Sarcomatoid Differentiation Research Articles

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<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<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<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.

Genomic alteration of MTAP/CDKN2A predicts sarcomatoid differentiation and poor prognosis and modulates response to immune checkpoint blockade in renal cell carcinoma.

Sarcomatoid differentiation is a highly aggressive pathological characteristic of renal cell carcinoma (RCC) and is characterized by susceptibility to progression and extremely poor prognosis. In this study, we included all genomic alteration events that led to a loss of protein function of MTAP and CDKN2A, and enrolled 5,307 RCC patients with genomic sequencing data from Western and Chinese cohorts. Notably, MTAP/CDKN2A MUT occurred in the Chinese population ~2 times more frequently than in the Western cohort and showed significant co-mutation trends. We found significantly higher proportions of sarcomatoid-positive patients with MTAP MUT or CDKN2A MUT compared with MTAP/CDKN2A wild-type (WT) patients (P < 0.001). Of the 574 RCC samples from the FUSCC cohort and 3,563 RCC samples from 17 independent cohorts, the MTAP/CDKN2A MUT significantly predicted extremely poor outcomes (P < 0.0001). The Western cohort suggested a concordant relationship between MTAP/CDKN2A MUT and sarcomatoid differentiation in RCC. Moreover, although MTAP/CDKN2A MUT RCC may be insensitive to targeted therapy, the high degree of tumor heterogeneity and higher PD-L1 and CXCL13 expression characterizations reflected that MTAP/CDKN2A-deficient features could benefit from immunotherapy for patients with RCC. This study utilized RCC samples from large-scale, global, multicenter sequencing cohorts and first proved that MTAP/CDKN2A deficiency significantly correlates with sarcomatoid differentiation in RCC and predicts aggressive progression, poor prognosis, and primary resistance to targeted therapy and potential favorable responses to immune checkpoint blockade. Unlike conventional targeted therapies, emerging drugs such as immunotherapies or synthetic lethal PRMT5 inhibitors may become novel therapeutic options for patients with MTAP/CDKN2A MUT RCC.

Papillary Type Renal Cell Carcinoma with Sarcomatoid Differentiation

Renal cell carcinoma is the most common renal tumor in adult population. Sarcomatoid differentiation of renal cell carcinoma is quite aggressive in nature and has poor prognosis. In this study, a case of 69-year-old female patient who initially presented with hematuria was discussed.

The prognostic value of preoperative neutrophil-to-lymphocyte ratio in patients with non-metastatic renal cell carcinoma

The aim of this study was to investigate the prognostic significance of the preoperative neutrophil-to-lymphocyte ratio in non-metastatic renal cell carcinoma. We retrospectively analyzed the records of patients with non-metastatic renal cell carcinoma who were operated between 2004 and 2020 at our institution. The Kaplan-Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox's proportional hazards regression models were utilized to analyze the association between neutrophil-to-lymphocyte ratio and oncological outcomes. We included 202 patients. Patients with higher neutrophil-to-lymphocyte ratio had larger tumors (P=0.03), higher ASA score (P=0.014), clinical symptoms (P=0.04), sarcomatoid differentiation (P=0.03) and tumor necrosis (P=0.02). The rates of recurrence-free survival and metastasis-free survival were significantly lower in patients with a high neutrophil-to-lymphocyte ratio than in those with a low ratio (P=0.017; P=0.036 respectively). Multivariate analysis identified the neutrophil-lymphocyte ratio as an independent predictor of recurrence-free and metastasis-free survival (P=0.021; P=0.001 respectively). A higher neutrophil-to-lymphocyte ratio has been associated with a symptomatic renal cancer with a significant prognostic factor for both recurrence-free and metastasis-free survival. 3.

Clinicopathologic and Immunohistochemical Characterization of Sarcomatoid Chromophobe Renal Cell Carcinoma: An Analysis of 22 Cases.

Sarcomatoid differentiation in chromophobe renal cell carcinoma (ChRCC) is a rare finding and a significant predictor of worse outcomes. When the sarcomatoid component overgrows the conventional component or is the only component on a biopsy, the differential diagnoses encompass a variety of entities. Therefore, we reviewed 22 sarcomatoid ChRCCs and characterized the immunophenotype. Given that renal carcinomas with sarcomatoid features may benefit from immune checkpoint inhibitor-based therapy we also assessed the programmed death-ligand 1 (PD-L1) (28-8) expression. DOG1, CD117, cytokeratin 7, and PAX8 were negative in 100%, 88%, 63%, and 44% of the sarcomatoid components, respectively. GATA3 was expressed in 31% of the conventional components and in 50% of the sarcomatoid components. One conventional and 3 sarcomatoid components expressed PD-L1. Sarcomatoid ChRCCs have a high propensity for metastases and cancer progression. Distant metastatic disease was seen in 73% of the cases and median survival in this cohort was <1 year. The sarcomatoid portion had increased expression of PD-L1 and frequent loss of expression of multiple immunohistochemical markers associated with ChRCC. Half of the sarcomatoid ChRCC exhibited GATA3 expression, 3 of which did not express PAX8.

Papillary renal cell carcinoma: a single institutional study of 199 cases addressing classification, clinicopathologic and molecular features, and treatment outcome

AbstractThe morphologic spectrum of type 1 papillary renal cell carcinoma (PRCC) is not well-defined, since a significant proportion of cases have mixed type 1 and 2 histology. We analyzed 199 cases of PRCC with any (even if focal) type 1 features, with a median follow-up of 12 years, to identify clinicopathological features associated with outcome. Ninety-five tumors (48%) of the cohort contained some type 2 component (median amount: 25%; IQR: 10%, 70%). As a group they showed high rates of progression-free (PFS) and cancer-specific survival (CSS). Tumor size, mitotic rate, lymphovascular invasion, sarcomatoid differentiation, sheet-like architecture, and lack of tumor circumscription were significantly associated with CSS (p ≤ 0.015) on univariate analysis. While predominant WHO/ISUP nucleolar grade was associated with PFS (p = 0.013) and CSS (p = 0.030), the presence of non-predominant (<50%) nucleolar grade did not show association with outcome (p = 0.7). PFS and CSS showed no significant association with the presence or the amount of type 2 morphology. We compared the molecular alterations in paired type 1 and type 2 areas in a subset of 22 cases with mixed type 1 and 2 features and identified 12 recurrently mutated genes including TERT, ARID1A, KDM6A, KMT2D, NFE2L2, MET, APC, and TP53. Among 78 detected somatic mutations, 61 (78%) were shared between the paired type 1 and type 2 areas. Copy number alterations, including chromosome 7 and 17 gains, were similar between type 1 and 2 areas. These findings support that type 2 features in a PRCC with mixed histology represent either morphologic variance or clonal evolution. Our study underscores the notion that PRCC with any classic type 1 regions is best considered as type 1 PRCC and assigned the appropriate WHO/ISUP nucleolar grade. It provides additional evidence that type 2 PRCC as a separate category should be re-assessed and likely needs to be abandoned.

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes.

Background and ObjectiveThe histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial. They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy. There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH.MethodsA PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC.Key Content and FindingsNeoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present.ConclusionsBased on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

Histologic diversity in chromophobe renal cell carcinoma does not impact survival outcome: A comparative international multi-institutional study

Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome.This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched.Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation.Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets.

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.

MP50-08 THE PROGNOSTIC SIGNIFICANCE OF LYMPH NODE DISSECTION IN PATIENTS WITH NON-METASTATIC RENAL CELL CARCINOMA WHO UNDERWENT CURATIVE NEPHRECTOMY: A RETROSPECTIVE, LONG-TERM FOLLOW-UP, MULTICENTER STUDY CARCINOMA (NMRCC) WHO UNDERWENT CURATIVE NEPHRECTOMY

You have accessJournal of UrologyCME1 May 2022MP50-08 THE PROGNOSTIC SIGNIFICANCE OF LYMPH NODE DISSECTION IN PATIENTS WITH NON-METASTATIC RENAL CELL CARCINOMA WHO UNDERWENT CURATIVE NEPHRECTOMY: A RETROSPECTIVE, LONG-TERM FOLLOW-UP, MULTICENTER STUDY CARCINOMA (NMRCC) WHO UNDERWENT CURATIVE NEPHRECTOMY Sung Han Kim, Jinsoo Chung, Hyung Ho Lee, Boram Park, Seok Soo Byun, Chang Wook Chung, Sung Hoo Hong, Eu Chang Hwang, and Cheol Kwack Sung Han KimSung Han Kim More articles by this author , Jinsoo ChungJinsoo Chung More articles by this author , Hyung Ho LeeHyung Ho Lee More articles by this author , Boram ParkBoram Park More articles by this author , Seok Soo ByunSeok Soo Byun More articles by this author , Chang Wook ChungChang Wook Chung More articles by this author , Sung Hoo HongSung Hoo Hong More articles by this author , Eu Chang HwangEu Chang Hwang More articles by this author , and Cheol KwackCheol Kwack More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002625.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To evaluate the prognostic impact of lymph node dissection (LND) on recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent curative nephrectomy. METHODS: A retrospective, five-center study of 1328 nmRCC patients was performed between 2000 and 2012, and the patients were followed up until the end of 2018. Survival measures were compared according to the performance of the LND (LND vs. no LND groups) and the presence of node positivity (N+ and N- groups), while Kaplan-Meier analysis with the log-rank test and Cox regression analysis was used to determine the prognostic risk factors for each survival measure. RESULTS: During the median 55.8-month follow-up, 405 (30.5%) recurrences, 207 (15.6%) deaths, including 189 (14.0%) cancer-specific deaths, were recorded. The risk factor analyses showed that predictive factors for CSS and OS were similar, such as pathologic and clinical T stage, nuclear grade, European Cooperative Oncology Group Score, and albumin, neutrophil, and lymphocyte levels. Meanwhile, sarcomatoid differentiation was found as an additional predictive factor for CSS, while nephrectomy type and diabetes were found as additional predictive factors for OS (p<0.05). For RFS, additional factors such as sarcomatoid differentiation, necrosis, and lymphovascular invasion were present and significant (p<0.05). After adjusting for significant clinicopathological factors affecting survival outcomes considering the hazard ratios of each group in the multivariate analysis, the LND N+ group showed significantly worse prognoses for all survival types (p<0.05). Meanwhile, in the no-LND and LND without positive nodal groups, there was no significant difference between any survival type. (p>0.05). CONCLUSIONS: This study showed that nodal positivity significantly affected RFS, whereas LND significantly affected OS and CSS, in patients with nmRCC who underwent curative nephrectomy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e867 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sung Han Kim More articles by this author Jinsoo Chung More articles by this author Hyung Ho Lee More articles by this author Boram Park More articles by this author Seok Soo Byun More articles by this author Chang Wook Chung More articles by this author Sung Hoo Hong More articles by this author Eu Chang Hwang More articles by this author Cheol Kwack More articles by this author Expand All Advertisement PDF DownloadLoading ...

Magnetic resonance imaging (MRI) helps differentiate renal cell carcinoma with sarcomatoid differentiation from renal cell carcinoma without sarcomatoid differentiation.

The aim of the present study is to identify predictive imaging findings and construct a diagnostic model for differentiating renal cell carcinoma (RCC) with and without sarcomatoid dedifferentiation (sRCC and non-sRCC). This study is a single-center retrospective study. All patients had magnetic resonance imaging (MRI) with gradient-echo T1-weighted images, single-shot T2-weighted images (T2WI), and enhanced nephrographic phase images. Forty pathologically confirmed sRCCs and 80 non-sRCCs were included in this study. Control cases were selected by matching the tumor diameter and the year of MRI. Two radiologists independently evaluated the following findings: growth pattern, presence of low-intensity area on T2WI in the tumor (T2LIA), presence of non-enhancing area, local tumor stage, and presence of regional lymphadenopathy. Two radiologists measured the diameter of the tumor, T2LIA, and the non-enhancing area. Multivariable logistic regression analysis was used to identify independent predictive factors for differentiating sRCC from non-sRCC. Selected variables were entered in the logistic regression model, and the area under the curve (AUC) was calculated for each reader with 95% confidence intervals (CIs). Larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 were associated with sRCC, and selected for the subsequent construction of a logistic regression model. With this model, the AUCs were 0.76 (95% CI, 0.66-0.85) and 0.70 (95% CI, 0.59-0.81) for prediction of sRCC. In conclusion, larger T2LIA-to-tumor diameter ratio, regional lymphadenopathy, and local tumor stage 4 are predictive findings of sRCC. As a result, the model constructed using these findings demonstrated a moderate degree of diagnostic accuracy.

Neutrophil-to-Lymphocyte Ratio Predicts Cancer Outcome in Locally Advanced Clear Renal Cell Carcinoma

To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy. We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan-Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS. Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P=.045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P=.03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4. For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.

Preoperative Platelet Distribution Width Represents a Novel Prognostic Biomarker in Patients With Nonmetastatic Renal Cell Carcinoma: A Retrospective Clinical Analysis

PurposeThe study aimed to explore the prognostic value of platelet distribution width (PDW) in patients with nonmetastatic renal cell carcinoma (RCC).MethodsWe retrospective analyzed 706 patents with nonmetastatic RCC from January 2015 to December 2017. Clinicopathologic data and platelet indices were collected and analyzed by univariable and multivariable cox proportional hazard model. Progression-free survival (PFS) was analyzed using the Kaplan–Meier curve. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were performed to evaluate the improvement of predictive accuracy.ResultsPatients were divided into low PDW (N = 241, PDW ≤11.7%), intermediate PDW (N = 232, 11.7%< PDW ≤15.6%), and high PDW (N = 233, PDW >15.6%) groups according to the tertiles. Patients with low PDW were associated with more symptoms at presentation, larger tumor size, higher AJCC tumor stage, and more sarcomatoid differentiation. Besides, patients with low PDW had significantly shorter PFS compared to intermediate PDW and high PDW groups. On the multivariable model, AJCC tumor stage, nuclear grade, and PDW (either continuous or categorical variables) were independent factors correlated with PFS. The NRI and IDI showed adding PDW to SSIGN score improves its predictive accuracy related to 2-, 3-, and 4-year PFS.ConclusionsLow PDW was related to advanced clinicopathologic features and worse prognosis in patients with nonmetastatic RCC. Thus, PDW could serve as a novel biomarker for risk stratification in these patients when used pre-or postoperatively.

Early Recurrence of Cromophobic Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Differentiation: About a Case

Chromophobic renal cell carcinoma with sarcomatoid differentiation is a rare tumor characterized by a biphasic tumor with both classic epithelial components and sarcomatoid components with poor prognostic factors, usually in association with the rhabdoid contingent which has the potential to behave aggressively and metastasize. We report a particular case of recurrence of this entity in a male patient in which the diagnosis was suspicious preoperatively for the tumor evolution time and the size of the mass and the imaging data performed. The patient underwent extensive left total nephrectomy and lymph node dissection. The postoperative follow up was marked by early appearance of recurrence within 6 weeks after surgery.

A Nomogram Predicting the Progression-Free Survival of Nonmetastatic Renal Cell Carcinoma Patients With Venous Thrombus After Surgery.

ObjectivesTo demonstrate the progression-free survival (PFS) of nonmetastatic renal cell carcinoma (RCC) patients with venous thrombus after radical nephrectomy and venous thrombectomy (RN-VT) and to develop and validate a nomogram to predict the PFS of patients after RN-VT.Materials and MethodsWe reported our prospective follow-up data of RCC patients with venous thrombus from January 2014 to September 2020 (n = 199). We used the Kaplan–Meier method to assess the PFS. The Cox proportional hazards regression model was used to determine the predictors. Nomograms predicting the PFS was established, and external validation was performed. Calibration curves and decision curves were generated to assess the predictive efficacy and clinical benefit.ResultsAfter a median follow-up of 32 months, 79 patients (39.7%) had disease progression and the median PFS was 41.0 months (95% CI 34.8–53.2 months). The 1-year, 3-year, and 5-year PFS rates were 78.4%, 45.4%, and 30.0%, respectively. Multivariate analysis showed that Fuhrman grade [grade 4: hazard ratio (HR) 1.92, 95% CI 1.10–3.34, P = 0.02], pathological type (papillary RCC: HR 3.02, 95% CI 1.79–5.10, P < 0.001), perinephric fat invasion (HR 1.54, 95% CI 1.12–2.10, P = 0.007), sarcomatoid differentiation (HR 2.97, 95% CI 1.24–7.13, P = 0.02) were associated with a worse PFS, and adjuvant therapy (HR 0.32, 95% CI 0.18–0.59, P < 0.001) could lead to a better PFS. A nomogram based on the predictors was externally validated to have good discrimination and calibration, and it could improve PFS prediction to obtain a clinical benefit.ConclusionsWe constructed and validated a nomogram to predict the 1-year, 3-year, and 5-year PFS of M0 RCC patients with venous thrombus after surgery. The model can help identify patients who can benefit the most from surgery and develop the criteria for clinical trial enrollment.

Prognostic impact of prognostic nutritional index on renal cell carcinoma: A meta-analysis of 7,629 patients.

BackgroundPrognostic nutritional index (PNI) is a parameter which reflects nutritional and inflammatory status. The prognostic value of PNI in renal cell carcinoma (RCC) remains in debate. The aim of this study is to evaluate the prognostic value and clinicopathological features of PNI in RCC.MethodsA literature search was performed in the databases of PubMed, Embase, Web of Science, and Cochrane Library. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were extracted for meta-analysis. The association between PNI and overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS), recurrence-free survival (RFS), and clinicopathological factors were evaluated.ResultsEleven studies involving 7,629 patients were included for meta-analysis. A decreased PNI was shown to be a significant predictor of worse OS (HR = 2.00, 95%CI = 1.64–2.42, p<0.001), CSS (HR = 2.54, 95%CI = 1.61–4.00, p<0.001), and DFS/PFS/RFS (HR = 2.12, 95%CI = 1.82–2.46, p<0.001) in RCC. Furthermore, a low PNI was correlated with Fuhrman grade III-IV (OR = 1.96, 95%CI = 1.27–3.02, p = 0.002), T stage T3-T4 (OR = 2.21, 95%CI = 1.27–3.87, p = 0.005), presence of sarcomatoid differentiation (OR = 5.00, 95%CI = 2.52–9.92, p<0.001), and presence of tumor necrosis (OR = 3.63, 95%CI = 2.54–5.19, p<0.001).ConclusionPNI is an independent prognostic indicator of survival and associated with Fuhrman grade, T stage, sarcomatoid differentiation, and tumor necrosis in patients with RCC.

Oncologic Outcomes of Renal Cell Carcinoma Patients Undergoing Radical Nephrectomy and Venous Thrombectomy: Prospective Follow-Up from a Single Center.

Purpose To evaluate the long-term oncologic outcomes of renal cell carcinoma (RCC) patients with venous thrombus after radical nephrectomy and venous thrombectomy (RN-VT) and to determine the prognostic factors. Methods and Materials We reported our follow-up data of RCC patients with venous thrombus from January 2014 to September 2020. We used the Kaplan-Meier method to assess the overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). The Cox proportional hazards regression model and competing risk model were used. Results After a median follow-up of 31 mon, eight-five patients (31.5%) died, and cancer-specific deaths occurred in 60 patients (22.2%). The 1 yr and 3 yr CSS were 89.3% and 72.7%, respectively. The median OS was 56.0 mon (95% CI 47.6-64.3 mon), and the 1 yr, 3 yr, and 5 yr OS were 87.0%, 62.1%, and 44.8%, respectively. For M1 patients, the median OS was 27.0 mon (95% CI 22.0-42.0 mon), and the 1 yr, 3 yr, and 5 yr OS were 78.0%, 41.5%, and 23.3%, respectively. For M0 patients, the median RFS was 38.0 mon (95% CI 32.5-43.5 mon), and the 1 yr and 3 yr RFS were 81.2% and 52.3%, respectively. Multivariate analyses showed that papillary RCC (HR 2.95, 95% CI 1.80-4.82, P < 0.001) or other RCC (HR 3.88, 95% CI 2.03-7.41, P < 0.001), perinephric fat invasion (HR 1.53, 95% CI 1.03-2.26, P = 0.04), sarcomatoid differentiation (HR 2.85, 95% CI 1.64-4.95, P < 0.001), Fuhrman grade 3 (HR 2.10, 95% CI 1.28-3.44, P = 0.003) or 4 (HR 3.55, 95% CI 2.09-6.03, P < 0.001), and distant metastasis (HR 1.76, 95% CI 1.18-2.63, P = 0.006) were associated with a worse CSS. Adjuvant therapy (HR 0.63, 95% CI 0.43-0.92, P = 0.02) was associated with a better CSS. Conclusions RCC patients can have an acceptable long-term survival after RN-VT. Prognostic factors influencing CSS included nonclear cell RCC histology, higher Fuhrman grade, sarcomatoid differentiation, perinephric fat invasion, distant metastasis, and adjuvant therapy.

Survival outcomes of metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation (SD): A single-institutional experience and literature meta-analysis.

332 Background: Patients (pts) with mRCC with SD have unfavorable outcomes and poor prognosis due to aggressive tumor behavior. Chemotherapy and targeted treatment are often of little benefit. However, recent studies have shown a survival benefit of immunotherapy (IO). Here, we report survival outcomes of pts with mRCC with SD treated with first line IO or chemotherapy or targeted treatment. In addition we performed a meta-analysis of recent practice changing phase III, IO trials in mRCC. Methods: This retrospective survival analysis was performed in pts with mRCC with SD treated with IO or non-IO treatment at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method (log-rank). PFS and OS hazard ratios (HR) were calculated using cox proportional hazards model. We identified the major, practice changing clinical trials that reported survival outcomes of mRCC with SD treated with IO and performed a random-effects meta-analysis of HR for PFS and OS. We compared these pooled results to our single institution experience. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. In total, 44 (9.3%) pts had mRCC with SD who were treated with IO or non-IO. Of these, 29 (65.9%) pts had pure SD and 15 (34.1%) pts had mixed rhabdoid and SD features. Median age was 59.6 years (36-78) and 33 (75%) were male. Overall, as per the IMDC score, 3(6.8%), 21(47.7%) and 20(45.5%) pts were categorized as good, intermediate, and poor risk, respectively. Eight (18.2%) pts were treated with IO as first line of treatment, and 36 (81.8%) pts received non-IO. With a median follow up of 64.8 months (range, 45.7-83.8 months), the median OS for the whole mRCC with SD cohort was 15.6 months (95% CI: 8.6-22.5). The median OS in all pts treated with IO vs non-IO was not reached vs 10.3 months (95%CI: 1.49-19.1 months; p = 0.005), respectively. The HR for OS was 0.1 (95%CI: 0.01-0.78; p = 0.023) favoring IO receipt. The median PFS in all pts treated with IO vs non-IO was 24 months (95%CI: non-estimable) vs 5.4 months (95%CI: 2.9-7.8 months; p = 0.021), respectively. The HR for PFS was 0.3 (95%CI: 0.11-0.89; p = 0.03) favoring IO receipt. We identified through meta-analysis five phase III clinical trials reporting PFS and OS in pts with mRCC with SD who received IO. The overall HR for OS and PFS for the total cohort were 0.55 (95%CI: 0.41-0.74), and 0.53 (95%CI: 0.42-0.67), respectively. Conclusions: Our meta-analysis has confirmed the benefit of IO agents in mRCC with SD. While the numbers included in this retrospective review were small, they have provided real world corroboration of the trial findings. Pts with mRCC and SD benefit from IO treatment, which should be considered the standard of care for these patients.

CD70 is a promising CAR-T cell target in patients with advanced renal cell carcinoma.

384 Background: Renal cell carcinoma (RCC) comprises a heterogeneous group of tumors of different histological subtypes. Each subtype is characterized by distinct immunohistochemical and molecular features and different biology. Currently, patients with advanced RCC have poor disease outcomes despite recent breakthroughs in immunotherapy. Chimeric antigen receptor (CAR)-T cell therapy has produced remarkably effective and durable clinical responses in hematological malignancies. However, there have been very limited success of CAR-T cell therapy in solid tumors. CD70 and its signaling partner CD27 are cell surface molecules that have emerged as novel targets for immune modulation approach. CD70 is also a promising target for CAR-T cell therapy, as it is overexpressed on multiple types of solid tumors including RCC and not expressed in most normal tissue. Studies have shown clear cell RCC (CCRCC) commonly expresses CD70. To date, no studies has evaluated CD70 expression in metastatic RCC in comparison with primary RCC. Methods: Four Tissue Microarrays (TMAs) were constructed using 395 tumors from 374 patients with RCC, 4 to 8 cores per tumor. There were 359 primary tumors, 36 metastatic tumors, and 344 matched normal. The primary RCC included 309 CCRCC including 11 with sarcomatoid differentiation, 38 papillary RCC (pRCC) including 1 with sarcomatoid differentiation, 8 chromophobe RCC (ChRCC), and 4 collecting duct RCC (CDC). The metastatic RCC were composed of 31 CCRCC including 3 with sarcomatoid differentiation and 5 PRCC. CD70 expression was evaluated using immunohistochemistry (IHC) and Definiens image analysis. CD70 expression was measured using the percentage of CD70-positive tumor cells. A CD70-positive tumor was defined as CD70 immunopercentage ≥ cutoff value in at least one core. Results: CD70 staining was detected in tumor cells in primary and metastatic RCC, with minimal staining in normal renal parenchyma. When the positive cutoff was defined as ≥1% of tumor cells demonstrating CD70 staining, the positive rate in CCRCC, pRCC, ChRCC, CDC, and SarRCC was 98%, 32%, 0%, 11%, and 46%, respectively. When the positive cutoff was defined as ≥ 25% of tumor cells stained positive for CD70, the positive rate in CCRCC, pRCC, ChRCC, CDC, and SarRCC was 41%, 10%, 0%, 0%, and 23%, respectively. Finally, when the positive cutoff was defined as ≥50%, the positive rate in CCRCC, pRCC, ChRCC, CDC, and SarRCC was 22%, 2%, 0%, 0%, and 8%, respectively. Metastatic RCC showed a higher % of tumor cells expressing CD70 compared to primary RCC for patients with CCRCC (mean 15% vs 9%) or SarRCC (12% vs 9%). Conclusions: Clear cell and sarcomatoid RCC are the RCC subtypes that demonstrate the highest CD70 expression. CD70 expression is further increased in metastatic lesions compared to the primary tumors. Anti-CD70 CAR-T cell therapy may benefit a significant fraction of patients with advanced CCRCC and sarcomatoid RCC.

Pathologic outcomes at cytoreductive nephrectomy (CN) following immunotherapy (IO) for patients with advanced renal cell carcinoma (RCC).

334 Background: IO, either as combination therapy in the frontline or monotherapy in the second line, has improved outcomes for patients with advanced RCC. With the movement away from upfront CN, limited data are available on the outcomes of patients who receive IO with delayed CN. In this study, we characterized the pathologic and survival outcomes for patients who received IO followed by CN. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO combination or monotherapy followed by CN. An IRB-approved and HIPAA-compliant registry was used to collect data from the electronic medical record. Our primary endpoint was the degree of pathologic downstaging comparing baseline clinical T stage to pathologic T stage following IO. Secondary endpoints included investigator assessed response using RECIST principals, progression-free survival (PFS), and overall survival (OS). Results: We identified53 patients with advanced RCC across 9 institutions who were eligible for the study. The median age was 63 years, 72% were white, and 60% were male. 81% of patients had clear cell histology, 11% had sarcomatoid differentiation, and 75% presented with de novo metastatic disease. Baseline IMDC risk is as follows: 4% favorable, 55% intermediate, and 26% poor risk with 15% unknown. 23% had bone metastases and 23% had liver metastases at baseline. Lines of therapy prior to CN was 1 line in 74% of patients, 2 lines in 25%, and 3 lines in 2%. For the line of IO therapy immediately preceding CN, 49% received nivolumab+ipilimumab, 30% received IO monotherapy, and 21% received combination IO/VEGF therapy. The median duration of therapy prior to surgery was 11.3 months (range 0.38-47.8). 28% of patients discontinued treatment after CN for observation. Best overall response prior to CN was stable disease in 25% of patients, partial response in 60%, and progressive disease in 4% with 11% unknown. Following receipt of IO-based treatment, 38% of patients exhibited downstaging from the baseline clinical T stage to the CN pathological T stage (Table). 11% of patients had no residual disease at CN. For pathologic outcomes, 85% of patients had negative margins, 75% had necrosis present, and the median tumor size at CN was 6.5 cm. The median PFS was 11.3 months and median OS was 25.7 months for the overall cohort. Conclusions: IO-based strategies demonstrate efficacy in the renal primary in patients with advanced RCC. T stage downstaging was demonstrated in 38% of patients with 11% having a complete pathologic response in the renal primary following IO administration. Biomarker studies on baseline and CN tissue will further elucidate molecular predictors of response and resistance to IO therapy.[Table: see text]