS AND METHODS: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG ≥ 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. RESULTS: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%). CONCLUSION: The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.

Grade groups at diagnosis in African Caribbean men with prostate cancer: Results of a comparative study.

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.

Prostate cancer with comedonecrosis is frequently, but not exclusively, intraductal carcinoma: a need for reappraisal of grading criteria.

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.

Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study.

OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s. PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR. RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47). CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

[Multiparametric magnetic resonance imaging markers of clinically significant prostate cancer].

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.

Oncological outcomes in an Australian cohort according to the new prostate cancer grading groupings.

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.

Metastatic potential to regional lymph nodes with Gleason score ≤7, including tertiary pattern 5, at radical prostatectomy.

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.

Recent advances in prostate cancer pathology: Gleason grading and beyond.

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.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Intraductal Carcinoma of the Prostate versus Simulants: A Differential Diagnosis Growing in Clinical Impact.

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.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

Grade Group 1 Prostate Cancers Exhibit Tumor-defining Androgen Receptor-driven Programs.

Grade group 1 (GG1) primary prostate cancers with a pathologic Gleason score of 6 are considered indolent and generally not associated with fatal outcomes, so treatment is not indicated for most cases. These low-grade cancers have an overall negligible risk of locoregional progression and metastasis to distant organs, which is why there is an ongoing debate about whether these lesions should be reclassified as "noncancerous". However, the underlying molecular activity of key disease drivers, such as the androgen receptor (AR), have thus far not been thoroughly characterized in low-grade tumors. Therefore, we set out to delineate the AR chromatin-binding landscape in low-grade GG1 prostate cancers to gain insights into whether these AR-driven programs are actually tumor-specific or are normal prostate epithelium-like. These analyses showed that GG1 tumors do not harbor a distinct AR cistrome and, similar to higher-grade cancers, AR preferentially binds to tumor-defining cis-regulatory elements. Furthermore, the enhancer activity of these regions and the expression of their respective target genes were not significantly different in GG1 tumors. From an epigenetic perspective, this finding supports the cancer designation currently given to these low-grade tumors and clearly distinguishes them from noncancerous benign tissue. PATIENT SUMMARY: We characterized the molecular activity of the androgen receptor protein, which drives prostate cancer disease, in low-grade tumors. Our results show that these tumors are true cancers and are clearly separate from benign prostate tissue despite their low clinical aggressiveness.

Multi-Stage Classification-Based Deep Learning for Gleason System Grading Using Histopathological Images.

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.

Prostate Cancer: Update on Grading and Reporting.

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.

Correlation of Stiffness of Prostate Cancer Measured by Shear Wave Elastography with Grade Group: A Preliminary Study.

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.

Impact of Grade Groups on Prostate Cancer-Specific and Other-Cause Mortality: Competing Risk Analysis from a Large Single Institution Series.

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.