Elevated preoperative neutrophil-tolymphocyte ratio may be associated with decreased overall survival in patients with metastatic clear cell renal cell carcinoma undergoing cytoreductive nephrectomy

Objective:Inflammatory serum markers have proven to be a powerful predictive tool of patient prognosis in cancer treatment for a wide variety of solid organ malignancies,predominantly in the context of localized disease.In this study we evaluated the preoperative neutrophil-to-lymphocyte ratio(NLR)as a predictive tool in patients with metastatic clear cell renal cell carcinoma(RCC).Methods:Sixty-four patients with metastatic clear cell RCC undergoing nephrectomy were selected.Only patients with preoperative NLR were included for survival analysis.Patients were categorized into high and low NLR score determined by plotting the NLR ROC curve.Multivariable analysis was performed.Results:Median age was 60.8 years(38.2-81.2).Median follow-up time was 8.1 months(0.1-106.3).Fuhrman grade distribution was:2(3.1%)grade 1,6(9.4%)grade 2,24(37.5%)grade 3 and 32(50.0%)grade 4.Median NLR score was 3.5(1.4-31.0).NLR
4 was associated with decreased overall survival compared toNLR<4(p=0.017).Multivariable survival analysis showed NLR
4 as an independent predictor of survival(Hazard ratio(HR)2.41,95%CI 1.05-5.50,p=0.03).Conclusion:Elevated preoperative NLR is associatedwith poor prognosis in patients withmetastatic kidney cancer.Preoperative NLR is a useful tool,which can predict prognosis,stratify patients for postoperative surveillance,and help guide decisions for therapy.

Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy

Background：The metastatic renal cell carcinoma （mRCC） patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival （OS） benefits.It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor （VEGFR-TKI） will benefit from such cytoreductive nephrectomy either.The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.Methods：Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital （Institute）,Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively.The survival analysis was performed by the Kaplan-Meier method.Comparisons between patient groups were performed by Chi-square test.A Cox regression model was adopted for analysis of multiple factors affecting survival,with a significance level of α =0.05.Results：Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy （cytoreductive nephrectomy group） and 23 patients were treated with targeted therapy alone （noncytoreductive nephrectomy group）.The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups,respectively （P =0.041）.Age ≤45 years （P =0.002）,a low or high body mass index （BMI 〈19 or 〉30 kg/m2） （P =0.008）,a serum lactate dehydrogenase （LDH） concentration 〉 1.5 × upper limit of normal （P =0.025）,a serum calcium concentration 〉1 0 mg/ml （P =0.034）,and 3 or more metastatic sites （P =0.023） were independent preoperative risk factors for survival.The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone （40.0 months vs.23.2 months,P =0.042）,while those with more than 2 risk factors did not.Conclusions：Five risk factors （age,BMI,LDH,serum calcium,and number of metastatic sites） seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.

Comparison of immediate vs. deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma

Cytoreductive nephrectomy has been a mainstay in treating patients with synchronous metastatic renal cell carcinoma(mRCC)for over two decades.It was supported in part by level 1 evidence that showed improved survival for patients undergoing radical nephrectomy before initiation of systemic therapy dating back almost 20 years.Since that time,the landscape of systemic therapy for mRCC has shifted mainly from IL-2 based therapy to tyrosine kinase inhibitors(TKIs)targeting the vascular endothelial growth factor pathway,and now to immunotherapy with PD-L1 inhibitors.Given the significant advancements in systemic therapy for patients with mRCC,the role of cytoreductive nephrectomy and sequencing of treatment has been questioned.Recent randomized studies appear to disprove the theory that upfront cytoreduction improves overall survival,particularly in the TKI era,and thus treating physicians are faced with conflicting data to guide treatment decisions.The role of cytoreductive nephrectomy is in evolution,and so is the timing of surgery in selected patients.Familiarity with available evidence coupled with patient selection and targeted therapy should help to inform decision-making.Currently,an initial course of systemic therapy followed by consideration of nephrectomy in those with a favorable response may be the most prudent algorithm outside the context of a clinical trial.

Renal cell carcinoma:An update for the practicing urologist

Systemic therapy for metastatic renal cell carcinoma(mRCC)has evolved drastically,with agents targeting vascular endothelial growth factor(VEGF)and the mammalian target of rapamycin(mTOR)now representing a standard of care.The present paper is to review the current status of relevant clinical trials that were either recently completed or ongoing.(1)Though observation remains a standard of care following resection of localized disease,multiple trials are underway to assess VEGF-and mTOR-directed therapies in this setting.(2)While the preponderance of retrospective data favors cytoreductive nephrectomy in the context of targeted agents,prospective data to support this approach is still forthcoming.(3)The first-line management of mRCC may change substantially with multiple studies exploring vaccines,immune checkpoint inhibitors,and novel targeted agents currently underway.In general,prospective studies that will report within the next several years will be critical in defining the role of adjuvant therapy and cytoreductive nephrectomy.Over the same span of time,the current treatment paradigm for first-line therapy may evolve.