Current role of cytoreductive nephrectomy in metastatic renal cell carcinoma
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ABSTRACT:
SUBMITTER: Van Praet C
PROVIDER: S-EPMC8057358 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The management of metastatic renal cell carcinoma (mRCC) continues to be a therapeutic challenge; however, the options for systemic therapy in this setting have exploded over the past 20 years. From the advent of toxic cytokine therapy to the subsequent discovery of targeted therapy (TT) and immune checkpoint inhibitors, the landscape of viable treatment options continues to progress. With the arrival of cytokine therapy, two randomized trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) plus interferon therapy and this approach became the standard for surgical candidates. However, it was difficult to establish the role and the timing of CN with the subsequent advent of TT, just a few years later. More recently, two randomized phase III studies completed in the TT era questioned the use of CN and brought to light the role of risk stratification while selecting patients for CN. Careful identification of the mRCC patients who are likely to have a rapid progression of the disease is essential, as these patients need prompt systemic therapy. With the continued advancement of systemic therapy using the immune checkpoint inhibitors as a first line therapy, the role of CN will continue to evolve.
| S-EPMC8033221 | biostudies-literature
Project description:PURPOSE OF REVIEW:Recent publications evaluating cytoreductive nephrectomy in the era of targeted therapy emphasize the importance of patient selection. We reviewed the predictive role of genetic alterations in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy. RECENT FINDINGS:Studies evaluating the association between genetic alterations and outcomes following systemic treatment for mRCC include mainly patients after cytoreductive nephrectomy. Expression of proangiogenic genes, single nucleotide polymorphisms involving genes of the vascular-endothelial growth factor (VEGF) pathway and somatic mutations of chromatin remodeling genes were associated with response to VEGF-targeted therapy. Outcomes following treatment with mammalian target of rapamycin (mTOR) inhibitors were initially associated with mTOR/TSC1/TSC2 mutations; however, subsequent studies did not validate these findings but rather found an association between loss of PTEN expression and PBRM1 mutations and improved outcomes. Loss of PBRM1 was initially linked to response to immunotherapy; however, larger studies question this association and showed high expression of T-effector gene signature predicted improved outcome. Primary tumors with low intratumor heterogeneity but elevated somatic copy-number alterations were associated with rapid progression at multiple sites. SUMMARY:Genetic alterations may help select patients for cytoreductive nephrectomy and optimize timing of treatment. Intratumor heterogeneity and genetic discordance between primary and metastatic tumors may limit clinical applicability. Future studies should evaluate approaches to overcome these limitations.
| S-EPMC7029802 | biostudies-literature
Project description:PurposeThe role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies.Materials and methodsWe included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival.ResultsOf 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99).ConclusionsOur findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.
| S-EPMC9187610 | biostudies-literature
Project description:Cytoreductive nephrectomy has been an integral part of management in metastatic renal cell carcinoma for patients with good performance status, based on the benefit shown by prospective trials in the interferon era and retrospective trials in the targeted therapies era. Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), the first prospective phase III trial comparing a targeted agent alone (sunitinib) versus nephrectomy plus sunitinib, has been recently published, showing non-inferiority for the nephrectomy-sparing arm. In this article, we discuss the impact of nephrectomy including its immune-mediated effects, surgical morbidity and mortality, and the clinical data supporting the indications of nephrectomy in order to analyze the CARMENA trial in context, with the aim to identify optimal strategies for different patient populations in the metastatic setting.
| S-EPMC6403966 | biostudies-literature
Project description:We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden. The post-operative course was uneventful and the patient was discharged home on postoperative day one. Temsirolimus was resumed one week after surgery and the patient reported returning to his normal activities at the two week follow-up visit. We highlight important clinical features of metastatic renal cell carcinoma, the surgical considerations for cytoreductive nephrectomy and the detailed multidisciplinary care the patient received throughout this case report.
| S-EPMC5385451 | biostudies-other
Project description: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.
| S-EPMC10143323 | biostudies-literature
Project description:The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48-0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48-0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18-0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20-0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61-2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN.
| S-EPMC5633591 | biostudies-literature
Project description:(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.
| S-EPMC10968994 | biostudies-literature
Project description:In the early 2000s, cytoreductive nephrectomy in addition to systemic cytokines became standard of care for treating metastatic renal cell carcinoma. Since that time, the development of novel systemic targeted therapies and immuno-oncologic agents have challenged the utility of cytoreductive nephrectomy in clinical practice. In 2019, the controversial CARMENA study was published, providing the first level one evidence suggesting that cytoreductive nephrectomy combined with targeted therapy yielded no survival advantage over targeted therapy alone in intermediate and poor risk metastatic renal cell carcinoma patients. Later that year, the SURTIME trial demonstrated that patients undergoing targeted therapy with delayed nephrectomy maintained a survival advantage over those that underwent upfront cytoreductive nephrectomy followed by targeted therapy. Both of these studies underscored the importance of patient selection and timing of cytoreductive nephrectomy and systemic therapy. As new immuno-oncologic agents are trialed, particularly in combination, the role of cytoreductive nephrectomy will continue to be questioned. In this narrative review, we discuss the evolution of the role of cytoreductive nephrectomy in treating metastatic renal cell carcinoma through the context of the ever-changing landscape of targeted therapies and immuno-oncologic agents. We assess the evidence for cytoreductive nephrectomy with respect to patient factors, timing of surgery, and combination with other therapies.
| S-EPMC7751973 | biostudies-literature
Project description:ObjectiveTo assess which patients respond best following cytoreductive nephrectomy for renal cell carcinoma (RCC) with sarcomatoid dedifferentiation (sRCC) and whether outcomes are improving over time.MethodsWe identified 562 patients with metastatic RCC treated between 1989 and 2018 with cytoreductive nephrectomy. We reviewed baseline clinical and pathologic characteristics, including the presence of sRCC, and metastatic sites at time of nephrectomy. The primary study endpoint was overall survival (OS). Univariate and multivariate Cox-regression analyses were used to identify significant predictors of OS.ResultsThe study cohort had 192 sRCC patients, with a median age of 59 years. Frequently involved metastatic locations were lung (n = 115), retroperitoneal nodes (n = 63), and axial skeleton (n = 43). Lung metastasis were more prevalent in clear cell histology (P = .0017) whereas nodal involvement was associated with nonclear cell subtypes (P = .0064). Median follow-up was 14 months. Estimated 2- and 5-year OS were 34.1% and 14.8%, respectively. On multivariate analysis, metastases to the liver (HR = 1.64; 95% CI 1.02-2.63; P = .04), lung (HR = 1.50; 95% CI 1.05-2.14; P = .03), retroperitoneal nodes (HR = 1.52; 95% CI 1.03-2.25; P = 0.04) and nonclear cell histology (HR = 1.61; 95% CI 1.10-2.35; P = .01) were associated with worse OS in the sRCC cohort.ConclusionOS after cytoreductive nephrectomy for sRCC and non-sRCC is improving over time. In patients with sRCC, presentations with unifocal metastasis not involving the liver or lung, clear cell histology and node negative disease have better outcomes following cytoreductive nephrectomy and may yield greater benefit from the procedure.
| S-EPMC7082891 | biostudies-literature