Cytoreductive Nephrectomy Group Research Articles

Cytoreductive nephrectomy and its effect on prognosis in patients with disseminated renal cell carcinoma receiving treatment in wide clinical practice

Aim. To evaluate the effect of cytoreductive nephrectomy (CN) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to identify a group of patients who are candidates for cytoreductive surgical treatment.Materials and methods. We retrospectively analyzed a database of 403 patients with mRCC treated at the Moscow City Oncological Hospital No. 62 and the City Clinical Oncological Dispensary (Saint Petersburg) between 2006 and 2022. In total, 330 (81.9 %) patients underwent CN. All patients received systemic anti-tumor therapy: targeted anti-angiogenic therapy - 317 (78.6 %), cytokines - 61 (15.1 %), checkpoint inhibitors - 25 (6.2 %). The groups of operated and non-operated patients were unbalanced: CN was more often not performed in patients with multiple metastases, bone and liver lesions, laboratory abnormalities (anemia, increased serum alkaline phosphatase and lactate dehydrogenase) and unfavorable prognosis per IMDC (International mRCC Database Consortium) classification (p >0.05 for all). Results. CN was associated with a significant increase in OS compared with primary tumor preservation in situ: median OS was 36 months with 95 % confidence interval 29.1-37.1, and 11 months with 95 % confidence interval 8.1-21.3, respectively (p <0.0001). The benefit for OS in the CN group was also observed in clear-cell mRCC (p <0.0001), grade G3 (p <0.0001), multiple metastases (p <0.0001) groups, and in the IMDC poor prognosis group (p <0.0001). Conclusion. CN in selected mRCC patients results in a significant increase in OS. Further research is needed to determine selection criteria for surgical treatment candidates.

Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma.

The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.

PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL

You have accessJournal of UrologyCME1 Apr 2023PD17-04 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY WITH IMMUNE CHECKPOINT INHIBITOR THERAPIES IN METASTATIC RENAL CELL CARCINOMA MURINE MODEL Jee Soo Park, Myung Eun Lee, Won Sik Jang, Jongchan Kim, Se Mi Park, and Won Sik Ham Jee Soo ParkJee Soo Park More articles by this author , Myung Eun LeeMyung Eun Lee More articles by this author , Won Sik JangWon Sik Jang More articles by this author , Jongchan KimJongchan Kim More articles by this author , Se Mi ParkSe Mi Park More articles by this author , and Won Sik HamWon Sik Ham More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since CARMENA trial found non-inferiority of sunitinib alone, the contemporary role of cytoreductive nephrectomy (CN) has been significantly downsized. However, updated CARMENA trial results demonstrated certain subsets with metastatic renal cell carcinoma (mRCC) may still benefit from CN. We tried to assess the role of CN in combination with immune checkpoint inhibitor (ICI) from the perspective tumor immune microenvironment (TIME). METHODS: Low- and high-tumor burden pulmonary metastatic orthotopic murine mRCC models have been developed. Anti-PD-1 and anti-CTLA-4 antibodies were systemically injected through the peritoneum every 3 days. Renca implanted kidney was removed in the CN performed group. For the upfront CN plus ICI group, CN was performed 1 day before the ICI, while CN was performed 5 days after ICI for the deferred CN plus ICI group. The remodeling of the TIME was determined using immunofluorescence analysis. RESULTS: Low- and high-tumor burden murine mRCC models have been successfully developed with statistically significant difference in median survival (p<0.05). In low-tumor burden model (Figure 1A), upfront CN plus ICI group demonstrated significantly better survival outcomes compared to deferred CN plus ICI group. In high-tumor burden model (Figure 1B), similar results were shown as low-tumor burden model, except no significant survival difference between ICI only and CN only group, and between upfront CN plus ICI and deferred CN plus ICI group. Immunofluorescence analysis demonstrated that CN modulate TIME by increasing M1 tumor-associated macrophage (TAM) and at the same time decreasing M2 TAM (Figure 2). CONCLUSIONS: This study is the first animal study to demonstrate the role of CN in combination with ICI. We have shown that the CN has certain role in the immune-oncology (IO) era and was associated with improved survival by the regulation of M1 and M2 TAM. CN also regulated myeloid-derived suppressor cells and regulatory T cells in combination with ICIs although not to be significant in our study. Source of Funding: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI17C1095], and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number: 2019R1A2C1002863 and 2022R1A2C2003831] © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e496 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jee Soo Park More articles by this author Myung Eun Lee More articles by this author Won Sik Jang More articles by this author Jongchan Kim More articles by this author Se Mi Park More articles by this author Won Sik Ham More articles by this author Expand All Advertisement PDF downloadLoading ...

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in the targeted therapy and immunological therapy era: a systematic review and meta-analysis.

The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains controversial. In addition, several unanswered questions regarding the use of CN remain: Can CN provide survival benefits for patients with mRCC? Where do we place CN in the treatment sequence paradigm among patients with mRCC? How do we best stratify patients with mRCC for CN therapy? A search strategy was conducted in the PubMed, Embase, and Web of Science databases. Studies were included only in the English language. The risk of bias assessment was made by using ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) and RoB 2 (Risk of Bias 2) tools. The expected outcomes were analyzed by meta-analyses with the fixed-effects model or random effects model, including overall survival (OS) and progression-free survival (PFS). The measure of effect was the hazard ratio (HR) with a 95% CI, and sensitivity analysis was conducted to assess the reliability of the final results. A total of 30 studies were included in the qualitative analysis. The HR for OS was 0.55 (95% CI, 0.50-0.61), and PFS was 0.72 (95% CI, 0.66-0.80), favoring CN compared with no CN. The upfront CN plus targeted therapy (TT) group had superior OS (HR, 0.57; 95% CI, 0.51-0.64) compared with the TT alone group. Furthermore, upfront CN plus systemic therapy (ST) was associated with numerically inferior OS compared with ST plus deferred CN in patients with mRCC (HR, 1.31; 95% CI, 0.98-1.74). Finally, the leave-one-out test of sensitivity analysis indicated that the results of this meta-analysis were stable and reliable in the overall HR estimates for these survival outcomes. First, CN was associated with better survival than no CN in patients with mRCC. Second, the combination of upfront CN and TT may lead to superior survival outcomes compared to TT alone in patients with mRCC. Survival outcomes were similar between the upfront CN+ST group and the ST+deferred CN group in patients with mRCC. Exact patient selection based on baseline prognostic factors is needed to promise maximal survival for patients with mRCC.

The impact of cytoreductive nephrectomy on survival outcomes in patients with metastatic renal cell carcinoma receiving immunotherapy: An evidence-based analysis of comparative outcomes.

The prognostic impact of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immunotherapy is yet to be determined. The aim of our study is to evaluate the correlation between CN and outcomes in the setting of mRCC treated with immunotherapy. We conducted a systematic search of the Science, PubMed, Web of Science, and Cochrane Library databases to identify relevant studies published in English up to December 2022. The results were presented as hazard ratio (HR) with 95% confidence intervals (CIs) for overall survival (OS) was extracted to assess their relevance. The study was registered with PROSPERO (CRD42022383026). A total of 2397 patients were included in eight studies. The CN group was observed to be correlated with superior OS compared to the No CN group (HR = 0.53, 95% CI 0.39-0.71, p < 0.0001). Subgroup analysis according to the type of immunotherapy, sample size, and treatment line of immune checkpoint inhibitor revealed that CN group had a superior OS in all subgroups. CN is associated with a better outcome in terms of OS benefit in selected patients with mRCC treated by immunotherapy, but further studies are required to verify the conclusions. https://www.crd.york.ac.uk/prospero/, identifier CRD42022383026.

Advantages of organ-sparing treatment approaches in metastatic kidney cancer.

This study analyzed oncological outcomes of patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with cytoreductive partial nephrectomy or nephrectomy. This prospective non-randomized cohort study included 109 patients with metastatic ccRCC who underwent surgical treatment between 2011 and 2020. Patients were stratified into cytoreductive partial nephrectomy or nephrectomy groups. Survival curves were estimated, and Cox-regression analysis was performed to identify factors affecting potential lethality. The groups differed significantly in terms of T stage and International metastatic RCC database consortium (IMDC) risk groups, but not international society of urological pathology (ISUP) grading. The average blood loss volume was higher in the partial nephrectomy group. In contrast, the duration of post-operative stay, complication rate; and 30-day hospital readmission rate were similar between two groups. There was a significant difference in overall survival in favor of the partial nephrectomy group, who had better 7-year survival rates. Standardization based on the clinical complexity of the patients showed that cytoreductive partial nephrectomy was associated with a lower risk of death compared to nephrectomy. Partial nephrectomy is a safe method of choice in patients with metastatic ccRCC. Kidney preservation in a metastatic setting can play a role in reducing potential adverse systemic therapy events and in decreasing the risk for concomitant pathology deterioration.

A comparison of cytoreductive and non-cytoreductive management strategies for nephron-sparing approaches to tumours in solitary kidneys.

Tumours in a solitary kidney pose challenges in management. Metastatic tumours and those in difficult locations complicate treatment further. The advent of immunotherapy has shed new light on the management of such tumours. We present a series of three cases treated with nephron-sparing surgery following neoadjuvant immunotherapy and compare the outcomes with patients who underwent robotic partial nephrectomy in a solitary kidney. We present the outcomes of three patients with solitary kidney tumours who underwent delayed nephron-sparing surgery following good response to immunotherapy. All patients had solitary kidney following a previous nephrectomy, two of which were nonmetastatic but, due to size/location, not amenable to primary treatment; the third patient had metastatic disease and responded to immunotherapy. Two patients underwent robotic partial nephrectomy and one opted for cryotherapy. We compared the preoperative, intraoperative and postoperative parameters of the two patients who underwent robotic cytoreductive partial with patients who underwent robotic partial nephrectomy in a solitary kidney. Out of 231 partial nephrectomy patients in our centre, 2 underwent cytoreductive partial nephrectomy and 5 underwent solitary partial nephrectomy. There was no statistically significant difference in the patient demographics in the two groups. Patients in both groups had comparable operative time, warm ischaemia time, blood loss and length of stay. Two of the five patients in the non-cytoreductive robotic partial nephrectomy had Clavien Dindo1 complications compared with one patient in the robotic cytoreductive partial nephrectomy group. This was not statically significant. Neoadjuvant immunotherapy can play a valuable role in shrinking renal tumours in solitary kidneys to facilitate robotic partial nephrectomies. There were no significant differences in the intra- and postoperative parameters in patients who underwent cytoreductive partial nephrectomy when compared with patients undergoing robotic solitary partial nephrectomy.

MP12-09 PROGNOSTIC MODEL OF UPFRONT CYTOREDUCTIVE NEPHRECTOMY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH IMMUNE-CHECKPOINT INHIBITORS AND/OR TYROSINE KINASE INHIBITORS

You have accessJournal of UrologyCME1 May 2022MP12-09 PROGNOSTIC MODEL OF UPFRONT CYTOREDUCTIVE NEPHRECTOMY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH IMMUNE-CHECKPOINT INHIBITORS AND/OR TYROSINE KINASE INHIBITORS Jun Teishima, Keisuke Goto, Yohei Sekino, Tetsutaro Hayashi, and Nobuyuki Hinata Jun TeishimaJun Teishima More articles by this author , Keisuke GotoKeisuke Goto More articles by this author , Yohei SekinoYohei Sekino More articles by this author , Tetsutaro HayashiTetsutaro Hayashi More articles by this author , and Nobuyuki HinataNobuyuki Hinata More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002534.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to investigate the prognostic factor and to establish the prognostic model using them of upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). METHODS: Four hundred patents with mRCC treated with TKI and/or ICI were classified into 3 groups; those undergoing CN (upfront CN group, 117 cases), those who initially underwent systemic therapy (non-upfront CN group, 94 cases), and those whose recurrence were pointed out after radical nephrectomy (RN) (RN group, 189 cases). In upfront CN group, patients’ background and overall survival (OS) was compared with those in other two groups, and prognostic factors were analyzed. Prognostic model of upfront CN group was established. RESULTS: Median of the observation period in upfront CN group was 25 months. The rate of patients with clear cell histology, Karnofsky performance status (KPS) ≥80%, single metastatic organ, normal pretreated C-reactive protein level and intermediate risk in IMDC model were significantly higher than those in non-CN group (87.2% and 30.9%, p <0.0001; 92.3% and 77.7%, p=0.0025; 41.9% and 24.5%, p=0.0080, 47.9% and 13.8%, p <0.0001; 66.7% and 45.7%, p=0.0023, respectively). 50%OS in upfront CN group was 33.1months, significantly better than that in non-upfront CN group (11.1 months, p <0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and KPS <80% were independent predictive factors for OS (Hazard ratio; 1.653 and 2.995, p=0.0339 and 0.0054, respectively). Using these two parameters to stratify upfront CN group, 50%OS in cases with no risk factor, that with one factor and that with two factors were 43.4 months, 29.1 months, and 7.7 months, respectively (p <0.0001). CONCLUSIONS: Upfront CN group is able to be stratified by our prognostic model into three subgroups with different prognosis. This model can provide us useful information for making a decision of considering upfront CN in patients with mRCC. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e169 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jun Teishima More articles by this author Keisuke Goto More articles by this author Yohei Sekino More articles by this author Tetsutaro Hayashi More articles by this author Nobuyuki Hinata More articles by this author Expand All Advertisement PDF DownloadLoading ...

Shifting role of cytoreductive nephrectomy according to type of systemic therapy: A nationwide cohort study

The best protocol of cytoreductive nephrectomy (CN) and systemic therapy (ST) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear. We sought to evaluate overall survival (OS) in patients with mRCC treated with ST with or without CN. We collected data from the National Health Insurance Service database. We excluded 2 years of washout period, 2 years of follow-up period, other cancer diagnoses within 2 years, and ≥4 months interval between ST and CN. The patients were divided into two groups according to whether CN was performed. Kaplan-Meier, propensity score matching, Cox regression model, and incremental survival analyses were conducted. Additionally, we performed subgroup analysis according to whether cytokine therapy or targeted therapy was used as first-line ST. Of 6478 patients, 1707 (26.4%) underwent CN. The CN group showed significantly better OS than the no CN group (p<0.001). In the cytokine therapy subgroup, patients who underwent CN had significantly higher OS than those who did not (p<0.001). In the targeted therapy subgroup, no significant difference was found (p=0.867). In multivariate analysis, CN was associated with better OS in the total cohort (hazard ratio 0.819, p<0.001). The incremental OS benefit of CN ranged from+0.98 in patients who survived for <24 months to+2.13 in those who survived during all periods. About a quarter patients with mRCC from a nationwide database were treated with CN and ST. CN was beneficial in specific patients with mRCC. Patient selection is crucial for obtaining the benefits of CN.

Prognostic model of upfront cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors and/or targeted agents.

The aim of this study was to investigate prognostic factors and to establish a prognostic model using them for upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). Two hundred eleven patients who were diagnosed as mRCC at initial diagnosis and were treated with TKI and/or ICI were classified into 2 groups: those undergoing CN (upfront CN group, 117 cases) and those who initially underwent systemic therapy (non-upfront CN group, 94 cases). In the upfront CN group, the patients' background and overall survival (OS) were compared with those in the other two groups, and prognostic factors were analyzed. A prognostic model of the upfront CN group was established. The median of the observation period for the upfront CN group was 25months. The rates of patients with clear cell histology, with a Karnofsky performance status (KPS) of ≥ 80%, with a single metastatic organ, with a normal pretreated C-reactive protein level, and with an intermediate risk according to the International mRCC Database Consortium (IMDC) model were significantly higher than those in the non-upfront CN group (87.2% and 30.9%, p < 0.0001; 92.3% and 77.7%, p = 0.0025; 41.9% and 24.5%, p = 0.0080; 47.9% and 13.8%, p < 0.0001; 66.7% and 45.7%, p = 0.0023, respectively). The 50% OS in the upfront CN group was 33.1months, significantly better than that in the non-upfront CN group (11.1months, p < 0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and a KPS of < 80% were independent predictive factors for OS (hazard ratio: 1.653 and 2.995, p = 0.0339 and 0.0054, respectively). Using these two parameters to stratify the upfront CN group, the 50% OSs in cases with no risk factors, in those with one factor, and in those with two factors were 43.4months, 29.1months, and 7.7months, respectively (p < 0.0001). The upfront CN group was able to be stratified by our prognostic model into three subgroups with different prognoses. This model can provide useful information for making decisions in consideration of upfront CN in patients with mRCC.

Predictors of objective response to first-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Results from the international metastatic renal cell database consortium (IMDC).

310 Background: Predictors of objective response to first-line (1L) immuno-oncology (IO) combination therapies remain elusive. We sought to characterise clinical variables and their association with investigator assessed best overall response. Methods: Using the IMDC, we retrospectively identified patients treated with 1L ipilimumab nivolumab (IPI-NIVO) or approved IO/vascular endothelial growth factor (VEGF) inhibitor combinations (IOVE). Patients were classified, per RECIST v1.1, as responders (complete or partial response (CR or PR)) or non-responders (stable or progressive disease (SD or PD)). Logistic regression was used to adjust for IMDC criteria. Results: Out of 1084 patients, 794 (73%) received IPI-NIVO and 290 (27%) received IOVE (axitinib+pembrolizumab, cabozantinib+nivolumab, axitinib+avelumab, lenvatinib+pembrolizumab). Favourable, intermediate and poor IMDC risk comprised 147 (16%), 517 (55%) and 272 (29%) respectively. Of the 898 patients with evaluable responses, 37 (4%) achieved a best response of CR, 343 (38%) PR, 315 (35%) SD and 203 (23%) PD. Corresponding median overall survival from time of 1L initiation was: not reached, 55.9, 48.1, and 13 months respectively (logrank p &lt; 0.0001). In a multivariable model, lung metastases and cytoreductive nephrectomy (CN) (performed after diagnosis of metastatic disease and before 1L therapy) retained independent association with response, after adjustment for IMDC criteria. Factors not associated with response included (with univariable p values): gender (p = 0.58), age (p = 0.06), sarcomatoid histology (p = 0.99), smoking status (p = 0.39), liver (p = 0.63) and brain (p = 0.12) metastases. As in the VEGF monotherapy era, improved IMDC prognostic risk was associated with response. Results were similar when restricted to the IPI-NIVO cohort. Conclusions: Presence of lung metastases, CN and better IMDC risk group are associated with a higher probability of response to 1L immunotherapy combination regimens. Further work to identify reliable predictors of response to guide treatment selection and patient counselling is warranted.[Table: see text]

Selection of Optimal Candidates for Cytoreductive Nephrectomy in Patients with Metastatic Clear Cell Renal Cell Carcinoma: A Predictive Model Based on SEER Database.

BackgroundCurrently, the progress of targeted drugs in the treatment of metastatic clear cell renal cell carcinoma (mccRCC) is limited. Cytoreductive nephrectomy (CN), as an alternative treatment, can improve the prognosis of patients with metastatic renal cell carcinoma to some extent. However, it is unclear which patients would benefit from this tumor reduction operation. As a consequence, we developed a predictive model to identify patients who may well benefit from CN in terms of survival.MethodsWe identified patients with metastatic clear cell renal cell carcinoma retrospectively from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015) and classified them into surgery and non-surgery groups. Propensity score matching (PSM) was performed to balance the baseline characteristics. Patients who survived longer than the median overall survival (OS) of no-surgery group were defined as surgical-benefit patients. Then, we developed a predictive model based on preoperative characteristics using multivariable Logistic regression. Calibration curves and the area under the receiver operating characteristic (AUC) were used to evaluate the efficiency of the predictive model. The clinical value of the nomogram was assessed utilizing decision curve analysis (DCA).ResultsOur study collected 5544 patients from the SEER database, with 2352(42.4%) receiving cytoreductive surgery. Overall survival (OS) was longer in the CN group than in the non-surgery group after 1:1 propensity scoring matching (median OS: 19 months vs 7 months; hazard ratio (HR) =0.4106, P< 0.001). In the matched surgery group, 65.7% (367) patients survived more than 7 months after the operation and they were considered to benefit from CN. The predictive model performed well on both the training group (AUC=73.4%) and the validation group (AUC=71.9%) and the calibration curves indicated a high degree of consistency. The decision curve analysis curve demonstrated the clinical utility. We classified surgical patients into the beneficial group and non-beneficial group by using the predictive model, then discovered a substantial difference in OS between the two groups.ConclusionsWe developed a nomogram to select ideal mccRCC patients who might benefit from cytoreductive nephrectomy. Clinicians could make a more precise treatment strategy for mccRCC patients.

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

BackgroundThis 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.MethodsWe 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.ResultsOf 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).ConclusionsUpfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

External validation of the REMARCC model for the selection of cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma: A multicenter retrospective study

This study aims to evaluate the utility of the scoring system of the Registry for Metastatic Renal Cell Carcinoma (REMARCC) model on the overall survival (OS) of patients undergoing cytoreductive nephrectomy (CN).A total of 278 patients with primary metastatic renal cell carcinoma (mRCC) treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019 were identified. The c-index and net benefit between the REMARCC score were compared with the International mRCC Database Consortium (IMDC) score in patients with CN (CN group, n = 146). The effect of the REMARCC score on OS was compared between the CN group and patients without CN (non-CN group, n = 132) using Cox regression analysis under the propensity score-based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances.Of the 146 patients with CN, the c-index of the REMARCC model (0.60) was higher than the IMDC model (0.54). The decision curve analysis showed the advantage of REMARCC model predicting OS compared with the IMDC model. OS was significantly longer in the REMARCC low-score (0-2) than that in the high-score (3-6) among the patients with CN. IPTW-adjusted Cox regression analyses showed that OS was significantly longer in the CN group than that in the non-CN group among the patients with REMARCC low-score but was not significantly different between the groups among the patients with REMARCC high-score.The REMARCC score may be active for selecting the CN candidate in patients treated with TKIs.

MP14-17 VALIDATION OF REMARCC MODEL FOR SELECTION OF CYTOREDUCTIVE NEPHRECTOMY IN PATIENTS WITH mRCC

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-17 VALIDATION OF REMARCC MODEL FOR SELECTION OF CYTOREDUCTIVE NEPHRECTOMY IN PATIENTS WITH mRCC Shingo Hatakeyama, Sei Naito, Kazuyuki Numakura, Renpei Kato, Tomoyuki Koguchi, Takahiro Kojima, Yoshihide kawasaki, Sadafumi Kawamura, Nishiyama Hiroyuki, Akihito Ito, Yoshiyuki Kojima, Tomonori Habuch, Wataru Obara, Norihiko Tsuchiya, and Chikara Ohyama Shingo HatakeyamaShingo Hatakeyama More articles by this author , Sei NaitoSei Naito More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Renpei KatoRenpei Kato More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Takahiro KojimaTakahiro Kojima More articles by this author , Yoshihide kawasakiYoshihide kawasaki More articles by this author , Sadafumi KawamuraSadafumi Kawamura More articles by this author , Nishiyama HiroyukiNishiyama Hiroyuki More articles by this author , Akihito ItoAkihito Ito More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima More articles by this author , Tomonori HabuchTomonori Habuch More articles by this author , Wataru ObaraWataru Obara More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Selection of patients for cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) is challenging. We evaluated the utility of the scoring system of Registry for Metastatic RCC (REMARCC) model on overall survival in mRCC patients undergoing CN. METHODS: We identified a total of 278 patients with synchronous mRCC treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019 from a Michinoku mRCC multi-institutional registry. Patients were divided into two groups: CN (n=146) and non-CN (n=132) groups. We compared the c-index of the REMARCC score with the International mRCC Database Consortium (IMDC) score in the CN group (n=146). Decision curve analysis was used to compare the net benefit of the REMARCC score with the IMDC score. Overall survival was estimated using Kaplan-Meier analysis. The effect of REMARCC score on overall survival was compared between the CN and non-CN groups using Cox regression analysis under the propensity score-based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances. RESULTS: The median follow-up period was 18 (interquartile range: 9.4–35) months. Of 146 patients with CN, the C-index of the REMARCC model was slightly higher than that of the IMDC models (60% vs. 58%). Decision curve analysis showed a slight advantage of the REMARCC model predicting overall survival over the IMDC model. The net benefit was superior to all the other strategies up to 60% of threshold probabilities. Overall survival was significantly longer in the REMARCC low-score (0-2) than that of high-score (3-6), while it was not significantly different between the IMDC intermediate- and poor-risk groups. IPTW-adjusted Cox regression analyses showed that overall survival was significantly longer in the CN group than that in the non-CN group among the patients with the REMARCC low-score, but it was not significantly different between the groups among the patients with the REMARCC high-score. CONCLUSIONS: The REMARCC score was potentially active for selecting the optimal candidate of CN in patients treated with TKIs. A patient with the REMARCC low-score is a potential candidate for CN. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e259-e260 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shingo Hatakeyama More articles by this author Sei Naito More articles by this author Kazuyuki Numakura More articles by this author Renpei Kato More articles by this author Tomoyuki Koguchi More articles by this author Takahiro Kojima More articles by this author Yoshihide kawasaki More articles by this author Sadafumi Kawamura More articles by this author Nishiyama Hiroyuki More articles by this author Akihito Ito More articles by this author Yoshiyuki Kojima More articles by this author Tomonori Habuch More articles by this author Wataru Obara More articles by this author Norihiko Tsuchiya More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Loading ...

MP14-09 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY FOR METASTATIC RENAL CELL CARCINOMA IN NATIONAL HEALTH INSURANCE SERVICE

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-09 THE ROLE OF CYTOREDUCTIVE NEPHRECTOMY FOR METASTATIC RENAL CELL CARCINOMA IN NATIONAL HEALTH INSURANCE SERVICE Joonhee Gook, Jae Hun Shim, Byung Hoon Chi, Jin Wook Kim, In Ho Chang, Tae-Hyoung Kim, Soon Chul Myung, and Se Young Choi Joonhee GookJoonhee Gook More articles by this author , Jae Hun ShimJae Hun Shim More articles by this author , Byung Hoon ChiByung Hoon Chi More articles by this author , Jin Wook KimJin Wook Kim More articles by this author , In Ho ChangIn Ho Chang More articles by this author , Tae-Hyoung KimTae-Hyoung Kim More articles by this author , Soon Chul MyungSoon Chul Myung More articles by this author , and Se Young ChoiSe Young Choi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare the survival outcomes between patients with metastatic renal cell carcinoma (RCC) treated with cytoreductive nephrectomy (CN) and without CN. METHODS: We evaluated the National Health Insurance Service Database diagnosed with RCC between 2004 and 2016. We excluded other cancer before RCC diagnosis with minimum wash-out period of 2 years and no systemic therapy experience. The patients had treated with systemic therapy for metastatic RCC with or without cytoreductive nephrectomy (CN group and non-CN group). To reduce selection bias, propensity score matching (PSM) was conducted by age, sex and Charlson comorbidity index (CCI). Overall survival (OS) was compared between two groups by Kaplan-Meier method and Cox regression model in total cohort and PSM cohort. RESULTS: Among 8,962 patients with metastatic RCC, 2,695 patients underwent cytoreductive nephrectomy with systemic therapy and 6,267 patients received only systemic therapy. Non-CN group had older age (p<0.0001), more male gender (p=0.03), and higher CCI (p<0.0001), but after PSM the variables were well-matched (D<0.1). In total cohort, cytoreductive nephrectomy was a significant factor for OS (hazard ratio [HR] 0.621, 95% confidence interval [CI] 0.589-0.656, p<0.0001). In PSM cohort, cytoreductive nephrectomy was also a significant factor for OS (HR 0.807, 95% CI 0.742-0.878, p<0.0001). CONCLUSIONS: CN was performed in about 30% of metastatic RCC with systemic therapy. In appropriate surgical candidates, CN may offer a benefit for OS. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e255-e256 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joonhee Gook More articles by this author Jae Hun Shim More articles by this author Byung Hoon Chi More articles by this author Jin Wook Kim More articles by this author In Ho Chang More articles by this author Tae-Hyoung Kim More articles by this author Soon Chul Myung More articles by this author Se Young Choi More articles by this author Expand All Advertisement Loading ...

Role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).

4582 Background: The role of CN in mRCC was challenged by the results of the CARMENA trial in the targeted therapy (TT) era. We sought to evaluate the role of both upfront and deferred CN in pts receiving modern IO-based and TT regimens. Methods: Pts with synchronous mRCC who received systemic therapy (tx) for mRCC after 2011 were included from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic tx alone, systemic-&gt; CN, and CN-&gt; systemic tx. Overall survival (OS) was calculated from the time of initiation of first therapy – systemic or CN. Patient characteristics were compared using chi-squared tests or t-test. Weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regressions with time-varying covariates were used to assess the effect of tx on survival. Adjustment was conducted via inverse probability of treatment weighing based on the generalized propensity score, estimated via Bayesian Additive Regression Trees. Covariates in the model were age, gender, race, insurance at mRCC diagnosis, and IMDC risk group. Results: Of 1719 pts with mRCC, 972 (56.5%) received systemic tx alone, 605 (35.1%) received CN-&gt; systemic tx, and 142 (8.2%) received systemic-&gt;CN. 310 pts received IO or IO/IO, 123 pts received IO+TT and 1152 pts received only TT. The median follow-up was 37.1 months. In adjusted analyses using propensity score weighting and time-varying covariates, CN-&gt; systemic was significantly associated with improved OS compared with systemic tx alone (Table). When stratifying groups by type of systemic treatment (IO and TT), there was improvement of OS in the CN groups compared to systemic tx alone, although we lacked power to reach statistical significance. Among CN-treated patients, the order of systemic tx relative to CN did not change OS (hazard ratio [HR] = 1.00, 95% CI 0.76-1.32, p=0.96). Conclusions: Using a national, EHR-based cohort, which includes a large number of IO treated pts, our findings support an oncologic role for CN in select mRCC pts. The timing of CN, for pts who were able to receive both systemic therapy and CN, may not affect overall outcome. The associated improvement in survival of CN is seen in pts receiving IO and TKI based systemic tx.[Table: see text]

The comparison of cytoreductive nephrectomy (CN) with tyrosine kinase inhibitor therapy alone in patients with primary metastatic renal cell carcinoma (mRCC).

304 Background: We aimed to compare overall survival (OS) between patients with metastatic renal cell carcinoma (mRCC) treated by cytoreductive nephrectomy (CN) and those not treated by CN. Methods: We retrospectively evaluated 278 patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019. Patients were divided into two groups, CN group (immediate or deferred CN) and systemic TKI therapies alone without CN (Ctrl group). The OS was compared in all patients between the Ctrl and CN groups, between the Ctrl and immediate CN groups, between the Ctrl and deferred CN groups, and between the deferred CN and immediate CN groups. Analyses were weighted using the propensity score–based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances. Results: The median age of the patients was 65 (range 59–73) years. Of the 278 patients, 132 and 146 were in the Ctrl and CN (immediate: 107 and deferred: 39) groups, respectively. A significant difference was noted between the Ctrl and CN groups in age, clinical stage, IMDC risk factors, and the number of metastatic sites. An IPTW-adjusted Cox regression analysis revealed a significant difference in OS between the Ctrl and CN groups and between the Ctrl and immediate or deferred CN groups. However, there was no significant difference in OS between immediate and deferred CN groups. Conclusions: The OS in CN group was significantly longer than that in Ctrl group even after the adjustment of potential selection biases.

Long-term survival outcomes of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: A systematic review and individual patient data meta-analysis.

317 Background: The role of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy agents remains controversial. We used reconstructed individual patient data (IPD) to compare the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone for mRCC. Methods: We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: July 21, 2020). We reconstructed the Kaplan-Meier curves and subsequently recuperated IPD for overall (OS), progression-free (PFS) and cancer-specific survival (CSS) from individual studies. We performed one-stage random-effects frequentist and Bayesian meta-analyses of OS, PFS, and CSS using parametric and non-parametric estimates. We also performed a subgroup analysis focusing on upfront CN and excluding patients with deferred CN. The risk of bias was assessed using the ROBINS-I and RoB2 tools. Results: Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. No studies were found to be at critical risk of bias. A total of 3,990 patients were included, with 2,234 in the CN group and 1,756 in the non-CN group. Our frequentist meta-analysis showed superior OS (HR = 0.58, 95% CI: 0.54-0.62, p&lt;0.0001) and CSS (HR = 0.63, 95% CI: 0.53-0.75, p &lt; 0.0001) in favor of CN. No clinically meaningful differences were observed in the PFS between the two groups (HR = 0.90, 95% CI: 0.80-1.02, p=0.09). The OS benefit was also observed in the upfront CN subgroup (HR = 0.70, 95% CI 0.63-0.78, p&lt;0.001). Similar results were obtained with non-parametric frequentist and Bayesian approaches (Table). Conclusions: The combination of CN and targeted therapy for mRCC is associated with superior long-term survival outcomes compared with targeted therapy alone. Careful patient selection based on prognostic factors is required to achieve optimal outcomes. [Table: see text]

Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis.

Simple SummaryCytoreductive nephrectomy (CN) refers to the removal of the primary renal tumor in the setting of metastatic renal cell carcinoma. In the past, the combination of CN with cytokine-based immunotherapy was considered the standard of care. However, CN’s role during the targeted treatment era remains controversial. We attempted to address this issue by performing a systematic review and meta-analysis of the literature. We synthesized data from 15 studies comparing CN and targeted therapy to targeted therapy alone. Our results show that CN combined with targeted therapy was associated with increased survival compared to targeted therapy only. Careful patient selection is required to take full advantage of any survival benefit that CN may offer. Future research endeavors should focus on developing appropriate prognostic models to guide appropriate patient selection for CN.The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains controversial during the targeted therapy era. To reconcile the current literature, we analyzed the reported survival data at the individual patient level and compared the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone in patients with mRCC. We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: 21 July 2020). We recuperated individual patient data from the Kaplan–Meier curves for overall (OS), progression-free (PFS), and cancer-specific survival (CSS) from each study. We subsequently performed one-stage frequentist and Bayesian random-effects meta-analyses using both Cox proportional hazards and restricted mean survival time (RMST) models. Two-stage random-effects meta-analyses were also performed as sensitivity analyses. A subgroup analysis was also performed to determine the effect of CN timing. Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. In the one-stage frequentist meta-analysis, the CN group had superior OS (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.54–0.62, p < 0.0001) and CSS (HR: 0.63, 95% CI: 0.53–0.75, p < 0.0001). No meaningful clinical difference was observed in PFS (HR: 0.90, 95% CI: 0.80–1.02, p = 0.09). One-stage Bayesian meta-analysis also revealed superior OS (HR: 0.59, 95% credibility interval [CrI]: 0.55–0.63) and CSS (HR: 0.63, 95% CrI: 0.53–0.75) in the CN group, while no meaningful clinical difference was detected in PFS (HR: 0.91, 95% CrI: 0.80–1.02). Similar results were obtained with the RMST models. The OS benefit was also noted in the two-stage meta-analyses models, and in the subgroup of patients who received upfront CN. The combination of CN and targeted therapy for mRCC may lead to superior long-term survival outcomes compared to targeted therapy alone. Careful patient selection based on prognostic factors is required to optimize outcomes.