Search Results (23)

Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. With the advent of immune checkpoint inhibitors (ICIs) and targeted therapies, the contemporary relevance of CRN coupled with first-line immunotherapy and targeted therapy combination regimens warrants re-evaluation. Methods: This retrospective cohort study utilized the TriNetX research network to identify patients aged 18–90 years diagnosed with mRCC between 2005 and 2024 who received first-line systemic therapies. Patients were stratified into two cohorts based on receipt of CRN status within one year of diagnosis. Propensity score matching (1:1) was done to adjust baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to compare five-year overall survival between the groups. Results: Among 5960 eligible patients, 1776 (888 CRN matched to 888 who did not) formed the cohort of analysis. The CRN group demonstrated significantly higher five-year survival (57.7% vs. 45.0%, p < 0.0001) with a hazard ratio of 1.56 (95% CI: 1.33–1.83). Subgroup analyses showed consistent survival benefits across all four NCCN-recommended first-line regimens—Axitinib + Pembrolizumab: 64.0% (CRN) vs. 53.3% (no CRN), p = 0.01; Cabozantinib + Nivolumab: 50.1% vs. 40.4%, p = 0.004; Lenvatinib + Pembrolizumab: 37.4% vs. 22.8%, p = 0.012; Nivolumab + Ipilimumab: 56.4% vs. 46.1%, p = 0.005. Conclusions: In the era of modern immunotherapy and targeted agents, CRN remains associated with improved survival in patients with mRCC receiving NCCN-recommended first-line regimens. These findings support the continued evaluation of CRN as a component of multimodal therapy, particularly in patients with favorable risk profiles. Full article

Objectives: The incidence of renal cell carcinoma (RCC) has been rising, largely due to increased incidental detection from widespread imaging. Although synchronous distant metastasis (SM) with a primary renal tumor measuring <4 cm (cT1a) is uncommon, its presence may influence survival outcomes and the utility of cytoreductive nephrectomy. We sought to investigate clinical characteristics, metastatic patterns, treatments, and survival outcomes of patients with T1a RCC. Methods: All patients aged ≥18 years diagnosed with RCC between 2004 and 2019 were extracted from the National Cancer Database. The Cochran–Armitage test was used for trend analysis, while multivariable analyses were conducted to identify variables associated with SM and to assess the impact of cytoreductive surgery on mortality across isolated metastatic sites. Kaplan–Meier analysis was performed to compare survival outcomes. Results: A total of 263,911 individuals diagnosed with T1a RCC were analyzed in the study. Among them, 114,661 patients (43.4%) were classified as having cT1a tumor stage, and of these patients with cT1a RCC, 2275 (2.0%) exhibited SM. The proportion of SM cT1a was 3.39% in 2004 and 2.08% in 2019, with an Average Annual Percent Change (AAPC) of −0.037% (p = 0.830). The most common sites of metastasis were bone (59%), followed by lung (35%), liver (16%), and brain (12%). Resection of the primary tumor and receipt of systemic therapy were significantly associated with reduced mortality among all metastatic sites, especially in individuals with lung-only metastases (HR = 0.02, p = 0.013). Metastasectomy was associated with improved survival in patients with brain-only metastases (HR = 0.26, p = 0.006) but did not demonstrate the same benefit in patients with bone-, lung- or liver-only metastases. The worst 5-year OS rate was observed in cases with metastasis to multiple sites, whereas isolated metastases had similar survival rates (p < 0.0001). Our findings are limited by retrospective study design. Conclusions: This comprehensive analysis of T1a RCC patients reveals that while synchronous metastasis is relatively uncommon (2.0%), it presents significant clinical challenges, with bone as the most common metastatic site, contrasting with the typical lung predominance in larger tumors. Primary tumor resection showed survival benefit in patients with isolated metastases, especially for lung-only metastasis. These findings highlight the heterogeneous nature of tumor biology in small renal masses and underscore the importance of tailored, multimodal treatment strategies for the effective management of SM T1a RCC. Full article

Background/Objectives: The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). Methods: We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022. Patients with the necessary laboratory studies available within 90 days before and by one year after surgery were included for study. PNS resolution was defined as an abnormal value compared to established laboratory cutoffs by one year after surgery. Multiple PNS in one patient was allowed, and resolution of each PNS was measured separately. OS and CSS were assessed using Kaplan–Meier curves and Cox proportional hazards models. Results: A total of 253 patients met inclusion criteria. A total of 177 patients (70.0%) met criteria for at least one PNS resolution by one year. Five-year OS and CSS rates were 15.7% and 36.2% for no PNS resolved, 24.5% and 31.6% for 1 PNS resolved, and 43.0% and 58.2% for ≥2 PNS resolved, respectively (p < 0.001). On multivariable analysis, no PNS resolution was associated with worse OS (HR 2.75, p < 0.001) and CSS (HR 2.62, p < 0.001) compared to ≥2 PNS resolved. Conclusions: Resolution of preoperative PNS abnormalities by one year following surgery is associated with improved OS and CSS in patients with mRCC. Full article

Objectives: 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. Methods: 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. Results obtained: 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). Conclusions: 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. Full article

Background: This study aimed to investigate the effect of cytoreductive nephrectomy (CN) on the survival outcomes of nivolumab used as a subsequent therapy after the failure of at least one anti-vascular endothelial growth factor (VEGF) agent in patients with metastatic clear-cell renal-cell carcinoma (ccRCC). Methods: We included 106 de novo metastatic ccRCC patients who received nivolumab after progression on at least one anti-VEGF agent. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. Results: Of the 106 de novo metastatic ccRCC patients, 83 (78.3%) underwent CN. There were no statistical differences between the two groups in terms of age, gender, Eastern Cooperative Oncology Group (ECOG) score, tumor size, International Metastatic RCC Database Consortium (IMDC) risk group, number of previous treatment lines, first-line anti-VEGF therapy, or metastasis sites (p = 0.137, p = 0.608, p = 0.100, p = 0.376, p = 0.185, p = 0.776, p = 0.350, and p = 0.608, respectively). The patients who received nivolumab with CN had a longer time to treatment discontinuation (TTD) [14.5 months, 95% confidence interval (CI): 8.6–20.3] than did those without CN 6.7 months (95% CI: 3.9–9.5) (p = 0.001). The median overall survival (OS) was 22.7 months (95% CI: 16.1–29.4). The patients with CN had a median OS of 22.9 months (95% CI: 16.3–29.4), while those without CN had a median OS of 8.1 months (95% CI: 5.6–10.5) (p = 0.104). In the multivariate analysis, CN [hazard ratio (HR): 0.521; 95% CI: 0.297–0.916; p = 0.024] and the IMDC risk score (p = 0.011) were statistically significant factors affecting TTD; however, the IMDC risk score (p = 0.006) was the only significant factor for overall survival. Conclusions: Our study showed that the TTD of nivolumab was longer in metastatic ccRCC patients who underwent cytoreductive nephrectomy. Full article

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. Full article

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. Full article

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy. In cases where systemic treatment is deemed appropriate, the absence of direct comparisons among the various combination therapies complicates the selection of a first-line approach. The clinician is faced with the challenge of making decisions based on patient-specific factors such as performance status, risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium, comorbidities, and disease characteristics, including the number and location of metastases and tumor histology. Considering these concerns, we propose, as a member of a Tuscany Interdisciplinary Uro-Oncologic Group, an algorithm to streamline the decision-making process for mRCC patients, offering guidance to clinicians in their day-to-day clinical practice. Full article

(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. Full article

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. Full article

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research. Full article

The treatment of metastatic renal cell carcinoma has undergone considerable advances in the last two decades. Cytoreductive nephrectomy and metastasectomy retains a role in patients with a limited metastatic burden. The choice of optimal treatment regimen remains a matter of debate. The article summarises the current role of surgery in metastatic kidney cancer. Full article

Treatment advances in kidney cancer continually evolve. The focus of treatment options continues with oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) or intravenous immune checkpoint inhibitors (ICIs). Multiple trials exploring the role of adjuvant treatment after cytoreductive nephrectomy in high-risk clear cell renal cell carcinoma are currently ongoing. The discovery of biomarkers may help determine which patients benefit from these treatments, but these are not yet available outside clinical studies. Trials with combination therapies are also ongoing, especially using novel therapies with new mechanisms of action, and will hopefully provide more clues on proper patient and therapy selection in the adjuvant setting. Full article

Renal cell carcinoma (RCC) has a natural tendency to invade the venous system with formation of a venous tumor thrombus in the renal vein, which can extend proximally into the inferior vena cava (IVC) and in some cases into the right atrium. The presence of venous involvement significantly worsens prognosis. Despite recent advances in systemic therapies, surgery remains the most effective method of treatment and in the case of complete removal of all tumor, it provides satisfactory long-term survival and must be attempted whenever possible. Several surgical techniques have been proposed, but all are associated with a high rate of perioperative complications and mortality. Minimally invasive approaches are mainly applicable for less extended IVC thrombi, while open surgery remains the gold standard for this category of patients. Most IVC thrombi can be managed without use of circulatory support by using different methods of IVC control depending on the thrombus level. However, use of cardiac bypass with or without deep hypothermic cardiac arrest is indicated in some patients with bulky intraatrial tumor thombi. In select patients presenting with IVC tumor thrombus and synchronous distant metastases, cytoreductive nephrectomy with IVC tumor thrombectomy may be considered with or without neoadjuvant systemic therapy. Surgery for RCC with venous thrombus is complex and requires experienced multidisciplinary surgical, anesthesia, and critical care teams at high-volume centers to achieve the best outcomes. Full article

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. Full article