scholarly journals Significance of upfront cytoreductive nephrectomy stratified by IMDC risk for metastatic renal cell carcinoma in targeted therapy era – a multi-institutional retrospective study

2022 ◽  
Author(s):  
Renpei Kato ◽  
Sei Naito ◽  
Kazuyuki Numakura ◽  
Shingo Hatakeyama ◽  
Tomoyuki Koguchi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Cox Regression ◽  
Time Varying ◽  
Intermediate Risk ◽  
Cytoreductive Nephrectomy ◽  
Poor Risk ◽  
Time Varying Covariates

Abstract Background This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. Methods We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. Results Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29–0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11–0.59, p < 0.01). Conclusions Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

Subclassification of the intermediate-risk group in patients with advanced renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16537-e16537
Author(s):  
Maria Zapata-Garcia ◽  
Maria Zurera Berjaga ◽  
Alba Moratiel Pellitero ◽  
Marta Gascon Ruiz ◽  
Andrea Sesma Goñi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Intermediate Risk ◽  
First Line ◽  
Poor Risk ◽  
Prognosis Group

e16537 Background: Renal cell carcinoma (RCC) have low prevalence but it incidence is increasing. For a correct therapeutic approach, it is important to carry out a correct prognostic stratification. Several prognostication systems have been proposed. One of the most commonly used is the one developed by Heng. It is based on IMDC database. This classification includes six prognostic factors (hemoglobin, neutrohils, platelets, serum calcium, Karnosky Performance Status and time from diagnosis to initiaton treatment) to divide patients into three gorups. The relevance of IMDC prognostic criterio, in the era of immunotherapy, remains to be established. In the absence of alternative criteria, these prognostication system continue to be used. A great prognostic disparity has been observed in the intermediate prognosis group. This raises the need to divide this group into two. Thus, patients included in it would be better selected. Methods: Observational, single-center, retrospective study, based on a cohort of 107 patients with advanced RCC, recruited from January 2006 to December 2019. Main objective: Evaluate whether survival of patients with intermediate prognosis (treated with antiangiogenic in first-line) is different depending on the presence of one or two prognostic factors. Descriptive and survival analysis (OS and PFS) were performed. In addition, the influence of prognostic factors on OS and PFS were compared using the log-rank test and Cox regression. Results: In the overall population, median overall survival (OS) was 26.86 months (95% CI: 21.09-32.63) and median PFS was 18.41 months (95% CI: 14.02-22.79). Median OS were, in favorable-risk 42.24 months (95% CI: 29.62-54.62), in intermediate-risk 27,24 (95% CI: 19.44-35-03) and in poor-risk 8.00 (95% CI: 4.54-11.45). Median PFS were in favorable-risk 30.53 months (95% CI:20.92-40.13), in intermediate-risk 17,16 (95% CI:11.54-22.78) and poor-risk 6.13 (95% CI:3.02-9.25). Median OS and PFS, in patients with intermediate-risk, with a single risk factor were 33.79 (95% CI 23.17-44.41) and 20.97 months (95% CI 13.35-28.59), compared to 14.88 (95% CI 8.80-20.95) and 10.59 months (95% CI 4.87-16.32) in those with two risk factors. The results were statistically significant in OS (p = 0.01) and PFS (p = 0.037). Conclusions: The differences in median OS and PFS, within the intermediate prognosis group (1 or 2 RF), confirm the existence of two subgroups of patients. Patients with 1 RF are similar to those with favorable-risk. These results are important since, the presence of 1 or 2 RF, would condition the choice of TKIs as part of the first-line treatment combination. More studies are needed to better subclassify the intermediate risk group when optimizing the best treatments for each patient.

Serum Lactate Dehydrogenase Predicts for Overall Survival Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Inhibition of Mammalian Target of Rapamycin

2012 ◽  
Vol 30 (27) ◽  
pp. 3402-3407 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Daniel J. George ◽  
Susan Halabi
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Lactate Dehydrogenase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Mammalian Target Of Rapamycin ◽  
Phase Iii ◽  
Target Of Rapamycin ◽  
Poor Risk

Purpose Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)–containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. High serum LDH levels are associated with poor prognosis in patients with cancer, including renal cell carcinoma (RCC). We tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC receiving an mTOR inhibitor. Patients and Methods We evaluated pretreatment and post-treatment serum LDH in 404 poor-risk patients with RCC treated with the TORC1 inhibitor temsirolimus or interferon alfa in an international phase III randomized trial. The proportional hazards model was used to test for the prognostic and predictive association of LDH in predicting overall survival (OS). Results Mean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN; range, 0.05 to 28.5 × ULN). The multivariable hazard ratio for death was 2.81 (95% CI, 2.01 to 3.94; P < .001) for patients with LDH more than 1 × ULN versus patients with LDH ≤ 1 × ULN. The LDH-treatment interaction term was statistically significant for OS (P = .016). Among 140 patients with LDH above the ULN, OS was significantly improved with temsirolimus (6.9 v 4.2 months; P < .002). Among 264 patients with normal LDH, OS was not significantly improved with temsirolimus as compared with interferon therapy (11.7 v 10.4 months; P = .514). Conclusion Serum LDH is a prognostic and a predictive biomarker for the survival benefit conferred by TORC1 inhibition in poor-risk RCC. Further investigation of the predictive role of LDH as a measure of benefit with PI3K/TORC1 pathway inhibition in other RCC risk groups and other tumor types is warranted.

scholarly journals Metastatic renal cell carcinoma patients of T4 stage who are in status of N1 stage or older than 76 years cannot benefit from Cytoreductive Nephrectomy

2020 ◽  
Author(s):  
Zhao Zhang ◽  
Hongliang Wu ◽  
Tong Yang ◽  
Yaohai Wu ◽  
Nengwang Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Subgroup Analysis ◽  
Renal Cell ◽  
Survival Benefit ◽  
Cox Regression ◽  
Seer Database ◽  
Cytoreductive Nephrectomy ◽  
Cox Regression Analysis ◽  
T4 Stage

Abstract Background: We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN).Methods: The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan–Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots. Results: The records of 21411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age≥76yr subgroups could not obtain survival benefit from CN.Conclusion: CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them.

Checkpoint inhibitors in metastatic renal cell carcinoma patients including elderly subgroups: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Steven Yip ◽  
Connor Wells ◽  
Raphael Brandao Moreira ◽  
Alex Wong ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cox Regression ◽  
Cell Cancer ◽  
Second Line ◽  
Cox Regression Analysis ◽  
Poor Risk

4580 Background: Immuno-oncology (IO) checkpoint inhibitor treatment outcomes are poorly characterized in the real world metastatic renal cell cancer (mRCC) patient population, including geriatric patients. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with IO, as listed below. Patients received one or more lines of IO therapy, with or without a targeted agent. Duration of treatment (DOT) and overall response rates (ORR) were calculated. Cox regression analysis was performed to examine the association between age as a continuous variable and DOT. Results: 312 mRCC patients treated with IO were included. In patients who were evaluable, ORR to IO therapy was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line treatment (Tx)). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median DOT rates were not reached (NR), 8.6 mo, and 1.9 mo, respectively (p<0.0001). Based upon age, hazard ratios were calculated in the first- through fourth-line therapy setting, ranging from 1.03 to 0.97. Conclusions: The ORR to IO appears to remain consistent, regardless of line of therapy. In the second-line, IMDC criteria appear to appropriately stratify patients into favorable, intermediate, and poor risk groups for DOT. Premature OS data will be updated. In contrast to clinical trial data, longer DOT is observed in real world practice. Age may not be a factor influencing DOT. [Table: see text]

The role of cytoreductive nephrectomy in elderly patients with metastatic renal cell carcinoma in an era of targeted therapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 499-499
Author(s):  
Dipesh Uprety ◽  
Amir Bista ◽  
Yazhini Vallatharasu ◽  
David E. Marinier
Keyword(s):  
Renal Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Performance Status ◽  
Cytoreductive Nephrectomy ◽  
Significant Survival

499 Background: The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) has not been clearly understood after the approval of new targeted therapies, particularly in an elderly population. We therefore conducted this study to evaluate survival difference (CN vs. no CN) among elderly patients with mRCC in targeted era. To limit the heterogeneity in use of targeted agents we define targeted era as February 2006 to December 2011, as sunitinib got FDA approval for use in RCC in January 2006. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER-18) database to identify elderly (≥ 65 years) patients with mRCC, as first primary malignancy, who were diagnosed between February 2006 and 2011. Kaplan-Meier curve and log rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between patients receiving CN and not receiving CN. Cox proportional hazard model was used for multivariate analysis. Results: Out of 3,365 patients, 1088 (32.3%) received CN. There was a significant survival benefit for those who received CN vs. those who did not (Median OS: 22 months vs. 5 months, p< 0.001; Median CSS: 25 months vs. 6 months, p<0.001). After adjusting for age, sex, race, T-stage, N-stage, histology types, and year of diagnosis, patient receiving CN had significantly better 3-year OS and 3-year CSS compared to patients not receiving CN with HR of 0.37, 95% CI of 0.34 to 0.41; p<0.001 and HR of 0.37, 95% CI of 0.34 to 0.42, p <0.001 respectively. Among patients who received CN, younger age at diagnosis, other races (other than Caucasian and African American), and N0 stage were found to be independent factors predicting better survival. Conclusions: SEER database lacks individual patient’s information. One may argue that the non-surgical group may have larger proportion of patients with poor performance status. Despite this limitation, our study showed that CN has significant survival benefit and should be a serious consideration in elderly patients if they have good performance status.

Deferred cytoreductive nephrectomy among patients with newly diagnosed metastatic renal cell carcinoma treated initially with sunitinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bimal Bhindi ◽  
Jeffrey Graham ◽  
Connor Wells ◽  
Frede Donskov ◽  
Felice Pasini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Multivariable Analysis ◽  
Newly Diagnosed ◽  
Cytoreductive Nephrectomy ◽  
Immortal Time Bias

4578 Background: While the CARMENA trial prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC), 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential litmus test to identify patients suitable for CN, but data on outcomes are limited. We sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone. Methods: Patients with newly diagnosed mRCC receiving upfront sunitinib were identified from the International mRCC Database Consortium (IMDC) from 2006-2018. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes were overall survival (OS) and time to treatment failure (TTF). Kaplan Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results: The cohort included 708 patients of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib (Table). There were 604 deaths during a median follow-up of 63 months. Median OS and TTF with dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months without, respectively. Upon multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p < 0.001) but not TTF (HR 0.73, 95%CI 0.52-1.01; p = 0.056). Conclusions: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. [Table: see text]

scholarly journals Metastatic renal cell carcinoma patients of T4 stage who are in status of N1 stage or older than 76 years cannot benefit from Cytoreductive Nephrectomy

2020 ◽  
Author(s):  
Zhao Zhang ◽  
Hongliang Wu ◽  
Tong Yang ◽  
Yaohai Wu ◽  
Nengwang Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Subgroup Analysis ◽  
Renal Cell ◽  
Survival Benefit ◽  
Cox Regression ◽  
Seer Database ◽  
Cytoreductive Nephrectomy ◽  
Cox Regression Analysis ◽  
T4 Stage

Abstract Background: We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN).Methods: The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan–Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots.Results: The records of 21411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age≥76yr subgroups could not obtain survival benefit from CN.Conclusion: CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them.

scholarly journals The role of cytoreductive nephrectomy in renal cell carcinoma patients with liver metastasis

2020 ◽  
Author(s):  
Boda Guo ◽  
Shengjing Liu ◽  
Miao Wang ◽  
Huimin Hou ◽  
Ming Liu
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Propensity Score ◽  
Cell Carcinoma ◽  
Propensity Score Matching ◽  
Renal Cell ◽  
Cox Regression ◽  
Cytoreductive Nephrectomy ◽  
Dismal Prognosis

It is widely accepted that renal cell carcinoma with liver metastasis carries a dismal prognosis. We aimed to explore the value of cytoreductive nephrectomy among these patients. Patients were extracted from the SEER database between 2010 and 2017. The univariate and multivariate Cox proportional hazards models were conducted to select the prognostic predictors of survival. Patients were divided into nephrectomy and non-nephrectomy groups. Propensity score-matching analyses were applied to reduce the above factors’ differences between the groups. Overall survival was compared by Kaplan-Meier (K-M) analyses. Data from 683 patients was extracted from the database. The univariate Cox regression and multivariate Cox regression revealed that factors including age, histologic type, T and N stages, lung metastasis, brain metastasis, and nephrectomy were significant predictors of survival in the patients. After the propensity score-matching analyses, we found that nephrectomy prolonged overall survival. Nephrectomy can prolong overall survival in eligible renal cell carcinoma patients with liver metastasis.

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