Fuhrman Grading Research Articles

Machine Learning-Enabled Fuhrman Grade in Clear-cell Renal Carcinoma Prediction Using Two-dimensional Ultrasound Images

ObjectiveAccurate assessment of Fuhrman grade is crucial for optimal clinical management and personalized treatment strategies in patients with clear cell renal cell carcinoma (CCRCC). In this study, we developed a predictive model using ultrasound (US) images to accurately predict the Fuhrman grade. MethodsBetween March 2013 and July 2023, a retrospective analysis was conducted on the US imaging and clinical data of 235 patients with pathologically confirmed CCRCC, including 67 with Fuhrman grades Ⅲ and Ⅳ. This study included 201 patients from Hospital A who were divided into training set (n = 161) and an internal validation set (n = 40) in an 8:2 ratio. Additionally, 34 patients from Hospital B were included for external validation. US images were delineated using ITK software, and radiomics features were extracted using PyRadiomics software. Subsequently, separate models for clinical factors, radiomics features, and their combinations were constructed. The model's performance was assessed by calculating the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). ResultsIn total, 235 patients diagnosed with CCRCC, comprising 168 low-grade and 67 high-grade tumors, were included in this study. A comparison of the predictive performances of different models revealed that the logistic regression model exhibited relatively good stability and robustness. The AUC of the combined model for the training, internal validation and external validation sets were 0.871, 0.785 and 0.826, respectively, which were higher than those of the clinical and imaging histology models. Furthermore, the calibration curve demonstrated excellent concordance between the predicted Fuhrman grade probability of CCRCC using the combined model and the observed values in both the training and validation sets. Additionally, within the threshold range of 0–0.93, the combined model demonstrated substantial clinical utility, as evidenced by DCA. ConclusionThe application of US radiomics techniques enabled objective prediction of Fuhrman grading in patients with CCRCC. Nevertheless, certain clinical indicators remain indispensable, underscoring the pressing need for their integrated use in clinical practice. Advances in knowledgePrevious studies have predominantly focused on using computed tomography or magnetic resonance imaging modalities to predict the Fuhrman grade of CCRCC. Our findings demonstrate that a prediction model based on US images is more cost-effective, easily accessible and exhibits commendable performance. Consequently, this study offers a promising approach to maximizing the use of US examinations in future research.

Nuclear morphological atypia in biopsy accurately reflects the prognosis of myxoid liposarcoma.

Currently, it is difficult to predict the prognosis of myxoid liposarcoma (MLS) in biopsy specimens. In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46years (interquartile range, 37 - 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses revealed a significantly worse disease-free survival in the high-grade group (hazard ratio (HR), 7.51; 95% confidence interval (CI), 2.67-21.1, p < 0.001 by the modified WHO/ISUP grading; HR, 4.45; 95% CI, 1.63-12.1, p = 0.001 by the modified Fuhrman grading). Moreover, the modified WHO/ISUP grade showed a significantly worse overall survival in the high-grade group (HR, 4.39; 95% CI, 1.04-18.6, p = 0.028), and the modified Fuhrman grade exhibited a similar, but not significant, trend. Our results indicate that nuclear morphology grading is a good predictor of patient prognosis at the time of biopsy in MLS. Even when cell density is sparse, treatment strategies should be carefully considered when individual tumor cells exhibit atypical nuclei.

Enhancing the Efficacy of Radiomics-Based Prediction of Fuhrman Pathological Grading in Renal Clear Cell Carcinoma Using Multilayer Spiral CT Imaging.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC). Conventional pathological methods of Fuhrman pathological grading system have limitations. This study aims to investigate the efficacy of radiomics-based multilayer spiral computed tomography (CT) imaging of Fuhrman pathological grading in ccRCC. A retrospective analysis was conducted on the clinical data of ccRCC patients admitted in our hospital from March 2023 to March 2024. The patients were classified as low-grade (Fuhrman pathological grades I and II) or high-grade (Fuhrman pathological grades III and IV). Statistical methods, including correlation analysis, receiver operating characteristic (ROC) curves and construction of a joint predictive model, were utilised to assess the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. The primary outcome assessment parameter in this study was the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. The clinical data from 101 ccRCC patients were examined, with 56 cases classified as low-grade and 45 cases as high-grade. The grey-level co-occurrence matrix (GLCM) features between low and high Fuhrman grading groups, including contrast (0.24 ± 0.08 vs. 0.33 ± 0.09), energy (0.73 ± 0.05 vs. 0.67 ± 0.06) and homogeneity (0.63 ± 0.05 vs. 0.57 ± 0.05), showed notable distinctions (p < 0.001). The CT imaging characteristics between low and high Fuhrman grading groups, including enhancement homogeneity (0.34 ± 0.08 vs. 0.26 ± 0.08) and washout half-time (28.57 ± 4.35 vs. 34.72 ± 5.62) demonstrated a substantial variation between the groups (p < 0.001). The enhancement homogeneity (r = 0.476), washout half-time (r = -0.519), contrast (r = 0.454), energy (r = -0.453) and homogeneity (r = -0.541) showed significant correlations with Fuhrman pathological grading. The predictive value of these features was evident, with a combined imaging genomics model exhibiting an area under the curve of 0.929. This study demonstrated the potential of radiomics-based prediction using multilayer spiral CT imaging for accurately predicting Fuhrman pathological grading in ccRCC.

A Weakly Supervised Deep Learning Model and Human-Machine Fusion for Accurate Grading of Renal Cell Carcinoma from Histopathology Slides.

(1) Background: The Fuhrman grading (FG) system is widely used in the management of clear cell renal cell carcinoma (ccRCC). However, it is affected by observer variability and irreproducibility in clinical practice. We aimed to use a deep learning multi-class model called SSL-CLAM to assist in diagnosing the FG status of ccRCC patients using digitized whole slide images (WSIs). (2) Methods: We recruited 504 eligible ccRCC patients from The Cancer Genome Atlas (TCGA) cohort and obtained 708 hematoxylin and eosin-stained WSIs for the development and internal validation of the SSL-CLAM model. Additionally, we obtained 445 WSIs from 188 ccRCC eligible patients in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort as an independent external validation set. A human-machine fusion approach was used to validate the added value of the SSL-CLAM model for pathologists. (3) Results: The SSL-CLAM model successfully diagnosed the five FG statuses (Grade-0, 1, 2, 3, and 4) of ccRCC, and achieved AUCs of 0.917 and 0.887 on the internal and external validation sets, respectively, outperforming a junior pathologist. For the normal/tumor classification (Grade-0, Grade-1/2/3/4) task, the SSL-CLAM model yielded AUCs close to 1 on both the internal and external validation sets. The SSL-CLAM model achieved a better performance for the two-tiered FG (Grade-0, Grade-1/2, and Grade-3/4) task, with AUCs of 0.936 and 0.915 on the internal and external validation sets, respectively. The human-machine diagnostic performance was superior to that of the SSL-CLAM model, showing promising prospects. In addition, the high-attention regions of the SSL-CLAM model showed that with an increasing FG status, the cell nuclei in the tumor region become larger, with irregular contours and increased cellular pleomorphism. (4) Conclusions: Our findings support the feasibility of using deep learning and human-machine fusion methods for FG classification on WSIs from ccRCC patients, which may assist pathologists in making diagnostic decisions.

Correlation Between Tumor-Associated Collagen Signature and Fibroblast Activation Protein Expression With Prognosis of Clear Cell Renal Cell Carcinoma Patient

Despite recent promising findings from immunotherapy and other targeted medicines, individuals with metastatic clear cell renal cell carcinoma (mCCRCC) still have a poor prognosis. Biomarkers associated with metastatic status in CCRCC are important for early detection and for the identification of new therapeutic targets. The expression of fibroblast activation protein (FAP) is associated with the development of early metastases and worse cancer-specific survival. Tumor-associated collagen signature (TACS) is a type of collagen that develops during tumor growth and is associated with tumor invasion.Twenty-six mCCRCC patients that underwent nephrectomy were admitted to this study. Data regarding age, sex, Fuhrman's grade, tumor diameter, staging, FAP expression, and TACS grading were collected. Spearman rho test was used to correlate FAP expression and TACS grading in both primary tumors and metastases and with the patient's age and sex.FAP manifestation correlated positively with TACS degree (Spearman rho test r = 0.51; P = 0.0001). FAP was positive in 25 (96%) of all intratumor samples and positive in 22 (84%) of all stromal samples.FAP can be used as a prognostic factor in mCCRCC; its presence can predict the aggressiveness of mCRCC and poorer outcome in the patient. Furthermore, TACS can also be used for the prediction of aggressiveness and metastasis due to the changes necessary for a tumor to invade other organs.

Characterization of renal artery variation in patients with clear cell renal cell carcinoma and the predictive value of accessory renal artery in pathological grading of renal cell carcinoma: a retrospective and observational study

ObjectiveTo explore the characteristics of renal artery variation in patients with renal cell carcinoma and to evaluate the predicting value of accessory renal artery in the pathological grading of renal cell carcinoma.MethodsThe clinicopathological data of patients with clear cell renal cell carcinoma diagnosed in the Department of Urology of the First Hospital of Shanxi Medical University from September 2019 to March 2023 were retrospectively analyzed. All patients underwent visual three-dimensional model reconstruction from computed tomography images. All kidneys were divided into two groups: the affected kidney and the healthy kidney, and the incidence of renal artery variation in the two groups was analyzed. Then, according to the existence of accessory renal artery in the affected kidney, the patients were divided into two groups, and the relationship between accessory renal artery and clinicopathological features of patients with clear cell renal cell carcinoma was analyzed. Finally, univariate and multivariate logistic regression analyses were performed to determine the predictors of Fuhrman grading of clear cell renal cell carcinoma, and the predictive ability of the model was evaluated by the receiver operating characteristic curve.ResultsThe incidence of renal artery variation and accessory renal artery in the affected kidney was significantly higher than them in the healthy kidney. The patients with accessory renal artery in the affected kidney had larger tumor maximum diameter, higher Fuhrman grade and more exophytic growth. The presence of accessory renal artery on the affected kidney and the maximum diameter of tumor are independent predictors of high-grade renal cell carcinoma. The receiver operating characteristic curve suggests that the model has a good predictive ability.ConclusionThe existence of accessory renal artery on the affected kidney may be related to the occurrence and development of clear cell renal cell carcinoma, and can better predict Fuhrman grade of clear cell renal cell carcinoma. The finding provides a reference for the future diagnostic evaluation of RCC, and provides a new direction for the study of the pathogenesis of RCC.

Histologic re‑evaluation of a population‑based series of renal cell carcinomas from The Netherlands Cohort Study according to the 2022 ISUP/WHO classification.

The aim of the present study was to re-evaluate 457 renal cell carcinoma (RCC) cases from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large population-based cohort, according to the new 2022 ISUP, Genitourinary Pathology Society and World Health Organisation (WHO) classifications to assess whether newly recognized subtypes of RCC could be found among these cases. These cases were initially evaluated according to the 2004 WHO classification, the Fuhrman grading system and the 3rd version of the Tumor-Node-Metastasis (TNM). Data on tumor size, laterality and date of diagnosis, among other clinicopathological characteristics, were obtained through record linkage with the Netherlands Cancer Registry and the Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief. Digital slides from the NLCS were reviewed by two urogenital pathologists according to the new ISUP grading and the 2022 WHO classification (5th edition). Immunohistochemistry staining for carbonic anhydrase IX was performed on cases with ambiguous morphology. A total of 373 cases of clear cell RCC (ccRCC), 61 cases of papillary RCC (pRCC), 13 cases of chromophobe RCC, 3 cases of collecting duct carcinoma and 4 cases of oncocytoma were identified. The subtyping showed no discrepancy with the previous diagnoses. A comparison of the WHO/ISUP grading to the original Fuhrman grading showed a similar grading in 245 (56.5%) cases of the total ccRCC and pRCC cases. The staging according to the novel TNM classification 8th edition showed a restaging in 286 cases (65.5%). Lymphovascular (microvascular) invasion (LVI) and tumor necrosis (TN) were present in 14.4% and 33.5% of the total number of cases, respectively. Furthermore, the presence of sarcomatoid differentiation in 5.1% and rhabdoid differentiation in 4.2% of the cases was observed. In conclusion, none of the newly accepted and emerging/provisional RCC entities were identified in the NLCS cases, which could be attributed to the high mean age (71.4 years) at diagnosis of the patients included in the present study. A restaging of the NLCS cases using the TNM 8th edition and regrading using ISUP grading was performed, which showed that it is possible to report on newer features, such as sarcomatoid differentiation and LVI, even in an old sample collection.

Prognostic value of nuclear morphometry in myxoid liposarcoma.

Myxoid liposarcoma (MLS) accounts for 20%-30% of liposarcoma and the round cell component (RCC) is believed to be a specific poor prognostic factor. However, the RCC assessment criteria are vaguely defined and, therefore, are inconsistently employed by pathologists. In this study, we modified and applied two established grading systems to evaluate nuclear atypia (namely, the World Health Organization/International Society of Urological Pathology and the Fuhrman grading in renal cell carcinoma) in 64 MLS cases. Detailed software-based assessments of the morphology and the cellularity were performed. DNA mutation analysis, comprehensive mRNA expression analysis, and immunohistochemistry were also performed. Our findings revealed that the high-nuclear-grade group according to the modified Fuhrman grading system exhibited a significantly poor disease-free survival (hazard ratio: 4.43; 95% confidence interval: 0.9-22.6; p=0.047). On the other hand, the cellularity was significantly higher in the modified Fuhrman high-grade group (p=0.010 at the percentage of the hypercellular area; p=0.003 at the maximum cell density) but did not qualify per se as a poor prognostic factor in the survival analyses. Furthermore, the modified Fuhrman high-grade group significantly expressed the cell cycle-related genes (such as FOXM1, PLK1, and CDK1). In conclusion, our analyses suggest that an evaluation focusing on nuclear morphology (rather than on cellular density) can be more reliable in predicting the MLS prognosis.

Radical Nephrectomy for Renal Cell Carcinoma in a Tertiary Care Hospital in Islamabad

Objective: to identify the demographic, laboratory, radiological and histological features of RCC patients presenting to a tertiary care hospital in Islamabad.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Pakistan Atomic Energy Commission General Hospital, Islamabad Pakistan, from Jan 2014 to Aug 2021.&#x0D; Methodology: All the patients who underwent radical nephrectomy for histologically confirmed RCC at PAEC General Hospital Islamabad were included in the study. Demographic variables, ultrasound features, laboratory measures, histological types and Fuhrman grading were noted.&#x0D; Results: A total of 65 consecutive patients were included, which included 38(58.5%) males. The mean age of the patients was 52.6±8.6 years. The most common symptom was flank pain (42.2%). The diagnosis was made incidentally in 26 patients. The most common ultrasound feature was capsule involvement (23, 35.3%), and most cases were Fuhrman Grade-II (22, 48.9%). On histology, clear cell carcinoma was the most common RCC (40, 61.5%). Post-operative early RFT deterioration was noted in 32(49.2%) patients. This was significantly associated with greater tumour size, Fuhrman Grade-III/IV, renal vein thrombosis, gerota fascia, and ureteric involvement. There was no mortality in our study during the admission days until discharge.&#x0D; Conclusion: Renal cell carcinoma was more common among males and at a later stage of life (5th decade). The most common type was clear cell carcinoma. Post-operative early RFT deterioration was noted in 49.2% of patients. It was associated with greater tumour size, Fuhrman Grade III and IV, renal vein thrombosis, gerota fascia, and ureteric involvement.

Predictors of local recurrence of renal cell cancer. Our experience

Risk factors for renal cell cancer (RCC) recurrence, including its local form, include stage and high Fuhrman grading system score, regional lymph node involvement, microvascular invasion, tumor necrosis, positive surgical margin, and sarcomatoid or rhabdoid tumor differentiation. Objective. The study analyzes data from Moscow Research Oncological Institute named by PA Herzen to determine the predictors of local recurrence of kidney cancer based on the data from surgically treated patients with local recurrent RCC. Material and methods. We analyzed retrospectively data from 87 patients who were divided into 2 groups: 1-st, patients with detected local recurrence of kidney cancer (n=43), and 2-nd, control group (n=44). The following predictors were evaluated: tumor size, tumor histotype, tumor stage, Fuhrman grading system, surgical margin status, tumor necrosis, sarcomatoid and rhabdoid changes, microvascular invasion, hemorrhage and invasion of collecting system components (CSS), renal capsule, and perirenal cellular tissue and primary treatment. Results. The risk of local recurrence was higher in the primary tumor, over 40 mm in diameter (OR=5.8, p&lt;0.001), as well as microvascular invasion and focal hemorrhage (OR=15.1, p=0.001 and OR=3.3, p=0.008, respectively). Both univariate and multivariate analyses showed a negative effect on the risk of local RCC recurrence only for tumor necrosis (OR=15.4, p&lt;0.001 and OR=53.6, p=0.002, respectively) and high Fuhrman grade (OR=10.9, p=0.042 and OR=5.7, p=0.032, respectively). The most significant predictors of local renal cancer recurrence are tumor necrosis (p&lt;0.001), microvascular invasion (p=0.019), positive surgical margin (p=0.009), and high Fuhrman grade (p=0.04). High Fuhrman grade (3–4) of malignancy (HR=1.9, p=0.042), tumor diameter (HR=1.0, p=0.054), positive surgical margin (HR=3.5, p=0.001), and tumor necrosis (HR=2.3, p=0.029) were found to be the most significant factors influencing 5-year local recurrence-free survival rate. Conclusion. The course of renal cell cancer is determined by multiple interrelated and independent prognostic factors.

MO165: The Controversial Role of Proteinuria and Urinary Output After Radical Nephrectomy in the Development Of Acute Kidney Injury: Double Agents

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is increasingly common and associated with adverse short- and long-term outcomes in oncological patients who require radical nephrectomy (RN) for the presence of renal cancer. As defined by the KDIGO Criteria classification system, the diagnosis of AKI is nowadays based on changes in the serum creatinine levels (sCr) or urine output. However, these parameters often underestimate the severity of renal damage and therefore recent insights have resulted in the implementation of proteinuria as means of more accurately assessing for AKI. Proteinuria represents indeed an indicator of both glomerular and renal endothelial injury in chronic disease (CKD), whereas in AKI the presence of proteinuria could be derived from a tubular dysfunction. In the RN scenario, it is still debatable if the development of a mild to severe proteinuria after surgery could be considered a marker of renal damage resulting in AKI or, on the opposite, could be a physiological sign of adaptive compensatory hyperfiltration promoted by the remanent counterlateral kidney. The aim of our study was to investigate if the development of a postoperative proteinuria plays a positive or negative role in the prevention of AKI in a consecutive cohort of nephrectomized patients affected by renal cancer. METHOD We enrolled a consecutive cohort of 131 patients who underwent RN due to the presence of a kidney mass suspected of malignancy from 2018 to 2021 in a tertiary care urological Institution. The following data were considered: age, gender, body mass index (BMI), smoke, TNM staging, Fuhrman grading, hypertension, diabetes, cardiovascular events, dyslipidaemia, medical therapy (ACE-inhibitors (ACEi), angiotensin II receptor blockers (ARBs), calcium antagonists, beta blockers and diuretics), proteinuria in 24 h, urine volume in 24 h, preoperative haematocrit and haemoglobin. Serum creatinine (s-Cr) values [Kinetic Picrate standardized (COBAS C 800) for IDMS] were collected before surgery (t 0) and at 24, 48 and 72 h after surgery and at dismissal (respectively t 1, t 2 and tf) to detect renal function fluctuations and the subsequent risk of AKI. GFR was estimated at baseline using CKD-EPI 2012 and MDRD formula. The level of proteinuria was measured at 24 h postoperative and was standardized on the urine volume. Each operated patient underwent the same pre-peri- and postoperative medical protocol in terms of surgical and anesthesiologic management. Patients affected by pre-existing medical nephropathies with proteinuria were excluded. Comparisons between groups were performed using the Kruskal–Wallis rank sum test for numerical variables and Pearson's Chi-squared test for categorical variables. Logistic regression was used to identify variables odds ratio for AKI onset after surgery. RESULTS Descriptive analysis is shown in Table 1. Our analysis surprisingly underlined that 66% of overall patients experienced AKI after surgery. Moreover, the analysis showed a significant difference (P value &amp;lt; .05) between the AKI cohort and the non-AKI group concerning basal serum creatinine (sCr), eGFR using both CKD-EPI and MDRD and postoperative urine volume. In particular, the lower the basal sCr or eGFR, the higher was the risk of developing AKI. Concerning the urine output, the median volume of AKI population was significantly less in respect to their counterpart, but far from the critical definition of oliguria or anuria (Table 1 and Figure 1). On the contrary, no evidence related to a possible prognostic role of proteinuria was underlined. CONCLUSION Our work underlined that proteinuria does not represent a valid biomarker for AKI development after RN. On the contrary, basal eGFR, serum creatinine and postoperative urinary volume could be promising tools to predict and follow the acute renal damage after RN.

Prognostic role of hematologic parameters of metastatic renal cell carcinoma treated with sunitinib.

Hemochrome parameters at the diagnosis of metastatic renal cell carcinoma (mRCC) and the development of macrocytosis during sunitinib therapy are considered prognostic. To evaluate the prognostic role of hematologic parameters and macrocytosis in mRCC treated with sunitinib. We analyzed clinical data of 100 patients with mRCC treated with sunitinib as first-line therapy in a retrospective multicenter study. We calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) at baseline and erythrocyte mean corpuscular volume (MCV) during therapy. We considered the following cutoffs: NLR >3, PLR >150, LMR <3, and MCV >100 fl. Clinical data histology, prior nephrectomy, Fuhrman grading, metastatic sites, Memorial Sloan-Kettering Cancer Center score, and Heng score were collected. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariate and multivariate analysis using Cox regression model with time-dependent (macrocytosis) covariate were applied. At the univariate analysis, low LMR was associated with shorter PFS and OS (p = 0.02 and p = 0.06, respectively). High PLR was associated with worse PFS (p = 0.005); median OS was 23 vs 28 months (p = 0.13). At the multivariate analysis, poor risk (Heng score), low LMR, and high PLR were associated with shorter PFS (hazard ratio 7.1, 1.5, and 2, respectively); poor PS and poor risk (Heng score) were related to worst OS. Macrocytosis was observed in 26 patients and was not prognostic of survival. In our cohort of patients with mRCC treated with sunitinib, low LMR (>3) and high PLR (>150) were associated with shorter PFS. Macrocytosis was not prognostic.

Comparing World Health Organization/International Society of Urological Pathology Grading and Fuhrman Grading with the Prognostic Value of Nuclear Area in Patients with Renal Cell Carcinoma

This study was undertaken to compare Fuhrman grading with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading and stereologically measured nuclear area in patients with Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (PRCC) and to evaluate the independent predictive value of Fuhrman, WHO/ISUP and stereologically measured nuclear area combined with necrosis in a series of patients with ccRCC in relation to cancer-specific survival. In all, 124 cases of ccRCC and PRCC were included. All slides were blindly scored by two trained pathologists according to the Fuhrman and WHO/ISUP grading systems. Nuclear measurements were performed on digitally scanned slides in Visiopharm® and correlated to survival. Analysis of ccRCC and PRCC cases showed that application of WHO/ISUP grading resulted in a significant downgrading of cases from G2 to G1, when comparing with Fuhrman grading. Neither of these patients experienced progression. Cancer specific survival estimates in 101 ccRCC patients showed that WHO/ISUP grading was slightly superior in predicting cancer-specific survival. Novel models included WHO/ISUP grading and mean nuclear area (MNA) each of which combined with necrosis. Both demonstrated an increased ability to predict cancer-specific survival. The study demonstrates that WHO/ISUP grading provides superior prognostic information compared to Fuhrman grading and stereologically measured nuclear area. Necrosis in combination with either WHO/ISUP grading or MNA adds additional prognostic information.

Validation of the World Health Organization/International Society of Urological Pathology grading for Chinese patients with clear cell renal cell carcinoma.

BackgroundThis study aimed to compare the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system and the Fuhrman grading system and to verify the WHO/ISUP grade as a prognostic parameter of clear cell renal cell carcinoma (ccRCC) in a Chinese population.MethodsThe study consisted of 753 ccRCC patients treated with curative surgery between 2010 and 2018 at Xiangya Hospital Central South University (Changsha, China). All pathologic data were retrospectively reviewed by two pathologists. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were examined as clinical outcomes.ResultsAccording to the WHO/ISUP grading system (ISUP group), nephrectomy type, pT stage and WHO/ISUP grade were independent risk factors for CSS (P<0.0001, P=0.0127 and P<0.0001, respectively) and RFS (P<0.0001, P=0.0077, and P<0.0001, respectively). In the Fuhrman group, nephrectomy type, pT stage and Fuhrman grade were independent risk factors for CSS (P<0.0001, P=0.0004, and P<0.0001, respectively) and RFS (P<0.0001, P=0.0001, and P<0.0001, respectively). The C-index for CSS and RFS using the Fuhrman grading system was 0.6323 and 0.6342, respectively, and that using the WHO/ISUP grading system was 0.6983 and 0.7005, respectively, both higher than the former (P=0.0185, and P=0.0172, respectively). In addition, upgrading from Fuhrman grade 2 to ISUP grade 3 resulted in worse CSS and RFS for ccRCC patients (P=0.0033 and P =0.0003, respectively).ConclusionsWe first verified correlations between the postoperative prognosis and WHO/ISUP grade of ccRCC in a Chinese population and confirmed that the ability to predict clinical outcomes with the WHO/ISUP grading system was superior to that with the Fuhrman grading system.

Interobserver Variability in Assessment of Renal Mass Biopsies.

The main goal of this study was to assess the histopathological efficacy of renal mass biopsy and to check the concordance between pathological results and biopsy of the final specimen, as well as interobserver variability in the assessment of biopsy cores. A hundred sets of core biopsies of postoperative specimens (renal masses) have been performed. Three core biopsies of the intact specimen had been performed once the kidney with the tumor, or the tumor alone were resected. The urologist aimed to obtain two cores from the peripheral sides of the tumor and one core from its center. The surgical specimen was evaluated by a single pathologist, whereas biopsy samples were referred to three independent pathologists who were blinded to the final results of the renal mass biopsy. Nondiagnostic biopsy rates ranged from 13% to 22%. Sensitivity and specificity ranged 83-97% and 97-99% by excluding nondiagnostic results. The concordance between assessment of surgical specimen and biopsy in the Fuhrman grading system ranged 36.5-77.0%, respectively. Interobserver agreement between the three pathologists was substantial or moderate, depending on the tumor subtype. The Krippendorff's alpha coefficient, calculated by excluding the nondiagnostic results, was 0.28 (moderate agreement) for the Fuhrman grading system. The agreementregarding grading of biopsies between threepathologists ranged from moderate to substantial.Therefore, a team ofdedicated uropathologists should be engaged in final diagnosis of renal mass biopsy rather than single one before implementing the proper treatment.

Serum and tissue syndecan-1 levels in renal cell carcinoma.

BackgroundThe proteoglycan syndecan-1 is involved in cell proliferation, adhesion and angiogenesis. It was shown to be involved in cancer progression in different tumor entities. So far, the role of syndecan-1 in renal cell carcinoma (RCC), one of the most common diseases in urologic oncology, was little described. Purpose of the present study was to obtain serum concentrations and tissue expression levels of syndecan-1 in a cohort of patients diagnosed with RCC.MethodsClinical and follow-up data were obtained from 413 RCC patients. SDC1 levels were determined in serum samples of 100 patients by enzyme-linked immunosorbent assay and tissue SDC1 expression was measured by immunohistochemistry (IHC) in 343 cases. Results were correlated with clinicopathological and follow-up data.ResultsFive and ten years overall and cancer specific survival were 67% and 56% [overall survival (OS)] and 79% and 76% [cancer-specific survival (CSS)]. In female patients and locally advanced disease (≥T3), tissue SDC1 expression was decreased (female 85.6% vs. male 71.1% low tissue SDC1 expression, P=0.0153 and ≤T2 70.0% vs. ≥T3 87.2% low tissue SDC1 expression, P=0.0055) compared to male patients and organ confined disease. Locally advanced tumor stage, presence of lymph node or distant metastases, high Fuhrman grading and clear cell carcinoma as histopathological subtype were independent prognostic factors for reduced CSS and OS. There was no impact of serum SDC1 (sSDC1) serum concentration or SDC1 tissue protein expression on OS, CSS or recurrence free survival (RFS) in uni- or multivariable analysis.ConclusionssSDC1 concentration or SDC1 tissue protein expression levels had no influence on patients’ prognosis in the present cohort of patients diagnosed with RCC.

Noninvasive Fuhrman grading of clear cell renal cell carcinoma using computed tomography radiomic features and machine learning.

To identify optimal classification methods for computed tomography (CT) radiomics-based preoperative prediction of clear cell renal cell carcinoma (ccRCC) grade. Seventy-one ccRCC patients (31 low grade and 40 high grade) were included in this study. Tumors were manually segmented on CT images followed by the application of three image preprocessing techniques (Laplacian of Gaussian, wavelet filter, and discretization of the intensity values) on delineated tumor volumes. Overall, 2530 radiomics features (tumor shape and size, intensity statistics, and texture) were extracted from each segmented tumor volume. Univariate analysis was performed to assess the association between each feature and the histological condition. Multivariate analysis involved the use of machine learning (ML) algorithms and the following three feature selection algorithms: the least absolute shrinkage and selection operator, Student's t test, and minimum Redundancy Maximum Relevance. These selected features were then used to construct three classification models (SVM, random forest, and logistic regression) to discriminate high from low-grade ccRCC at nephrectomy. Lastly, multivariate model performance was evaluated on the bootstrapped validation cohort using the area under the receiver operating characteristic curve (AUC) metric. The univariate analysis demonstrated that among the different image sets, 128 bin-discretized images have statistically significant different texture parameters with a mean AUC of 0.74 ± 3 (q value < 0.05). The three ML-based classifiers showed proficient discrimination between high and low-grade ccRCC. The AUC was 0.78 for logistic regression, 0.62 for random forest, and 0.83 for the SVM model, respectively. CT radiomic features can be considered as a useful and promising noninvasive methodology for preoperative evaluation of ccRCC Fuhrman grades.

3:27 PM Abstract No. 267 Efficacy of percutaneous image-guided thermal ablation for renal cell carcinoma following ipsilateral partial nephrectomy

To evaluate the local efficacy of image-guided thermal ablation of renal cell carcinoma (RCC) after ipsilateral partial nephrectomy. We reviewed our institutional database for patients who underwent renal ablation for local recurrence in the ipsilateral kidney following partial nephrectomy between January 2005 and March 2019. We described demographics, tumor size, procedure details, complications, pathology and local oncologic outcome. Out of 710 renal ablations during the study period, a total of 35 patients (21 Males and 14 females) with a median age of 66 years met our inclusion criteria. Fifteen patients had a solitary kidney. Forty six procedures were performed for 52 lesions with average size of 2.3 cm (range, 0.8 – 4.5 cm). Four lesions were at the surgical margin. Pathology report revealed negative tumor margin in 3 patients, the fourth patient had surgery at another institution with no pathology report available. Of the 46 procedures, 42 were performed under CT and 4 were performed under MRI guidance. Of the 52 lesions, 43 were treated with RFA and 9 were treated with cryoablation. Technical success was obtained in all cases. Adjunctive Techniques; hydrodissection and pyeloperfusion were performed in 13 and 2 cases respectively. Four patients (11.5%) developed Clavien grade III complications. Of the 40 biopsied lesions, 36 samples were diagnostic (21 clear cell, 14 papillary, 1 hemangioma). Fuhrman grading was obtained in 29 lesions (grade 1 = 3, grade II = 22, grade III = 4). Median follow-up imaging was 4 years (0.5 – 11.5 years). Three lesions (5.7%) had residual/recurrence at the ablation site detected at 5.7, 6.6 and 7.3 months after ablation Thermal ablation is effective in treatment for RCC following ipsilateral partial nephrectomy. Long-term follow-up imaging reveals adequate local control in those patients.

Automated clear cell renal carcinoma grade classification with prognostic significance.

We developed an automated 2-tiered Fuhrman’s grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n = 72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman’s grades between TCGA and Pathologist 1 (training set n = 235; held-out test set n = 42). Discordant cases (n = 118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n = 160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21–3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts.

Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications

Renal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological cancers, which results in response to combination of genetic and epigenetic factors. Histone methylations have been implicated in renal tumorigenesis but their clinical significance and underlying pathology are unexplored. Here, we elucidated the histone 3 lysine 4 (H3K4) methylation patterns in clear cell RCC and its underlying pathology. Lower cellular levels of H3K4 mono-methylation, -dimethylation and –tri-methylation were fraternized with higher TNM staging and Fuhrman grading as well as tumor metastasis. Further, the expression profile of 20 H3K4 modifiers revealed the significant over-expression of histone demethylases compared to methyltransferases, indicating their role in the reduction of H3K4 methylation levels. In view of above facts, the role of LSD2 and KDM5A demethylases in RCC pathogenesis were explored using respective siRNAs. The RCC cells exhibited reduced cell viability after knockdown of LSD2 and KDM5A genes with concomitant induction of apoptosis. In addition, propidium iodide staining demonstrated an arrest of RCC cells at S-phase and sub-G1 phase of the cell cycle. Taken together, these observations provide new pathological insights behind the alterations of H3K4 methylation patterns in ccRCC with their prognostic and therapeutic implications.