Impact of Timing of Immunotherapy and Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Data on Survival Outcomes from the CKCis Database.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13-0.68) and CN-ST (HR 0.68, CI 0.47-0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26-0.77) and CN-ST (HR 0.9, CI 0.68-1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

Approaches to Treating High Risk and Advanced Renal Cell Carcinoma (RCC): Key Trial Data That Impacts Treatment Decisions in the Clinic.

The treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone. The role of adjuvant therapy in patients with high-risk disease who have undergone cytoreductive nephrectomy and potentially metastasectomy is also an area of continuing interest. While the S-TRAC study demonstrated a disease-free survival benefit for adjuvant sunitinib, no overall survival benefit was shown, and multiple other studies of adjuvant VEGFR TKI therapy have been negative. Subsequently, adjuvant pembrolizumab has shown a benefit in overall survival, whereas trials of neoadjuvant and adjuvant nivolumab, adjuvant atezolizumab, and adjuvant ipilimumab plus nivolumab have all been negative. Finally, the role for cytoreductive nephrectomy continues to be an area of active debate. The CARMENA study raised important questions about the role of cytoreductive nephrectomy given the advances in VEGFR TKI therapy but was characterized by accrual difficulties and a significant number of patients not receiving treatment according to the study protocol. Two ongoing studies (NORDIC-SUN and PROBE) seek to further address the role of cytoreductive nephrectomy in the doublet therapy era.

Impact of Cytoreductive Nephrectomy in the Management of Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study.

In this study, we aimed to determine the utility of cytoreductive nephrectomy (CN) in real-world clinical practice and investigate whether CN contributes to improved oncological outcomes in patients with metastatic renal cell carcinoma (mRCC). This retrospective multicenter cohort study enrolled patients with mRCC who received systemic therapy at six institutions between May 2005 and May 2023. The patients were divided into those who did not undergo CN (Group I) and those who underwent CN (Group II). The primary endpoints were oncological outcomes, including cancer-specific survival (CSS) and progression-free survival (PFS). Altogether, 137 patients with mRCC were included in this study. The median CSS was 14 months in Group I and 32 months in Group II (p < 0.001). Additionally, the median PFS in Groups I and II was 5 and 13 months, respectively (p = 0.006). A multivariate analysis showed that CN was an independent prognostic factor for CSS and PFS. Hence, CN is a potential treatment modality that can improve oncological outcomes in patients with mRCC.

Active Surveillance in Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with a variable clinical course. While therapies for treatment of this condition have progressed, they are not without toxicity. In some patients, active surveillance (AS) of this disease is increasingly considered to delay its toxicity. This article seeks to review the literature and discuss management of metastatic renal cell carcinoma, specifically regarding upfront AS, the role of radiation therapy in delaying systemic therapy, and surveillance after initial treatment with systemic therapy. Median time on AS prior to initiation of systemic therapy ranged from 14 to 60 months across studies. AS is appropriate to offer in favorable or intermediate risk, asymptomatic, and systemic treatment naïve patients with mRCC.

Cytoreductive Nephrectomy in Select Primary Metastatic Renal Cell Carcinoma Patients: A Comprehensive Nationwide Outcome Analysis.

(1) Background: The role of cytoreductive nephrectomy (CN) is controversial in patients with primary metastatic renal cell carcinoma (mRCC). (2) Methods: We evaluated the impact of CN, or no CN, followed by first-line targeted therapy (TT) in a nationwide unselected cohort of 437 consecutive patients with primary mRCC over a two-year period with a minimum of five years of follow-up. Data sources were national registries supplemented with manually extracted information from individual patient medical records. Cox proportional hazards estimated the hazard ratio (HR) of overall death and cancer-specific death after one and three years. (3) Results: 210 patients underwent CN and 227 did not. A total of 176 patients (40%) had CN followed by TT, 160 (37%) had TT alone, 34 (8%) underwent CN followed by observation, and 67 (15%) received no treatment. After adjustments in Model 2, patients treated with TT alone demonstrated a worsened overall survival (OS) compared to those treated with CN + TT, HR 0.63 (95% CI: 0.19-2.04). (4) Conclusions: In this nationwide study, CN was associated with enhanced outcomes in carefully selected patients with primary mRCC. Further randomized trials are warranted.

Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial.

BACKGROUND: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment. METHODS/DESIGN: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis. DISCUSSION: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03977571 June 6, 2019.

The Effect of Treatment Intensification on Other-Cause Mortality in Clear-Cell Metastatic Renal Cell Carcinoma Patients.

BACKGROUND: The effect of treatment intensification (systemic therapy [ST] + cytoreductive nephrectomy (CN) vs. ST alone) is unknown regarding rates of other-cause mortality (OCM) in clear-cell metastatic renal cell carcinoma (ccmRCC). We hypothesized that intensified treatment (ST + CN) may result in higher OCM, than when ST is used alone. METHODS: Within the Surveillance, Epidemiology, and End Results database, all ccmRCC patients treated 2010-2018 either with ST + CN or ST alone were identified. Propensity score matching (PSM), cumulative incidence plots, multivariable competing risks regression analyses and 6 months' landmark analyses addressed OCM and cancer-specific mortality (CSM) according to treatment status. RESULTS: Of 2271 ccmRCC patients, 1233 (54%) were treated with ST + CN vs 1038 (46%) with ST alone. After 1:1 PSM, OCM was 5.3 vs. 4.6 % (P = .5) and CSM was 73.4 vs. 88.4% (P < .001) in ST + CN vs. ST alone patients. In multivariable competing risks regression, the combination of ST and CN was not associated with higher OCM (HR 1.3; 95% CI 0.8-2.1; P = .4), vs. ST alone. However, the combination of ST and CN was independently associated with lower CSM (HR 0.5; 95% CI 0.5-0.6; P < .001), vs. ST alone. After 6 months' landmark analyses, these multivariable associations remained unchanged. CONCLUSIONS: The current study indicates no OCM-disadvantage in ST + CN ccmRCC patients, relative to their ST alone counterparts. Conversely, a strong association with lower CSM was recorded in ST + CN patients, relative to their ST alone counterparts. These associations are robust and remained unchanged after strictest statistical adjustment including control for immortal time bias.

The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features.

BACKGROUND: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden. OBJECTIVE: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery. DESIGN, SETTINGS, AND PARTICIPANTS: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness. RESULTS AND LIMITATIONS: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%. CONCLUSIONS: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection. PATIENT SUMMARY: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians.

Surgical treatment decision and clinical value of molecularly defined renal carcinoma with highly aggressive behavior / 现代泌尿外科杂志

Molecularly defined renal carcinoma is a pathologic subtype of renal cell cancer (RCC) with a definite driver gene, which was first proposed in the 2022 WHO classification of tumors of the urinary system and male reproductive organs. The fumarate hydratase-deficient renal cell carcinoma and SMARCB1-deficient renal medullary carcinoma are highly aggressive and lethal subtypes. Due to the low incidence and lack of research on the mechanism, there is almost no effective treatment for these aggressive RCC subtypes. Cytoreductive nephrectomy or metastasectomy are important methods to improve the survival and quality of life of metastatic RCC patients under effective systemic therapy. However, for the highly aggressive RCC, the clinical value of the above surgical strategies is still unclear. In this review, we will discuss these problems in order to provide reference for the improvement of prognosis for patients with highly aggressive RCC subtypes.

Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma.

PURPOSE: The use of systemic immune checkpoint blockade before surgery is increasing in patients with metastatic renal cell carcinoma, however, the safety and feasibility of performing consolidative cytoreductive nephrectomy after the administration of systemic therapy are not well described. PATIENTS AND METHODS: A retrospective review of patients undergoing nephrectomy was performed using our prospectively maintained institutional database. Patients who received preoperative systemic immunotherapy were identified, and the risk of postoperative complications were compared to those who underwent surgery without upfront systemic treatment. Perioperative characteristics and surgical complications within 90 days following surgery were recorded. RESULTS: Overall, we identified 220 patients who underwent cytoreductive nephrectomy from April 2015 to December 2022, of which 46 patients (21%) received systemic therapy before undergoing surgery. Unadjusted rates of surgical complications included 20% (n = 35) in patients who did not receive upfront systemic therapy and 20% (n = 9) in those who received upfront systemic immunotherapy. In our propensity score analysis, there was no statistically significant association between receipt of upfront immunotherapy and 90-day surgical complications [odds ratio (OR): 1.82, 95% confidence interval (CI): 0.59-5.14; P = 0.3]. This model, however, demonstrated an association between receipt of upfront immunotherapy and an increased odds of requiring a blood transfusion [OR: 4.53, 95% CI: 1.83-11.7; P = 0.001]. CONCLUSION: In our cohort, there was no significant difference in surgical complications among patients who received systemic therapy before surgery compared to those who did not receive upfront systemic therapy. Cytoreductive nephrectomy is safe and with low rates of complications following the use of systemic therapy.

Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib.

Introduction: The effectiveness of nivolumab plus cabozantinib for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus remains unclear. Case presentation: A 77-year-old male was diagnosed with right papillary renal cell carcinoma with a metastatic lesion on Gerota's fascia, lymph node metastasis, and inferior vena cava tumor thrombus. He was treated with nivolumab plus cabozantinib. As all lesions regressed enough to permit complete resection, radical nephrectomy, thrombectomy, and retroperitoneal lymph node dissection were performed. No viable malignant cells were identified histopathologically. Despite the discontinuation of nivolumab plus cabozantinib, there has been no recurrence for 9 months. Conclusion: Nivolumab plus cabozantinib has effectiveness for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus.

Blepharoptosis revealing a metastatic renal cell carcinoma: A rare case report.

INTRODUCTION: Renal cell carcinoma (RCC) is a relatively rare malignancy often discovered incidentally. Approximately 15 % of cases are metastatic at diagnosis, commonly affecting the lungs, bones, lymph nodes, and liver. We present an exceptional case of RCC metastasizing to the eyelid. CASE PRESENTATION: A 67-year-old female with no prior cancer history exhibited rapidly progressing left blepharoptosis. Examination revealed a painless, solid eyelid mass. Immunohistochemistry of the eyelid mass biopsy identified a carcinoma potentially of renal origin. A thorax, abdomen, and pelvis CT scan confirmed the presence of a right renal mass. Following a multidisciplinary discussion, we decided to proceed with an upfront cytoreductive nephrectomy and surgical excision of the eyelid metastasis. DISCUSSION: Eyelid metastasis revealing a renal cell carcinoma is exceedingly rare. Immunohistochemistry plays a pivotal role in detecting primary renal tumors. Prognostic models, particularly the IMDC, guide therapeutic decisions. In the era of immune checkpoint inhibitors, cytoreductive nephrectomy remains a safe option for well-selected patients with favorable risk mRCC. CONCLUSION: Recognizing unusual metastatic sites of RCC is vital due to its asymptomatic nature and the potential impact of delayed diagnosis on prognosis. Immunohistochemistry plays a critical role in diagnosis. Multidisciplinary tumor board discussions are essential for tailored management of favorable risk mRCC patients.

The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.

Renal cell carcinoma not otherwise specified: A case report in Indonesia.

Renal cell carcinoma not otherwise specified (RCC NOS) is a very rare type of kidney cancer which used for renal tumors that do not fit into any of the well-recognized subtypes. We reported a case of RCC NOS of a 64-year-old male presenting an enlarging left flank mass. Abdominal CT showed a left kidney mass infiltrating to the adrenal, with pulmonary metastases. Cytoreductive nephrectomy and lymphadenectomy were performed and diagnosis of RCC NOS was confirmed through histopatological and immunohistochemistry examination.

Role of Surgery in Metastatic Renal Cell Carcinoma.

Surgery has historically been the mainstay of treatment for metastatic renal cell carcinoma (mRCC), but recent clinical trials demonstrated that contemporary systemic therapies alone are non-inferior to cytoreductive nephrectomy (CN). Thus, the current role of surgery is not precisely defined. CN remains an appropriate upfront treatment for the palliation of severe symptoms, select cases of metastatic non-clear cell renal cell carcinoma, for consolidation following systemic therapy, and in the setting of oligometastatic disease. Metastasectomy is ideally utilized to achieve a disease-free state when there is minimal morbidity associated with surgery. Given the heterogenous nature of mRCC, the decision for systemic therapy and surgery should be made through a multidisciplinary approach tailored to each individual patient.

Long-term outcomes after cytoreductive nephrectomy and thrombectomy of patients with metastatic renal cell carcinoma with venous tumor thrombus: a retrospective study from a large Chinese center.

BACKGROUND: Targeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients. PATIENTS AND METHODS: A total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan-Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS. RESULTS: The median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS. CONCLUSION: Cytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.