Project description:The role of CN in the treatment of metastatic renal cell carcinoma (mRCC) has been studied over the course of the past few decades. With the advent of immuno-oncologic (IO) agents, there has been a paradigm shift in the treatment of RCC. Within this new era of cancer care, the role of CN is unclear. There are several studies currently underway that aim to assess the role of CN in combination with these therapies. We reviewed articles examining CN, both historically and in the modern immunotherapy era. While immune-oncologic agents are relatively new and large clinical trials have yet to be completed, data thus far is promising that CN may provide clinical benefit. Multiple ongoing trials may clarify the role of CN in this new era of cancer care.
Project description:ObjectiveTo assess whether regional lymph node dissection could improve the prognosis of patients with metastatic renal cell carcinoma.MethodsWe reviewed data on 258 patients who underwent cytoreductive nephrectomy at Memorial Sloan Kettering Cancer Center, New York, USA, some of whom received a concurrent lymph node dissection. The primary outcome measure was overall survival. A Cox proportional hazards regression model included, age, pathological stage, lymphadenopathy, tumor size, modified Memorial Sloan Kettering Cancer Center criteria, site of metastatic disease and lymph node dissection. We created a logistic regression model to evaluate risk factors for node-positive disease. Survival analyses were carried out for lymph node template (hilar vs other) and number of nodes removed (0-3, 4-7 or ≥8).ResultsOf 258 patients, 177 (69%) underwent lymph node dissection, and positive nodes were found in 59 (33%). The 5-year overall survival was 21% for patients who underwent lymph node dissection and 31% for patients who did not. No significant difference in survival was found among patients receiving or not receiving lymph node dissection. The 5-year overall survival was 27% and 9% for negative and positive nodal status, respectively (P < 0.0005). For patients who underwent lymph node dissection, the presence of lymphadenopathy was a significant predictor of node-positive disease (odds ratio 25.0, 95% confidence interval 9.04-69.4, P < 0.0001).ConclusionsLymph node dissection carried out during cytoreductive nephrectomy is not associated with a survival benefit. Lymph node-positive disease represents a poor prognostic variable; therefore, lymph node dissection should be considered as a staging procedure for clinical trials.
Project description:Renal cell carcinoma (RCC) displays a wide spectrum of oncological prognosis and clinical behavior, and is noted for its generally poor outcome in metastatic settings. However, the introduction of immunotherapy after the cytokine era has changed the landscape of treatment for metastatic RCC, outperforming previous targeted therapy and providing new hope for patients with advanced disease. Cytoreductive nephrectomy (CN) has been the center of controversy, with questionable survival benefit when compared to systemic therapy. Despite discouraging results from the two randomized clinical trials (CARMENA & SURTIME), interest into the role of CN is being rekindled, and contemporary real-world studies provide supporting evidence to suggest that CN may still have a role in well-selected patients treated or expecting treatment with immunotherapy, not only for symptomatic control but also for oncological benefit. In this review article, we attempt to review the modern insight into the role of CN for metastatic RCC in contemporary medicine, with a focus on treatment with immune checkpoint inhibitor combination-based immunotherapy.
Project description:Historically, immediate cytoreductive nephrectomy (CN) was considered the standard of care in patients with metastatic renal cell carcinoma (mRCC) who were fit enough to undergo surgery. Recently, 2 randomized controlled trials, SURTIME and CARMENA, have questioned the role of immediate CN and initiated an ongoing debate on the proper indications and timing of CN. Although some patients still benefit from immediate CN, other patients require immediate systemic treatment, and some of them might benefit from deferred CN in the absence of disease progression. This study provides an overview of the history of CN, an in-depth analysis of SURTIME and CARMENA, and highlights the current indications for performing immediate or deferred CN.
Project description:PurposeCytoreductive nephrectomy (CN) benefits a subset of patients with metastatic renal cell carcinoma (mRCC), however proper patient selection remains complex and controversial. We aim to characterize urologists' reasons for not undertaking a CN at a quaternary cancer center.MethodsConsecutive patients with mRCC referred to MSKCC urologists for consideration of CN between 2009 and 2019 were included. Baseline clinicopathologic characteristics were used to compare patients selected or rejected for CN. The reasons cited for not operating and the alternative management strategies recommended were extrapolated. Using an iterative thematic analysis, a framework of reasons for rejecting CN was designed. Kaplan-Meier estimates tested for associations between the reasons for not undertaking a CN and overall survival (OS).ResultsOf 297 patients with biopsy-proven mRCC, 217 (73%) underwent CN and 80 (27%) did not. Median follow-up of patients alive at data cut-off was 27.3 months. Non-operative patients were older (p = 0.014), had more sites of metastases (p = 0.008), harbored non-clear cell histology (p = 0.014) and reduced performance status (p < 0.001). The framework comprised seven distinct themes for recommending non-operative management: two patient-fitness considerations and five oncological considerations. These considerations were associated with OS; four of the oncological factors conferred a median OS of less than 12 months (p < 0.001).ConclusionWe developed a framework of criteria by which patients were deemed unsuitable candidates for CN. These new insights provide a novel perspective on surgical selection, could potentially be applicable to other malignancies and possibly have prognostic implications.
Project description:Two randomized trials published in 2001 established CyNx for patients with metastatic renal carcinoma (mRCC) as a treatment standard in the cytokine era. However, first-line systemic therapy for mRCC changed in 2005 with FDA approval of VEGFR TKIs. We evaluated the patterns of use of CyNx from 2000 to 2008.The National Cancer Database was queried for patients diagnosed with mRCC. Patients who underwent CyNx were identified and were further categorized by pre-VEGFR versus VEGFR TKI era, race, insurance status, and hospital. For these subcategories, prevalence ratios (PRs) were generated using the proportion of patients with mRCC undergoing CyNx versus those not undergoing CyNx.Of the 47,417 patients (pts) identified with mRCC, the prevalence of cytoreductive nephrectomy increased 3% each year from 2000 to 2005 (P < .0001), then decreased 3% each year from 2005 to 2008 (P = .0048), with a significant difference between the eras (0.97 vs. 1.025; P < .0001). Black and Hispanic pts were less likely than Caucasian pts to undergo CyNx. Pts with Medicaid, Medicare, and no insurance were less likely than pts with private insurance to undergo CyNx. Pts diagnosed at community hospitals were significantly less likely than pts at teaching hospitals to undergo CyNx.The use of CyNx has declined in the VEGFR-TKI era. In addition, racial and socioeconomic disparities exist in the use of CyNx. The results of pending randomized trials evaluating the role of CyNx in the VEGFR-TKI era are awaited to optimize use of this modality and address potential disparities.
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.
Project description:IntroductionWe report the case of a 69 y.o. man with a left solitary kidney presenting 3 tumoral masses and suspicion of a left adrenal nodular tumor.Presentation of case48 months previously, the patient underwent laparoscopic right radical nephrectomy and adrenalectomy for a clear cell renal carcinoma, with a tumor free adrenal gland. 3D laparoscopic transperitoneal left cytoreductive nephrectomy and left adrenalectomy were performed within 23 min warm ischemia with no need of post operatory hemodialysis. The pathology exam reported metachronous metastases on left adrenal gland and on a left multifocal tumoral solitary kidney from the contralateral clear cell renal carcinoma prior diagnosed and treated at this patient.DiscussionCytoreductive nephrectomy on a solitary kidney brings technical challenges for the laparoscopic approach, especially when the tumor presents as multifocal lesions. Contralateral metachronous metastases and adrenal involvement in case of renal carcinoma are scarcely presented in the literature.ConclusionThe "en bloc" excision of the tumoral masses optimized warm ischemia time and improved the technical approach, even if the endophytic presentation imposed difficulty.
Project description:The Southwest Oncology Group (SWOG)1931 trial, also known as PROBE (ClinicalTrials.gov Identifier: NCT04510597) is a phase III study evaluating the role of cytoreductive nephrectomy (CN) in metastatic renal cell cancer (RCC). Kidney cancer presenting with synchronous metastases has demonstrated shorter survival outcome compared to the patients relapsing with metastases after nephrectomy. Previously, CN has been associated with survival improvement when interferon-based systemic therapy was used. In the setting of antivascular therapy sunitinib, a prospective randomized clinical trial demonstrated no benefit of CN. Immune checkpoint-based combination therapy has now become the standard-of-care in the frontline setting for RCC. The role of nephrectomy or primary resection has not been evaluated in the setting of immune checkpoint-based systemic therapy. The sequence and optimal timing of nephrectomy is also not established. The PROBE study design attempts to answer the question whether CN has an impact on overall survival outcomes in RCC within the context of immune checkpoint-based combination regimens. The study requires starting with systemic therapy; any one of the FDA approved immunotherapy-based regimens at the time the study was activated are permitted. The disease status and response are evaluated at 9-12 weeks of therapy and then consented patients are randomized 1:1 to receive CN or to continue systemic therapy. The patients who have rapid disease progression are considered ineligible for randomization as they need a switch in systemic therapy. Both groups should continue systemic therapy as long as they are tolerating the treatment and continuing to derive clinical benefit. Quality-of-life, tumor genomic testing, microbiome, radiomics and circulating tumor DNA assessments as predictive biomarkers are planned as study correlatives. The study hypothesis is that CN will improved OS in synchronous metastatic RCC when surgery is performed after starting systemic immune checkpoint-based combination therapy. A potential mechanism leading to improved survival is the broader antigen spread and higher neoantigen load enabled by the primary tumor enhancing the efficacy of the immune therapy. CN after initial systemic therapy would help select the patient subset most likely to benefit and will potentially enable eradication of immune resistant clones within the primary tumor.