Cytoreductive Nephrectomy In Patients Research Articles

Utilization of Partial Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma.

Cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) is a standard of care. Partial nephrectomy (PN) in the setting of metastatic disease is an uncommon occurrence, and we aimed to characterize its utilization in a modern cohort. The National Cancer Database was reviewed for patients with mRCC from 2010 to 2017. Patients with cTanyNanyM1 who underwent cytoreductive surgery in the form of PN or radical nephrectomy (RN) were compiled. Our primary outcome was survival outcome for patients who underwent PN compared to RN. Secondary outcomes included 30-day readmission, length of stay, and survival outcomes. A total of 13,896 patients with mRCC who underwent cytoreductive surgery were identified. In total, 13,242 underwent RN and 654 underwent PN. The RN population was more likely to have cN positive disease, while the PN population was more likely to have cT1 disease. Length of stay, readmission and 30-day mortality were not significantly different between PN and RN, but overall mortality and 90-day mortality favored PN (p < 0.001). Cox regression for death showed PN with improved overall survival (HR 0.782, p < 0.001). Logistic regression for predictors of cytoreductive PN revealed cT1 and cN0 as significant factors. Overall survival, as seen on KM analysis, identified that PN exhibited improved 2-year (67.1% vs. 52.0%) and 5-year (40.7% vs. 29.2%) overall survival relative to RN (p < 0.001). PN is an infrequent treatment with mRCC and its utilization is stable from 2010 to 2017. Overall survival is significantly better for those undergoing PN, likely due to their favorable oncologic disease characteristics.

Abstract 7523: An integrated analysis of radiologic and pathological responses in patients with metastatic renal cell carcinoma who presented with primary renal tumor in situ and received first-line nivolumab plus ipilimumab followed by cytoreductive nephrectomy

Abstract Background: The decision to perform cytoreductive nephrectomy (CN) and timing of CN in patients (pts) with metastatic renal cell carcinoma (mRCC) and primary who respond to immune checkpoint therapy (ICT) is a matter of debate. In CheckMate-214, nivolumab plus ipilimumab (N+I) yielded a 35% objective response rate in the primary; however, there is a paucity of pathological data from nephrectomy specimens (Nx) after treatment with N+I. We sought to investigate the radiologic and pathological responses and correlate the findings with outcomes in pts receiving 1L N+I followed by CN. Methods: We reviewed the medical records and Nx of pts with mRCC who received N+I followed by CN at our institution (2016-2021). H&amp;E slides were reviewed to determine the % of residual viable malignant cells. Pathological response was defined as tumor viability ≤20%, and pathological complete response (pCR) defined as absence of residual cancer. Radiologic response was defined as ≥30% reduction in primary size. Progression-free survival (PFS) and overall survival (OS) were determined from date of CN. Results: 22 pts (median age 59) are included: 18 (81.8%) males, 19 (86%) Caucasian, 20 (91%) had clear-cell histology, 20 (91%) had ECOG Performance Status 0-1, 10 (45%) had intermediate-risk disease and 12 (55%) had poor-risk disease by IMDC. Median ICT duration before CN was 6.5 months (mo) (range, 2-19 mo). 17 (77%) completed 4 cycles of N+I, and 16 (73%) received N maintenance before CN. 5 pts (23%) had grade 3/4 immune-related adverse effects; 1 pt did not complete 4 cycles of N+I due to hepatitis. There were no therapy-related deaths. 12 pts (54.5%) had progressive disease (PD); 3 pts (14%) died of RCC. Median PFS was 22 mo, median OS not reached (NR). Pts with pathological response had greater radiologic reduction in primary size compared to pts without pathological response (median reduction 38% vs. 15% p-value 0.01), smaller final primary pathological size (median 5.7 cm vs. 10.65 cm p-value 0.002), and lower pathological yT stage (pT0: 1, pT1: 6, pT2: 2 pT3: 3, pT4: 0 vs. pT0: 0, pT1: 1, pT2: 0, pT3: 8, pT4: 1 p-value 0.045); ICT duration was similar between groups (median 5.5 mo vs. 7 mo p-value 0.733). 6 pts achieved low viability within 5 mo of ICT. In 9 pts with optimal radiopathological response [viability ≤20% and ≥30% primary size reduction], PFS was longer compared to PFS in pts with suboptimal radiopathological response: median PFS NR vs. 17 months (HR 0.23, 95% CI 0.076 - 0.741; p-value 0.041). In 13 pts with suboptimal response, 10 (77%) had PD, the most common sites of PD were lymph nodes [6 pts (60%)] and brain [3 pts (30%)]. Conclusions: In this small cohort, N+I yielded a low pCR in Nx of pts with mRCC. Radiologic response but not ICT duration was associated with low tumor viability. Citation Format: Leticia Campos Clemente, Omar Alhalabi, Matthew T. Campbell, Guillermo Corredor Alonso, Kieko Hara, Pavlos Msaouel, Andrew C. Johns, Chad Tang, Jose A. Karam, Priya Rao, Nizar M. Tannir. An integrated analysis of radiologic and pathological responses in patients with metastatic renal cell carcinoma who presented with primary renal tumor in situ and received first-line nivolumab plus ipilimumab followed by cytoreductive nephrectomy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7523.

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

BackgroundPrimary 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/designTo 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.DiscussionThe 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 registrationClinicalTrials.gov NCT03977571 June 6, 2019.

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immunotherapy: A systematic review and meta-analysis.

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immunotherapy: A systematic review and meta-analysis.

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

PurposeThe 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 MethodsA 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. ResultsOverall, 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]. ConclusionIn 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.

Comparison of upfront versus deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving systemic therapy: A systematic review and meta-analysis.

This study aimed to conduct a pooled analysis to compare the outcomes of patients with metastatic renal cell carcinoma (mRCC) who received presurgical systemic therapy (ST; including immunotherapy and/or targeted therapy) followed by cytoreductive nephrectomy (deferred CN; dCN) with those who underwent upfront CN (uCN) followed by ST. The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was conducted in PubMed, Embase, Web of Science, Scopus, and Cochrane Library database to identify eligible comparative studies up to April 2023. To evaluate their relevance, pooled hazard ratio (HR) with 95% confidence intervals (CIs) were calculated. A total of 3157 patients were included in nine studies. The dCN group was observed to be correlated with superior overall survival (OS) compared to the uCN group (HR=0.71, 95% CI 0.57-0.89, P=0.003). Moreover, we conducted subgroup analyses according to the type of ST, sample size, gender, age, and risk score, and observed similar outcomes for OS across most subgroups. The results of this study demonstrated that dCN may be associated with improved OS compared to uCN in patients with mRCC receiving ST. However, no significant differences were found between uCN and dCN groups in the immunotherapy-based combinations subgroup. Further research is needed to confirm these results.

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy.

Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

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 Association Between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm

BackgroundIt is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm. ObjectiveTo test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2006–2018), all mRCC patients with primary tumor size ≤4 cm were identified. Outcome measurements and statistical analysisPropensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non–clear-cell (non-ccmRCC) mRCC histology, historical (2006–2012) versus contemporary (2013–2018), and young (≤65 yr) versus old (>65 yr) patients. Results and limitationsOf 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001). ConclusionsThe current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age. Patient summaryIn the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics.

Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy

BackgroundRenal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT. ObjectiveHere, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status. Design, setting, and participantsA retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. InterventionCN performed at any time point; nephrectomy with curative intent was excluded. Outcome measurements and statistical analysisICT treatment duration (TD) and overall survival (OS) from ICT initiation were recorded. To address the immortal time bias, a time-dependent Cox regression model was generated that accounted for confounders identified by a directed acyclic graph as well as a time-dependent nephrectomy variable. Results and limitationsA total of 118 patients underwent CN, and of them, 89 underwent upfront CN. The results did not contradict the supposition that CN does not improve ICT TD (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.65–1.47, p = 0.94) or OS from ICT initiation (HR 0.79, 95% CI 0.47–1.33, p = 0.37). In patients who underwent upfront CN compared with those who did not undergo CN, there was no association with ICT duration or OS (HR 0.61, 95% CI 0.35–1.06, p = 0.08). A detailed clinical summary of 49 patients with mRCC and rhabdoid dedifferentiation is provided. ConclusionsIn this multi-institutional cohort of mRCC with S/R dedifferentiation treated with ICT, CN was not significantly associated with improved TD or superior OS when accounting for the lead time bias. There appears to be a subset of patients who derive meaningful benefit from CN, so improved tools for stratification prior to CN are needed to optimize outcomes. Patient summaryImmunotherapy has improved outcomes for patients with metastatic renal cell carcinoma (mRCC) who have sarcomatoid and/or rhabdoid (S/R) dedifferentiation, which is an aggressive and uncommon feature; yet, the utility of a nephrectomy in this setting is unclear. We found that nephrectomy did not significantly improve survival or time on immunotherapy for these patients with mRCC and S/R dedifferentiation; yet, there may be a subset of patients who benefit from this surgical approach.

Clinical and immunogenomic outcomes of consolidative cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immune checkpoint blockade.

720 Background: Immune checkpoint blockade (ICB) alone and in combination has dramatically improved outcomes in metastatic renal cell carcinoma (RCC). We performed in-depth clinical, histopathologic and immunogenomic analysis of a cohort of RCC patients treated with upfront ICB followed by delayed consolidative cytoreductive nephrectomy. This highly selected cohort included extreme responders defined by complete pathologic response and no evidence of disease at more than 25 months of follow-up. Methods: Clinicopathologic data was collected from 32 patients who received ICB (alone or combined with anti-VEGF therapy) and then subsequently underwent resection of primary tumor. Immunogenomic analysis was performed on select pre-treatment and nephrectomy tissue using targeted next-generation sequencing (MSK-IMPACT) and immunohistochemical (IHC) staining analyses. We further performed single-cell (sc)RNA sequencing of both peripheral blood and residual tumor tissue (where available), including 4 patients who demonstrated complete pathologic response. The Kaplan-Meier method was used to calculate survival outcomes. Results: All 32 patients underwent successful consolidative surgery and were further stratified based on evidence of radiographic progression, with 13 pts (40.6%) demonstrating no evidence of disease after surgery. The most common histopathology was clear cell RCC (n=29, 90.6%). Half the patients received dual ICB (CTLA-4/PD-1) (n=16, 50%), while the rest received an immunotherapy agent plus an anti-VEGF agent (n=13, 40.6%) or a single immunotherapy agent (n=3, 9.4%). Median follow-up for the cohort was 33.1 mo. (95%CI: 20.5-42.5) and median OS was 45.2 mo. (95%CI:23.9 – NR). Median OS for those who had progressive disease after CN was 25.5 (95%CI: 16.4- NR). At a median follow-up of 25.5 mo. in patients without evidence of disease after CN, 24-month survival rate was 100%. On pathologic evaluation, those without evidence of disease had a median of 8% (IQR: 0-35%) residual viable tumor. Mutational analysis revealed enrichment for BAP1 (n=3, 20.0% vs. n=0, 0%) and SETD2 (n=7, 46.7% vs. n=0, 0%) in progressive patients. scRNAseq and scTCRseq analysis of peripheral blood revealed distinct expansion of Natural Killer (NK), CD4 subsets and unique T cell clonal expansions amongst long term responders. Additionally, we identified an inverse relationship between NK cell populations and B cell infiltration in long term responders. Conclusions: Delayed cytoreductive nephrectomy in select patients is associated with favorable outcomes, especially in those who demonstrate complete response after surgery. Examination of this population offers opportunities for identification of unique tissue and peripheral based biomarkers for long term clinical responses in metastatic RCC.

The role of cytoreductive nephrectomy in the treatment of patients with metastatic kidney cancer - review article.

The role of cytoreductive nephrectomy (CN), i.e. the removal of a kidney involved by cancer in patients with advanced kidney cancer with distant metastases, is the subject of intense debate among urologists and oncologists. For many years, CN has been considered the gold standard in the treatment of patients at this stage of the disease, especially in patients in good general health with no significant contraindications to surgical treatment. The starting point for questioning the validity of CN was the publication of the results of the cancer du rein metastatique nephrectomie et antiangiogéniques and SURTIME clinical trials (2018 and 2019, respectively), which questioned the validity of surgery in some patients with late-stage cancer. Given the complexity of the disease, the role of removing the involved kidney is the subject of much controversy. In recent years, several studies have been conducted to evaluate the efficacy and safety of nephrectomy in patients with metastatic kidney cancer, resulting in conflicting information regarding the eligibility criteria for patients in different risk groups. The aim of this article is to analyse the available data, provide an up-to-date review of the literature, and discuss the controversies and challenges related to CN in patients with metastatic kidney cancer. The present literature review aims to organize and systematize the current state of knowledge, which may help in making clinical decisions regarding qualification for CN in patients with advanced kidney cancer.

Role of cytoreductive surgery in the era of immunotherapy.

The benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was first called into question in the tyrosine kinase inhibitors (TKIs) era. It remains undefined in the context of the recent development and approval of immune checkpoint inhibitors (ICIs) and level one evidence supporting the rapid adoption of dual ICI and combination ICI + TKI therapeutic approaches for mRCC. Our objective is to synthesize the available contemporary data regarding the safety, feasibility, and oncologic outcomes with CN for mRCC in the age of immunotherapy as well as to highlight trials in progress that will address this key knowledge gap. Data from the SURTIME and CARMENA trials provided insight to guide patient selection for CN in patients with mRCC receiving TKI-based treatment strategies. At present, there is a body of retrospective data supporting the safety and oncologic efficacy of CN in carefully selected patients with mRCC in both the upfront and delayed setting. The results of ongoing trials evaluating the safety and feasibility for CN as well as optimal patient selection and sequencing strategies are eagerly awaited. Although the optimal selection criteria and timing for CN remains to be established for patients with mRCC in the immunotherapy era, the available body of evidence underscores the importance of careful patient selection. Ongoing prospective studies, such as Cyto-KIK , PROBE , and NORDIC-SUN , will better define the role of CN in the rapidly evolving treatment landscape for mRCC.

2021 Consensus Statements on the Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma From the Korean Renal Cancer Study Group (KRoCS)

Purpose: The Korean Renal Cancer Study Group (KRoCS) provides consensus recommendations on the role of cytoreductive nephrectomy (CRN) in patients with metastatic renal cell carcinoma (mRCC).Materials and Methods: A group of mRCC experts from the Korean Urological Oncology Society convened at the 2021 KRoCS meeting on CRN for mRCC.Results: The consensus document was developed to address 4 questions related that were judged to be the most relevant to patient care: (1) Is there a role for CRN in patients planning targeted therapy? (2) Is there a role for CRN in patients planning immuno-oncology agents? (3) When is the optimal time of CRN in patients planning systemic treatment? (4) What is the ideal patient selection for CRN? The panelists have come up with following consensus. For mRCC patients, CRN should be considered only in those with IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) favorable and intermediate risk disease, regardless of the systemic treatment plans. Timing of CRN should consider the risk group as well as the number of risk factors, but is generally recommended for after assessing the degree of response to initial systemic treatment. Patients with good performance status, limited metastatic burden on top of resectable primary tumor are candidates recommended for CRN with or without metastasectomy with priority.Conclusions: In conclusion, there is still a role for CRN in the multimodality treatment of mRCC. Careful patient selection is of paramount importance. As the treatment landscape of mRCC continues to change, the role of CRN in the current immuno-oncology era will require more exploration.

The Role of Cytoreductive Nephrectomy in Renal Cell Carcinoma with Sarcomatoid Histology: A Case Series and Review of the Literature

Background: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. Patient and Methods: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. Results: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. Conclusion: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared. During a median follow-up period of 12.0months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P=0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P=0.0613). The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.

Survival Outcomes Associated With Cytoreductive Nephrectomy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

Level I evidence has failed to demonstrate an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC) in the modern era, which is at odds with observational studies reporting a marked OS benefit associated with these operations. These observational studies were not designed to adjust for unmeasured confounding. To assess whether cytoreductive nephrectomy is associated with improved OS in patients with metastatic ccRCC. This cohort study identified patients with metastatic ccRCC in the National Cancer Database from January 1, 2006, to December 31, 2016, who received systemic targeted therapy. The analysis was finalized on July 23, 2021. Receipt of cytoreductive nephrectomy. The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. Distance from the patients' zip code of residence to the treating facility was identified as a valid instrument and was used in a 2-stage residual inclusion instrumental variable analysis. Conventional adjustments for selection bias, multivariable Cox proportional hazards regression, and propensity score matching were performed for comparison. Measured covariates adjusted for in all analyses included age, sex, race, Charlson-Deyo score, facility type, year of diagnosis, clinical T stage, and clinical N stage. The final study population included 12 766 patients (median age, 63 years; IQR, 56-70 years; 8744 [68%] male; 11 206 [88%] White). Cytoreductive nephrectomy was performed in 5005 patients (39%). Conventional adjustments for selection bias demonstrated a significant OS benefit associated with cytoreductive nephrectomy (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% CI, 0.47-0.51; propensity score matching: HR, 0.48; 95% CI, 0.46-0.50). Instrumental variable estimates did not demonstrate an association between cytoreductive nephrectomy and OS (HR, 0.92; 95% CI, 0.78-1.09). Instrumental variable analysis did not demonstrate a survival advantage associated with cytoreductive nephrectomy for patients with metastatic ccRCC. This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets.

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 ...

Outcomes following cytoreductive nephrectomy without immediate postoperative systemic therapy for patients with synchronous metastatic renal cell carcinoma.

While the recent CARMENA trial evaluated upfront cytoreductive nephrectomy (CN) among patients treated with immediate subsequent systemic therapy for metastatic renal cell carcinoma (mRCC), the role of CN in patients not immediately requiring systemic therapy remains to be determined. To describe the oncologic outcomes of patients with de-novo synchronous mRCC who underwent CN +/- metastasis-directed therapy (MDT) and subsequent surveillance without planned immediate post-CN systemic therapy. Adults who underwent CN for unilateral, sporadic mRCC between 1996 and 2016 without immediate postoperative systemic therapy were identified using the prospectively-maintained Mayo Clinic Nephrectomy Registry. Co-primary outcomes were survival free of systemic therapy or death and overall-survival. Of 156 patients who met inclusion criteria for study, 37 (24%) patients were managed after CN with surveillance alone and 119 (76%) underwent MDT. Seventy-two patients ultimately initiated systemic therapy at a median of 0.7 years (IQR 0.3-1.7). Median follow-up among survivors was 6.2 years (IQR 4.4-9.5), during which time 133 patients died. At 1, 3, and 5 years, survival free of systemic therapy or death rates were 47%, 21% and 14% and overall-survival rates were 69%, 37%, and 28%. Among carefully selected patients managed with surveillance after CN +/- MDT, approximately half may avoid systemic therapy for 1 year, with a subset achieving long-term survival free of systemic therapy or death. Having a single metastatic site and disease amenable to complete metastasectomy are features of patients who might be well served with upfront CN +/- MDT.

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.