Grade Of Renal Cell Carcinoma Research Articles

8126 PTH-Independent, Calcitriol-Mediated Hypercalcemia In Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

8126 PTH-independent, Calcitriol-mediated Hypercalcemia in Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

Abstract A059: Racial and ethnic variation in obesity rates and body composition and their associations with renal cell carcinoma grade, stage, and histologic subtype

Abstract Background: Obesity is more prevalent in minoritized groups, including Hispanics, American Indian (AI), and non-Hispanic Black (NHB), and these groups have higher renal cell carcinoma (RCC) incidence and mortality rates than non-Hispanic White (NHW). However, the role of abdominal adiposity in RCC disparities are still unknown. To address this gap, we investigated body composition variation and associations with RCC pathological characteristics accounting for neighborhood characteristics. Methods: Social vulnerability index (SVI) scores were linked to the zip code of patient’s residence. Preoperative CT and MRI scans were obtained. SliceOmatic software was used to measure intermuscular, visceral, and subcutaneous adipose tissue and skeletal muscle areas and were normalized for height to obtain intermuscular, visceral, and subcutaneous adipose tissue index (IMATI, VATI, and SATI) and skeletal muscle index (SMI). Non-parametric tests were used to examine correlations, and logistic regression analyses were performed to obtain odds ratio (OR) and confidence interval (CI). Results: A total of 235 patients, including 70 (29.8%) Hispanic, 17 (7.2%) AI, and 20 (8.5%) NHB, were included. Obesity was more common in Hispanic (58.6%), AI (70.6%), and NHB (60.0%) than NHW (47.9%) patients. Compared to NHW patients, SATI was higher in Hispanic (P<0.001) and AI (P=0.002), and VATI was higher in Hispanic patients (P=0.04). Patients from minoritized racial and ethnic groups were more likely to come from neighborhoods with high SVI. SVI was significantly positively correlated with BMI (P=0.02) and SATI (P<0.001). Among SVI themes, socioeconomic, housing and transportation, and minority and language characteristics were significantly positively correlated with SATI (P<0.01). All body composition measurements were significantly positively correlate with BMI (P<0.001). Patients from minoritized racial and ethnic groups were also more likely to have hypertension and diabetes, and patients with both conditions had higher BMI (P=0.002), IMATI (P<0.001), VATI (P<0.001), and SATI (P=0.01) than patients without either condition. Obesity was associated with reduced odds of high grade RCC (OR 0.53, 95% CI 0.29-0.93). After including comorbidities in the model, association was no longer significant. In the same model, AI patients showed a trend for increased odds of high grade (OR 3.28, 95% CI 0.85-12.62, P=0.08) compared to NHW patients. AI patients also had significantly increased odds of having advanced stage RCC (OR 3.72, 95% CI 1.14-12.19). The highest quartile of IMATI significantly increased odds of advanced stage (OR 4.53, 95% CI 1.43-14.36) and clear cell subtype (OR 5.87, 95% CI 1.17-29.55) compared to the lowest quartile with significant P for trend (0.009 and 0.03 respectively). The third quartile of VATI was also significantly associated with clear cell subtype (OR 13.27, 95% CI 13.27). Conclusion: Obesity rates and body composition vary among racially and ethnically diverse RCC patients and are associated with RCC pathological characteristics. Citation Format: Ken Batai, Juan Adrover Claudio, Robert M. Blew, Benjamin R. Lee, Hina Arif Tiwari, Patrick Wightman, Qian Liu, Charles L. Roche, Evan W Davis, Rikki Cannioto, Eric C. Kauffman, Jennifer W. Bea. Racial and ethnic variation in obesity rates and body composition and their associations with renal cell carcinoma grade, stage, and histologic subtype [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A059.

Histomorphological Study of Nephrectomy Specimens with Assessment of Prognostic Parameters in Renal Cell Carcinoma

Abstract Background: Kidney is a major organ that is affected by vast spectrum of non-neoplastic (NN) and neoplastic lesions. Simple nephrectomy is done for nonfunctioning kidneys in inflammatory/ benign disorders, radical / partial nephrectomy is done for neoplasms. Aims: This study aims to study the different histomorphological features observed in nephrectomy specimens and to assess the significance of prognostic parameters in the evaluation of renal cancers. Materials and Methods: This is a retrospective study that includes 71 nephrectomy specimens received in our department. Results: Among the 71 nephrectomy specimens 57.7% were NN lesions. Chronic pyelonephritis and Clear cell type of renal cell carcinoma (RCC) were the commonest NN and neoplastic lesions respectively. Majority of RCCs were histologically grade 2 (50%). A significant correlation was found between tumor size and grade, tumor size and renal sinus invasion (RSI) and RSI was frequently seen in higher grade RCCs. However, a larger sample size is needed to generalize these results. Conclusion: With early interventions of NN lesions and detecting RCC in early stages the need for surgical management and radical procedures can be brought down to spare this vital organ.

Adjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma

Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant. To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC. This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022. The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo. The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS. Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo. In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out. ClinicalTrials.gov Identifier: NCT01120249.

A novel convolution transformer-based network for histopathology-image classification using adaptive convolution and dynamic attention

Renal cell carcinoma (RCC), which is the primary subtype of kidney cancer, is among the leading causes of cancer. Recent breakthroughs in computer vision, particularly deep learning, have revolutionized the analysis of histopathology images, thus providing potential solutions for tasks such as the grading of renal cell carcinoma. Nevertheless, the multitude of available neural network architectures and the absence of systematic evaluations render it challenging to identify optimal models and training configurations for distinct histopathology classification tasks. Hence, we propose a novel hybrid model that effectively combines the advantages of vision transformers and convolutional neural networks. The proposed method, which is named the renal cancer grading network, comprises two essential components: an adaptive convolution (AC) block and a dynamic attention (DA) block. The AC block emphasizes efficient feature extraction and spatial representation learning via intelligently designed convolutional operations. The DA block, which is constructed on the features of the AC block, is a crucial module for histopathology-image classification. It introduces a dynamic attention mechanism and employs a transformer encoder to refine learned representations. Experiments were conducted on four publicly available histopathology datasets: RCC dataset of Kasturba medical college (KMC), colorectal cancer histology (CRCH), break cancer histology (BreakHis) and colon cancer histopathology dataset (CCH). The proposed method demonstrated an accuracy of 90.62%, precision of 91.23%, recall of 90.63%, and a weighted harmonic mean of precision and recall (F1-score) of 90.92 on the KMC dataset. Similarly, the proposed method demonstrates consistent accuracy (weighted average F1-score of 99%) on the CRCH dataset, recognition rate of 88.30% on the BreakHis dataset, and an accuracy of 99.7% on CCH dataset. These results confirm that our method outperforms the state-of-the-art methods, thus demonstrating its effectiveness and robustness across various datasets.

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU

IntroductionThe incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. Material and methodsWe conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. ResultsStudies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately −5 to −17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. ConclusionStereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. Level of evidence5.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55months [32.8-107.2] vs. 20months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9years (95% CI 3.3-not reached) for LC and a 3.8years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5years (95% CI 4.4-not reached) for LC and 6years (95% CI 4.3-11.6) for RCCM + . Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.

Frequency of Androgen Receptor Positivity in Tumors: A Study Evaluating More Than 18,000 Tumors.

Androgen receptor (AR) is a transcription factor expressed in various normal tissues and is a therapeutic target for prostate and possibly other cancers. A TMA containing 18,234 samples from 141 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. AR positivity was found in 116 tumor types including 66 tumor types (46.8%) with ≥1 strongly positive tumor. Moderate/strong AR positivity was detected in testicular sex cord-stromal tumors (93.3-100%) and neoplasms of the prostate (79.3-98.7%), breast (25.0-75.5%), other gynecological tumors (0.9-100%), kidney (5.0-44.1%), and urinary bladder (5.4-24.2%). Low AR staining was associated with advanced tumor stage (pTa versus pT2-4; p < 0.0001) in urothelial carcinoma; advanced pT (p < 0.0001), high tumor grade (p < 0.0001), nodal metastasis (p < 0.0001), and reduced survival (p = 0.0024) in invasive breast carcinoma; high pT (p < 0.0001) and grade (p < 0.0001) in clear cell renal cell carcinoma (RCC); and high pT (p = 0.0055) as well as high grade (p < 0.05) in papillary RCC. AR staining was unrelated to histopathological/clinical features in 157 endometrial carcinomas and in 221 ovarian carcinomas. Our data suggest a limited role of AR immunohistochemistry for tumor distinction and a prognostic role in breast and clear cell RCC and highlight tumor entities that might benefit from AR-targeted therapy.

To characterize small renal cell carcinoma using diffusion relaxation correlation spectroscopic imaging and apparent diffusion coefficient based histogram analysis: a preliminary study.

To study the capability of diffusion-relaxation correlation spectroscopic imaging (DR-CSI) on subtype classification and grade differentiation for small renal cell carcinoma (RCC). Histogram analysis for apparent diffusion coefficient (ADC) was studied for comparison. A total of 61 patients with small RCC (< 4 cm) were included in the retrospective study. MRI data were reviewed, including a multi-b (0-1500 s/mm2) multi-TE (51-200 ms) diffusion weighted imaging (DWI) sequence. Region of interest (ROI) was delineated manually on DWI to include solid tumor. For each patient, a D-T2 spectrum was fitted and segmented into 5 compartments, and the volume fractions VA, VB, VC, VD, VE were obtained. ADC mapping was calculated, and histogram parameters ADC 90th, 10th, median, standard deviation, skewness and kurtosis were obtained. All MRI metrices were compared between clear cell RCC (ccRCC) and non-ccRCC group, and between high-grade and low-grade group. Receiver operator curve analysis was used to assess the corresponding diagnostic performance. Significantly higher ADC 90th, ADC 10th and ADC median, and significantly lower DR-CSI VB was found for ccRCC compared to non-ccRCC. Significantly lower ADC 90th, ADC median and significantly higher VB was found for high-grade RCC compared to low-grade. For identifying ccRCC from non-ccRCC, VB showed the highest area under curve (AUC, 0.861) and specificity (0.882). For differentiating high- from low-grade, ADC 90th showed the highest AUC (0.726) and specificity (0.786), while VB also displayed a moderate AUC (0.715). DR-CSI may offer improved accuracy in subtype identification for small RCC, while do not show better performance for small RCC grading compared to ADC histogram.

Can We Predict the Grade of Clear Cell Renal Cell Carcinoma from Houns-Field Unit of Renal Lesion on Computerized Tomography Scan, a Retrospective Cross-Sectional Study.

Renal cell carcinoma (RCC) is a type of urological malignancy that affects approximately 2% of the global population. Imaging modalities, especially computed tomography (CT) scanning, play a critical role in diagnosing RCC. In this study, we investigated whether there is a relationship between tumour grade of clear cell RCC and HU values of renal lesions on CT scan performed before operation. We conducted a retrospective analysis of 123 patients who underwent radical or partial (open or laparoscopic) nephrectomy for clear cell RCC between January 2017 and January 2021. Post-operation histopathological grades were recorded according to World Health Organization (WHO)/International Society of Urological Pathology (ISUP) 2016 grading system and divided into low grade (includes grade 1 and 2) and high grade (grade 3 and 4), and their links to age, sex, smoking habits, tumour size, and HUs of renal lesions were evaluated. The mean age of the patients studied was 63.02 years old. About 56.9% of the patients were low grade (grade 1 or grade 2), while 43.1% were high grade (grade 3 or 4). The mean tumour size was 6.31 cm. There were no significant differences in tumour grade according to age, sex, or smoking habits. We found a significant relation between tumour grade and HU in the pre-contrast and nephrogenic phases, with p values of 0.001 and 0.037, respectively. On the other hand, there was no significant relation linking the tumour grade to the difference in HU between these phases, where there was a p value of 0.641. HU in the pre-contrast and nephrogenic phases in addition to tumour size on CT scan have a significant relation to clear cell RCC grade.

Abstract 1056: Development of a B-cell epitope classifier for early detection of renal cell carcinoma

Abstract A blood biomarker for early detection of renal cell carcinoma (RCC) would help decrease the burden of 15,000 deaths annually in the U.S. (1). Antibodies against tumor (neo)antigens are thought to arise early in cancer development and might serve as a more sensitive biomarker for RCC than tumor-derived biomolecules. Serum Epitope Repertoire Analysis (SERA) of human serum/plasma uses a random bacterial peptide display library and next generation sequencing to allow for unbiased highly multiplexed profiling of B cell epitopes. In combination with bioinformatic methods and machine learning, a classifier was trained to predict the presence of RCC using a cohort of 163 treatment-naïve patients (median age 62, stage: I 35%, II 5%, III 20%, IV 40%) with clear cell RCC (ccRCC) and 438 age-matched healthy controls (median age 61). Classifier performance was evaluated by sensitivity, specificity, and receiver operator curve (ROC) area under the curve (AUC) analysis in an independent validation cohort of 43 treatment-naïve patients with ccRCC (age 22-86, median 63, stage: I 33%, II 2%, III 26%, IV 39%) and 1,759 healthy controls (age 18-89, median 40). A total of 1,465 individual B cell epitope features were discovered and enriched in ccRCC vs. controls and included in a random forest model. In the validation cohort, the ROC-AUC was 0.65, and sensitivities of 9%, 16%, 30%, and 36% were achieved at specificities of 99%, 98%, 95%, and 90%, respectively. Performance was better in both early stage ccRCC and low tumor grade (grade 1 or 2). For stage I, the ROC-AUC was 0.88, and sensitivities of 7%, 14%, 36%, and 57% were achieved at specificities of 99%, 98%, 95%, and 90%, respectively. For low tumor grade, the ROC-AUC was 0.86, and sensitivities of 10%, 20%, 50%, and 60% of were achieved at specificities of 99%, 98%, 95%, and 90%, respectively. The classifier did not miscategorize benign renal lesions as ccRCC (Mann-Whitney p-value 0.52, ROC-AUC 0.54) in a separate cohort of 23 patients with benign renal tumors vs. the 1,759 healthy controls. This preliminary performance for a B cell epitope-based classifier is promising: the better performance in early stage ccRCC suggests that B cell epitope biomarkers may complement the lower sensitivity of cell-free DNA for detecting early-stage cancer (2). Future work will further validate these results in larger multi-institutional cohorts to improve classification performance and explore if B cell epitope biomarkers can be combined with existing assays to develop an early detection composite biomarker for RCC and tumor grade. (1)Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48.(2)Francini, E.; Fanelli, G.N.; Pederzoli, F.; Spisak, S.; Minonne, E.; Raffo, M.; Pakula, H.; Tisza, V.; Scatena, C.; Naccarato, A.G.; et al. Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine. Cancers 2022, 14, 4359. Citation Format: Thomas W. Campbell, Christian R. Hoerner, Elizabeth Alli, John T. Leppert, John C. Shon, Alice C. Fan. Development of a B-cell epitope classifier for early detection of renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1056.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

The DDD score outperforms the RENAL score in predicting high-grade renal cell carcinoma.

To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.

Texture analysis of CT- and MR-Images in the differential diagnosis of renal cell carcinoma: a review

INTRODUCTION: Renal cell carcinoma (RCC) is a heterogeneous group of diseases. The most common type of RCC is clear cell RCC. Tumor biopsy is the «gold» standard for verifying the diagnosis, however, it can be unsatisfactory due to the characteristic heterogeneity of the RCC structure. Non-invasive diagnostic methods — computed tomography and magnetic resonance imaging — in combination with the use of texture analysis can potentially provide a large amount of information about the structure of the kidney tumor and the presumed degree of its differentiation (grade).OBJECTIVE: Тo analyze publications devoted to texture analysis in RCC, the possibilities and prospects of using this method to increase the information content of CT and MR studies.MATERIALS AND METHODS: Our review presents data obtained from available sources PubMed, Scopus and Web of Science, published up to March 2022 inclusive, found using the keywords: renal cell carcinoma, CT, MRI, texture analysis, radiomics in Russian and English.RESULTS: The literature review describes the methods of texture analysis: selection of the region of interest, modality and contrast phase of the study, diagnostic aim. Based on the results of published scientific papers, the authors conclude that the use of texture analysis makes it possible to predict the grade of RCC with high sensitivity, specificity and accuracy, as well as to make a differential diagnosis of RCC with other kidney neoplasias, primarily lipid poor angiomyolipomas.CONCLUSION: The use of texture analysis based on published materials is extremely promising for non-invasive prediction of RCC grade and its differential diagnosis, however, the difference in methods and the lack of standardization of texture analysis requires additional research.

A Nuclei-Focused Strategy for Automated Histopathology Grading of Renal Cell Carcinoma.

The rising incidence of kidney cancer underscores the need for precise and reproducible diagnostic methods. In particular, renal cell carcinoma (RCC), the most prevalent type of kidney cancer, requires accurate nuclear grading for better prognostic prediction. Recent advances in deep learning have facilitated end-to-end diagnostic methods using contextual features in histopathological images. However, most existing methods focus only on image-level features or lack an effective process for aggregating nuclei prediction results, limiting their diagnostic accuracy. In this paper, we introduce a novel framework, Nuclei feature Assisted Patch-level RCC grading (NuAP-RCC), that leverages nuclei-level features for enhanced patch-level RCC grading. Our approach employs a nuclei-level RCC grading network to extract grade-aware features, which serve as node features in a graph. These node features are aggregated using graph neural networks to capture the morphological characteristics and distributions of the nuclei. The aggregated features are then combined with global image-level features extracted by convolutional neural networks, resulting in a final feature for accurate RCC grading. In addition, we present a new dataset for patch-level RCC grading. Experimental results demonstrate the superior accuracy and generalizability of NuAP-RCC across datasets from different medical institutions, achieving a 6.15% improvement in accuracy over the second-best model on the USM-RCC dataset.

Deep learning-assisted survival prognosis in renal cancer: A CT scan-based personalized approach

This paper presents a deep learning (DL) approach for predicting survival probabilities of renal cancer patients based solely on preoperative CT imaging. The proposed approach consists of two networks: a classifier- and a survival- network. The classifier attempts to extract features from 3D CT scans to predict the ISUP grade of Renal cell carcinoma (RCC) tumors, as defined by the International Society of Urological Pathology (ISUP). Our classifier is a 3D convolutional neural network to avoid losing crucial information on the interconnection of slides in 3D images. We employ multiple procedures, including image augmentation, preprocessing, and concatenation, to improve the performance of the classifier. Given the strong correlation between ISUP grading and renal cancer prognosis in the clinical context, we use the ISUP grading features extracted by the classifier as the input to the survival network. By leveraging this clinical association and the classifier network, we are able to model our survival analysis using a simple DL-based network. We adopt a discrete LogisticHazard-based loss to extract intrinsic survival characteristics of RCC tumors from CT images. This allows us to build a completely parametric survival model that varies with patients' tumor characteristics and predicts non-proportional survival probability curves for different patients. Our results demonstrated that the proposed method could predict the future course of renal cancer with reasonable accuracy from the CT scans. The proposed method obtained an average concordance index of 0.72, an integrated Brier score of 0.15, and an area under the curve value of 0.71 on the test cohorts.

Investigation of clear cell renal cell carcinoma grades using diffusion-relaxation correlation spectroscopic imaging with optimized spatial-spectrum analysis.

To differentiate high-grade from low-grade clear cell renal cell carcinoma (ccRCC) using diffusion-relaxation correlation spectroscopic imaging (DR-CSI) spectra in an equal separating analysis. Eighty patients with 86 pathologically confirmed ccRCCs who underwent DR-CSI were enrolled. Two radiologists delineated the region of interest. The spectrum was derived based on DR-CSI and was further segmented into multiple equal subregions from 2*2 to 9*9. The agreement between the 2 radiologists was assessed by the intraclass correlation coefficient (ICC). Logistic regression was used to establish the regression model for differentiation, and 5-fold cross-validation was used to evaluate its accuracy. McNemar's test was used to compare the diagnostic performance between equipartition models and the traditional parameters, including the apparent diffusion coefficient (ADC) and T2 value. The inter-reader agreement decreased as the divisions in the equipartition model increased (overall ICC ranged from 0.859 to 0.920). The accuracy increased from the 2*2 to 9*9 equipartition model (0.68 for 2*2, 0.69 for 3*3 and 4*4, 0.70 for 5*5, 0.71 for 6*6, 0.78 for 7*7, and 0.75 for 8*8 and 9*9). The equipartition models with divisions >7*7 were significantly better than ADC and T2 (vs ADC: P = .002-.008; vs T2: P = .001-.004). The equipartition method has the potential to analyse the DR-CSI spectrum and discriminate between low-grade and high-grade ccRCC. The evaluation of DR-CSI relies on prior knowledge, and how to assess the spectrum derived from DR-CSI without prior knowledge has not been well studied.

Prospective evaluation of core number of biopsy for renal tumor: are multiple cores preferable?

PurposeThis single-center, single-arm, prospective, open-label study was conducted to evaluate the optimal number of cores (single or multiple) in renal tumor biopsy.Materials and methodsForty-four biopsies of 44 tumors (mean diameter, 2.7 ± 1.0 cm; range, 1.6–5.0 cm) were included. Biopsy was performed under ultrasound or computed tomography fluoroscopy guidance using an 18-gauge cutting needle and the co-axial method. Two or more specimens were obtained, which were divided into first and subsequent specimens. “First specimen” and “all specimens” were histologically evaluated (i.e., appropriateness of specimen, histological diagnosis, subtype, and Fuhrman grade of renal cell carcinoma [RCC]) blindly and independently by two board-certified pathologists.ResultsMultiple specimens were successfully and safely obtained in all the biopsies. All tumors were histologically diagnosed; 40 malignancies included 39 RCCs and 1 solitary fibrous tumor, and 4 benign lesions included 2 angiomyolipomas, 1 oncocytoma, and 1 capillary hemangioma. In all RCCs, the subtype could be determined (32 clear cell RCCs, 4 chromophobe RCCs, and 3 papillary RCCs), and the Furman grade was determined in 38 RCCs. When only the first specimen was evaluated, 22.7% of the specimens were inappropriate for diagnosis, and 34 (77.3%) were histologically diagnosed. The diagnostic yield was significantly lower than that of all specimens (P = 0.0044). Univariate analysis revealed that smaller lesions were a significant predictor of diagnostic failure (P = 0.020).ConclusionBiopsy with multiple cores significantly improved diagnostic yield. Thus, operators should obtain multiple cores during renal tumor biopsy.