International Metastatic Renal Cell Carcinoma Database Consortium Model Research Articles

A novel prognostic model for oligometastatic renal cell carcinoma: COMPARZ study post-hoc analysis.

e16521 Background: International metastatic renal cell carcinoma database consortium (IMDC) is the most commonly used prognostic model for metastatic renal cell carcinoma (mRCC), however, its clinical application has been limited due to the cumbersome design and vague recommendation of treatment decisions for patients in the IMDC intermediate risk group. Previous studies indicated the favorable prognosis of oligometastatic RCC, but the definition of oligometastasis has not been clarified. This study aims to construct a new prognostic model of oligometastatic RCC based on the COMPARZ study cohort. Methods: Patients from the COMPARZ study (which was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in advanced RCC or mRCC patients). Patients (N=1038) were divided into two cohorts for models construction respectively, Cohort A (n=293) with primary kidney tumor; Cohort B (n=745) without primary kidney tumor. Multivariate Cox regression analysis was performed to identify the independent prognostic risk factors for each model with overall survival (OS) as primary endpoint. Uno’s C-statistics was utilized to compare the novel risk model with IMDC risk. These models were then used to examine and stratify the patients in IMDC intermediate risk group. Results: In Cohort A, four risk factors were identified independent predictors for short survival. Patients were segregated into the oligo group and the non-oligo group. The concordance index (C-index) for Model A and IMDC risk model was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.61-0.69), respectively (p=0.389). In Cohort B, three risk factors were identified as independent predictors of short survival. Patients were also divided into the oligo group and the non-oligo group. The C-index between Model B and IMDC risk model was 0.62 (95%CI: 0.59-0.64) and 0.61 (95%CI: 0.58-0.64), respectively (p=0.650). For Model A, mOS for non-oligo group was 13.4 months vs NR in oligo group (3y OS: 25.3 vs 51.8%), while for model B, mOS was 18.5 vs NR respectively (3y OS: 24.3 vs 57.5%). With the novel prognostic models, patients in the IMDC intermediate risk group could be further stratified into oligo group (mOS: NR; 3y OS: 55.6%) that had a better outcome than patients in non-oligo group (mOS: 19.2 month; 3y OS: 24.9%; p<0.001). Conclusions: Compared with the current IMDC model, the novel prognostic models of oligometastatic mRCC could well distinguish patients into favorable and poor prognostic groups with fewer risk factors and comparable predictive power. Meanwhile, the novel models can better stratify the IMDC intermediate risk group into oligo and non-oligo groups with significantly different OS outcomes, and is more conductive to the comprehensive treatment of patients with mRCC.

External Validation of a Novel Risk Model in Patients With Favorable Risk Renal Cell Carcinoma Defined by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC): Results From the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.

A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the International mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt etal., 3 parameters (ie, time from diagnosis to systemic therapy <3 vs. ≥3 years, Karnofsky Performance Status [KPS] 80 vs. >80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P=.025) and TTF (25.5 months vs. 15.5 months, P=.010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P=.573). This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021.

Prognostic significance of 18F-FDG PET/CT indices in metastatic renal cell cancer and evaluation of revised IMDC risk model by including 18F-FDG PET-CT parameters.

Prognostic markers in metastatic renal cell cancer (mRCC) are still insufficient. Any prognostic model objectively determines disease burden. To investigate the relationship between 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and outcomes in mRCC, and to define a revised International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model for the intermediate-risk group. A retrospective study of mRCC was conducted. To investigate the prognostic significance of 18F-FDG PET/CT parameters, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were determined in pre-treatment images. Cutoff values were defined by ROC curve analyses and their association with outcomes was analyzed. Additionally, a TLG-adjusted IMDC model was created by stratifying intermediate-risk group patients according to TLG levels. The study included 52 patients. The disease control rate (DCR) was 61.5% and median overall survival (OS) was 18 months (95% confidence interval=9.2-25.8). In the univariate analyses, IMDC score, MTV, and TLG were prognostic factors for Disease Control Rate (DCR), and Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS), IMDC score, lactate dehydrogenase (LDH), treatment option, MTV, and TLG were prognostic factors for OS (P < 0.05 each). In the multivariate analyses, MTV was an independent prognostic factor for DCR, and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. According to the revised-IMDC model, the intermediate-favorable group showed longer OS than the intermediate-unfavorable group. Pretreatment MTV was independent prognostic factor for DCR and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. Revised-IMDC model could identify patients with a worse prognosis among the IMDC intermediate-risk group.

Impact of modified Glasgow prognostic score on predicting prognosis and modification of risk model for patients with metastatic renal cell carcinoma treated with first line tyrosine kinase inhibitor.

Intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria is thought to consist of patients with different prognoses. This study investigated the impact of a pretreated modified Glasgow prognostic score (mGPS), which is defined on the basis of the pretreated serum albumin and C-reactive protein level, on predicting the prognosis of patients with metastatic renal cell carcinoma (mRCC) and its usefulness for the re-stratification of patients into a more improved risk model. One hundred ninety-six mRCC patients treated with first-line tyrosine kinase inhibitor (TKI) were retrospectively investigated. All patients were classified into either a high-mGPS or a low-mGPS group on the basis of mGPS score upon starting systemic therapy, the overall survival (OS) and cancer specific survival (CSS) rates in each group were compared. We use decision curve analysis and calculate C-index based on OS and CSS to compare IMDC+mGPS model and IMDC model. The categories of favorable, intermediate, and poor risk groups in the IMDC model were assessed in 32, 113, and 51 cases, respectively. The low- and high-mGPS groups consisted of 149 and 47 cases. The median OS in the high- and low-mGPS groups were 38.4 months and 5.6 months, and their median CSSs were 41.0 months and 5.6 months, respectively (P < 0.0001). Multivariate analysis showed that a high mGPS, multiple metastatic organs, and hypercalcemia were independent predictive factors for a worse OS (P = 0.0260). Next, we divided the intermediate risk group into two subgroups using the mGPS score. The OS and CSS for the high-mGPS subgroup were significantly worse than those for the low-mGPS one (P = 0.0024, median OS: 21.0 months and 33.7 months, P = 0.0007, median CSS: 21.0 months and 39.8 months), and there was no significant difference in OS between the high-mGPS subgroup in the intermediate risk group and poor risk group (P = 0.2250). The value of C-index based on OS at IMDC and IMDC+mGPS model were 0.6771 and 0.6967, and those based on CSS were 0.6850 and 0.7080, respectively. In decision curve analysis to evaluate the clinical net benefit using the IMDC+mGPS model compared to the IMDC model, there was no significant difference between the two groups. mGPS is useful for establishing a more improved prognostic model that is able to stratify mRCC patients treated with first-line TKI.

Perirenal Fat Thickness Significantly Associated with Prognosis of Metastatic Renal Cell Cancer Patients Receiving Anti-VEGF Therapy.

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value.

Clinicopathological characteristics and prognosis of metastatic collecting duct carcinoma

To investigate the clinicopathological characteristics, response to different treatment regimens, and prognostic factors of metastatic collecting duct carcinoma (CDC). Information of patients with metastatic CDC was retrieved from a database including clinical and survival data. Survival outcomes were analyzed with the Kaplan-Meier method, and prognostic factors were identified with the Cox proportional hazard model. Fifty patients with metastatic CDC were included in this study. Most patients had an advanced T stage (58% T3-4) and high WHO/ISUP grade (86% G3-4). Twenty-nine patients (58%) developed metastases from an early stage, 42% had distant metastases at diagnosis, and 28% received cytoreductive nephrectomy. In the first-line setting, the objective response rate was 27.0%, and the median progression-free survival was 6.4 months (95%CI 4.9-7.9) for 37 patients who received chemotherapy combined with sorafenib. One PR was seen in 4 patients who received anti-PD-1 antibody plus axitinib. The median overall survival for the whole population was 12.6 months (95%CI 7.8-17.4). In univariate analyses, advanced T stage, East Cooperative Oncology Group Performance Score ≥1, anemia, elevated lactate dehydrogenase, and no response to first-line treatment was associated with poor prognosis (P < 0.05). In multivariate analyses, advanced T stage and anemia were independently associated with a poorer prognosis. The Memorial Sloan-Kettering Cancer Center (MSKCC) model (P = 0.002) predicted the prognosis of metastatic CDC patients more accurately than the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) model (P = 0.063). T Stage and anemia were independent prognostic factors for metastatic CDC. MSKCC was more accurate than the IMDC model to predict the outcome. Chemotherapy plus sorafenib demonstrated substantial efficacy in the first-line setting. Anti-PD-1 plus axitinib showed a preliminary antitumor effect and is worthy of further exploration.

Prognostic factors for patients with advanced renal cell carcinoma (aRCC) in the era of first-line (1L) treatment with immune checkpoint inhibitors (ICIs).

4544 Background: The most commonly used prognostic models in aRCC, the Memorial Sloan-Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, were developed when cytokines and VEGF targeted monotherapies were standard of care, respectively. aRCC 1L treatment now includes combination therapy with 2 ICIs or ICI+VEGF receptor inhibitor. Re-evaluation of the MSKCC and IMDC prognostic models in the era of ICI therapy and identification of additional prognostic factors are overdue. Methods: Data from 1052 patients with aRCC treated on the CheckMate-214 (CM214) clinical trial with 1L nivolumab/ipilimumab (NIVO/IPI) or sunitinib (SUN) were analyzed retrospectively at median follow-up 5 yrs. For each treatment group, multivariable Cox model hazard ratios (HR) were compared to the published MSKCC and IMDC model HRs. Discrimination (c index) was assessed based upon the continuous scores obtained as the weighted combination of regression parameters from the published MSKCC &amp; IMDC models. Results: KPS &lt; 80% remained highly prognostic in both treatment groups (HRs &gt; 2.5). With the exception of high calcium, the other factors of time from dx to treatment &lt; 1 yr, hemoglobin &lt; lower limit of normal (LLN), neutrophils &gt; upper limit of normal (ULN), platelets &gt; ULN and LDH &gt; 1.5xULN consistently retained prognostic value for SUN (HRs ≥ published model HRs) but had diminished prognostic value for NIVO/IPI (each HR &lt; published model HR). High calcium had diminished prognostic value for SUN and retained prognostic value for NIVO/IPI. The c-indices for discrimination were 0.61 and 0.64 for the MSKCC model in the NIVO/IPI and SUN treatment groups, respectively, and were 0.63 and 0.67 for the IMDC model in the NIVO/IPI and SUN treatment groups compared to reported IMDC c-index of 0.73 (Heng 2009). (Table) Conclusions: The prognostic ability of the MSKCC and IMDC risk models is reduced with combination ICI treatment. Evaluation of additional prognostic factors and development of new risk scores are needed and this work is ongoing. [Table: see text]

Prognostic factors for overall survival in patients with clear cell metastatic renal cell carcinoma: Model development and external validation with Memorial Sloan Kettering Cancer Center model and the international metastatic renal cell carcinoma database consortium model.

To develop a new prognostic model for the overall survival of patients with clear cell metastatic renal cell carcinoma (mRCC) using Korean Renal Cancer Study Group (KRoCS) database and compared it with 2 renowned prognostic models: the Memorial Sloan Kettering Cancer Center (MSKCC) and the international metastatic renal cell carcinoma database consortium (IMDC) models.Data of 790 patients diagnosed with mRCC and receiving targeted therapy as their first-line treatment were pooled to this study. Data from 4 hospitals (n = 619) were used to develop the new model and those from other 5 hospitals (n = 171) were used for external validation. After detecting prognostic factors in multivariable Cox proportional-hazards regression analysis, patients were classified into 3 risk groups, favorable (0), intermediate (1–2), and poor (3 and more) by the number of prognostic factors.Seven variables such as more than 2 metastasis sites, no prior nephrectomy, Eastern Cooperative Oncology Group performance status ≥2, low hemoglobin, high serum corrected calcium, high neutrophil, high serum alkaline phosphatase were identified as prognostic factors for poor overall survival. Also, risk groups were categorized into 3 groups; median overall survival was 61.1 months in favorable, 26.5 months in intermediate, and 6.8 months in poor group. KRoCS ranked the first in all 3 statistical parameters including akaike information criterion (AIC), concordance index and generalized R2 among other prognostic models.We developed the KRoCS model and validated it externally with demonstrating its superiority over MSKCC and IMDC models. The KRoCS model can provide useful information for counseling patients with clear cell mRCC regarding life-expectancy.

Development of novel ACN (albumin, C-reactive protein and neutrophil-to-lymphocyte ratio) prognostication model for patients with metastatic renal cell carcinoma receiving first-line molecular-targeted therapy

PurposeThe objective of this study was to develop a novel prognostication model in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). MethodsThis study included 325 consecutive mRCC patients receiving first-line molecular-targeted therapy at 4 institutions. Potential parameters associated with overall survival (OS) in these patients were investigated to develop a novel stratification model. ResultsMedian OS of the 325 patients was 38 months. A multivariable analysis of several factors identified independent predictors associated with unfavorable OS as follows: no previous nephrectomy, Karnofsky performance status <80%, albumin (Alb) ≤3.5 g/dl, C-reactive protein (CRP) >0.5 mg/dl and neutrophil-to-lymphocyte ratio (NLR) >3. Of these 5 independent OS predictors, 3 numeric factors were used to develop the ACN (Alb, CRP, and NLR) model by dividing patients into 3 groups according to the positive numbers of these 3 numeric risk factors. Median OS durations were 63, 37, and 11 months in the favorable (n = 105, 32.3%, without risk factors), intermediate (n = 88, 27.1%, with a single risk factor), and poor (n = 132, 40.6%, with multiple risk factors) risk groups, respectively. The ACN model as a prognostication tool was shown to be superior to the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models by both the concordance index and decision curve analysis. ConclusionsThe ACN model could stratify the prognostic risk of mRCC patients receiving first-line targeted therapy more accurately than the MSKCC and IMDC models.

Prognostic Stratification of the IMDC Intermediate Risk Group After Treatment With First-line Molecular-targeted Therapy for Metastatic Renal Cell Carcinoma.

The therapeutic outcomes of patients with metastatic renal cell carcinoma (mRCC) have dramatically improved with the introduction of molecular-targeted agents. The observational multicenter study was conducted to develop a novel stratification system for the intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. The present study included 252 Japanese patients with mRCC who received first-line molecular-targeted therapy at four institutions. The 252 patients were classified into the favorable, intermediate, and poor risk groups by the IMDC model. For the intermediate risk group, multivariate analysis of the six factors included in the IMDC model revealed that a low performance status, anemia, and a high platelet count were independent predictors of poor overall survival (OS). The intermediate risk group was subsequently divided into the following two groups (int -group 1 and 2) by the three independent OS predictors. Significant differences in the OS were noted among the IMDC favorable risk group, int-group 1, int-group 2, and poor risk group. The novel stratification presented in this study could be a useful tool for further prognostication of patients with mRCC classified into the intermediate risk group according to the IMDC model after first-line molecular-targeted therapy.

Exploration of IMDC model in patients with metastatic renal cell carcinoma using targeted agents: a meta-analysis.

ABSTRACTPurpose:To explore the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model application for predicting outcome of patients with metastatic renal cell carcinoma using targeted agents.Materials and Methods:We performed a literature review of 989 articles. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). All included studies were assessed by Newcastle-Ottawa scale. Results of individual studies were pooled using Stata 14.0 software.Results:A total of 17 articles were included. Most articles provided univariate and multivariate analysis of IMDC model prognosis. Combined HRs were 1.58 (95% CI 1.34-1.82) and 3.74 (95% CI 2.67-4.81) for univariate PFS of intermediate to favorable and poor to favorable respectively. In the category of multivariate PFS, combined HRs were 1.27 (95% CI 0.99-1.56) and 2.29 (95% CI 1.65-2.93) with intermediate to favorable and poor to favorable respectively. Regarding univariate OS, combined HRs were 1.93 (95% CI 1.62-2.24) and 6.25 (95% CI 4.18-8.31) with intermediate to favorable and poor to favorable respectively. With multivariate OS, combined HRs were 1.32 (95%CI 1.04-1.59) and 2.35 (95%CI 1.69-3.01) with intermediate to favorable and poor to favorable respectively.Conclusion:In summary, analysis of currently available clinical evidence indicated that IMDC model could be applied to classify patients with metastatic renal cell carcinoma using targeted agents. However, different types of targeted agents and various areas could affect the accuracy of the model. There was also a difference in predicting patients' PFS and OS.

Inflammatory markers to predict prognosis in renal cell carcinoma (RCC) patients treated with immune checkpoint inhibitors (ICIs).

757 Background: Immune checkpoint inhibitors have increased survival in mRCC across all risk groups. In this new treatment paradigm, inflammatory markers could add prognostic information to the International metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients treated with ICI. Methods: We conducted a multicenter retrospective analysis of mRCC patients treated with ICI from 2013 to 2019. Clinical, pathological and laboratory data including blood cell counts were collected. Multivariate Cox-regression models were performed to evaluate the independent prognostic significance of the IMDC score, the derived neutrophil to lymphocyte ratio (dNLR) and LDH at baseline, as well as the inflammatory prognostic index (IPI). Results: A total of 104 patients were included. Of these, 19% were treatment-naïve, 34% had received one previous line of treatment and 47% had received two or more previous lines of treatment. Distribution of IMDC model for favorable, intermediate and poor risk was 23%,57% and 20%. Median OS was 15 months and the disease control rate (DCR) was 51%. The multivariate analysis identified the IMDC risk score, the dNLR and the IPI as independent predictors of OS. In addition, both inflammatory markers, the IPI and the dNLR, were able to improve the prognostic value of the IMDC risk score (p = 0.01 and p = 0.006, respectively). Specifically, in patients with 0 or 1 IMDC risk factors, both the IPI and the dNLR were able to subclassify additional prognostic subgroups (i.e. dNLR &gt; 3 vs ≤3 HR = 3,16; 95% CI; 1.71-5.76). Conclusions: Adding IPI and/or dNLR may add further information about the benefit of ICIs in mRCC patients with 0 or 1 IMDC risk factors. Inflammatory systemic markers may improve the prognostic performance of the IMDC model.[Table: see text]

Impact of the systemic immune-inflammation index for the prediction of prognosis and modification of the risk model in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because many of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC, and its usefulness for re-classification of patients with a more sophisticated risk model. From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared. The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively. The SII is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.

Novel Predictive Models of Early Death Less Than 1 Year in Patients With Metastatic Renal Cell Carcinoma After Treatment With First-line Tyrosine Kinase Inhibitors.

We aimed to develop a modified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model that can predict early death less than 1 year in patients with metastatic renal cell carcinoma (mRCC) after receiving first-line tyrosine kinase inhibitors (TKIs). We retrospectively reviewed records of patients with mRCC treated with first-line TKIs at our institution between 2007 and 2012. The primary endpoint was the rate of early death within 1 year after first-line TKI administration. We determined statistically significant factors predicting early death by performing multiple logistic regression. The modified IMDC model 1 was developed using new variables in addition to the risk criteria of the IMDC model, and model 2 was developed using new variables irrespective of the risk classification of IMDC model. Early mortality within 1 year of first-line TKI treatment was 19.7% (n= 98) in 462 patients. Although the C-index of the IMDC model for early death was 0.655, the C-index of model 1, which includes 5 variables (previous nephrectomy, body mass index, multiple metastases, previous metastasectomy, and serum albumin level) in addition to the Heng criteria, was 0.823. The C-index of model 2, which includes 7 variables (hemoglobin, neutrophil level, and the 5 variables of model 1) was 0.822. Of note, there was no significant difference in net reclassification index between the 2 models. This is the first study suggesting novel prediction models for early death less than 1 year in patients with mRCC treated with first-line TKI.

Validation of the IMDC Prognostic Model in Patients With Metastatic Renal-Cell Carcinoma Treated With First-Line Axitinib: A Multicenter Retrospective Study.

The objective of the study was to validate the characteristics of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model in patients treated with first-line axitinib in clinical practice. We retrospectively evaluated 143 patients with metastatic renal-cell carcinoma who were treated with axitinib as the first-line therapy between October 2008 and February 2019. Overall survival (OS) was evaluated according to the IMDC prognostic model. We investigated the intragroup heterogeneity in the intermediate-risk group and divided these patients according to abnormal C-reactive protein (CRP) levels. An inverse probability of treatment-weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate the effects of the CRP-risk model of OS in the patients in the IMDC intermediate-risk group. A significant difference in OS was observed in patients in the IMDC intermediate- and poor-risk group, although no significant difference was observed between the IMDC favorable- and intermediate-risk group. Significantly shorter prognosis was observed in patients in the IMDC intermediate-risk group who had 2 risk factors and CRP≥0.3 mg/dL (inter-high group) than in those with 1 risk factor or 2 risk factors with CRP<0.3 mg/dL (inter-low group). IPTW-adjusted Cox regression analysis revealed significant differences in the OS between the inter-low and inter-high groups. The IMDC prognostic model was active in patients who received first-line axitinib treatment. The combination of CRP value with the number of positive risk factors in the IMDC model might predict prognosis in patients with IMDC intermediate-risk treated with first-line axitinib.

Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics. Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman's correlation coefficient. Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399-3.966, p = 0.001; and HR 1.994; 95% CI 1.360-2.923, p < 0.001, respectively). In our cohort, α1-globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α1-globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001). High serum α1-globulin correlates with high tumor load. Serum α1-globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.

Impact of disagreement between the IMDC and MSKCC risk groups on prognosis in patients with metastatic renal cell carcinoma.

556 Background: As the clinical implication of the risk group disagreement between the risk models remains unclear, we aimed to investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis. Methods: We retrospectively evaluated 176 patients with metastatic renal cell carcinoma (mRCC) who were treated with tyrosine kinase inhibitors as first-line therapy in five hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the MSKCC and IMDC models was evaluated using Cohen’s k coefficient. Oncological outcomes were compared between the agreement and disagreement groups. Results: The number of patients with agreement, upgrade, and downgrade was 135/176 (77%), 39/176 (22%), and 2/176 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor-risk group was most frequent (n = 34/176, 19%). The Cohen’s k coefficient for agreement of the two risk models was substantial with k value of 0.613 ( P &lt; 0.001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Conclusions: Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with mRCC. Further study is necessary to validate our findings.

Impact of Disagreement Between Two Risk Group Models on Prognosis in Patients With Metastatic Renal-Cell Carcinoma.

To investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis. We retrospectively evaluated 176 patients with metastatic renal-cell carcinoma who were treated with tyrosine kinase inhibitors as first-line therapy in 5 hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the models was evaluated using the Cohen κ coefficient. Oncologic outcomes were compared between the agreement and disagreement groups. The number of patients with agreement, upgrade, and downgrade was 135 (77%), 39 (22%), and 2 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor risk group was most frequent (n= 34, 19%). The Cohen κ coefficient for agreement was substantial, with κ= 0.613 (P< .001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Neutrophil count, hemoglobin, serum calcium concentration, and C-reactive protein were significantly different between the groups. Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with metastatic renal-cell carcinoma. The inclusion of systematic inflammation markers in a risk model may be essential for prognosis prediction.

Comparison of three risk stratification models for non-clear cell renal cell carcinoma patients treated with temsirolimus as first-line therapy

Background/AimsFor metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus.MethodsThis study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed.ResultsTwenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%).ConclusionsAll three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Application of the International Metastatic Renal Cell Carcinoma Database Consortium and Memorial Sloan Kettering Cancer Center Risk Models in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multi-Institutional Retrospective Study Using the Korean Metastatic Renal Cell Carcinoma Registry.

PurposeThe International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were developed predominantly with clear cell renal cell carcinoma (RCC). Accordingly, whether these two models could be applied to metastatic non-clear cell RCC (mNCCRCC) as well has not been well-known and was investigated herein.Materials and MethodsFrom the Korean metastatic RCC registry, a total of 156 patients (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both models were applied to predict first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS).ResultsThe median first-line PFS, total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model reliably discriminated three risk groups to predict survival: the median first-line PFS, total PFS, and CSS for the favorable, intermediate, and poor risk groups were 9, 5, and, 2 months (p=0.001); 14, 7, and 2 months (p < 0.001); and 41, 21, and 8 months (p < 0.001), all respectively. The MSKCC risk model also reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.005); 10, 7, and 3 months (p=0.002); and 50, 21, and 8 months (p < 0.001), also all respectively. The concordance indices were 0.632 with the IMDC model and 0.643 with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS.ConclusionThe current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS, and CSS in mNCCRCC.