Cytoreductive Nephrectomy in the Era of Tyrosine Kinase and Immuno-Oncology Checkpoint Inhibitors.

The role for cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has evolved with advancements in systemic therapy. During the cytokine-based immunotherapy era, CN provided a clear survival benefit and was considered standard of care in management of mRCC. The development of targeted systemic therapy directed at the vascular endothelial growth factor pathway altered the treatment paradigm and accentuated the importance of risk stratification in treatment selection. This article reviews the literature evaluating the benefit of CN during the evolution of systemic therapy and provides clinical recommendations for current utilization of CN in patients with mRCC.

Biles MJ ，Patel HD ，Allaf ME 《-》

Is cytoreductive nephrectomy relevant in the immunotherapy era?

Singla N ，Ghandour RA ，Margulis V 《-》

Position of cytoreductive nephrectomy in the setting of metastatic renal cell carcinoma patients: does the CARMENA trial lead to a paradigm shift?

Introduction > The role of cytoreductive nephrectomy (CN) in combination with targeted therapy has been debated after the results of the CARMENA trial. We decided to reassess the available evidence on the setting of CN in metastatic renal cell carcinoma (mRCC) patients. Methods > Critical review of the literature focusing on CN in mRCC patients. Results > Previous trials demonstrated a survival benefit of CN during the cytokine-era. In the targeted therapies-era, retrospective studies has confirmed the survival benefit of CN but presented inherent selection biases. Recently, the CARMENA trial showed that sunitinib alone was not inferior to CN plus sunitinib, and could be followed by subsequent CN in good-responders patients. CN is found to be a morbid surgery (perioperative mortality rate of 0-13% and major postoperative complications rate of 3-36%) and should be avoided in patients with primary refractory disease, using targeted therapy as a selection tool. Some parameters have been associated with shorter overall survival, leading to propose up-front CN only to patients with good performance status, a high-volume renal tumor and a low metastatic burden. Conclusions > While previous studies demonstrated a survival benefit of CN, the CARMENA trial showed that immediate CN was not necessary in some patients with mRCC, leading to a paradigm shift. Targeted therapy should be proposed as first line treatment, and the response to pre-surgical therapy could be used as a selection tool for subsequent decision of CN in good-responders patients.

Dariane C ，Timsit MO ，Méjean A 《-》

Systematic Review of the Role of Cytoreductive Nephrectomy in the Targeted Therapy Era and Beyond: An Individualized Approach to Metastatic Renal Cell Carcinoma.

The role of cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) in the targeted therapy (TT) era is controversial. To assess if CN versus no CN is associated with improved overall survival (OS) in patients with mRCC treated in the TT era and beyond, characterize the morbidity of CN, identify prognostic and predictive factors, and evaluate outcomes following treatment sequencing. Medline, EMBASE, and Cochrane databases were searched from inception to June 4, 2018 for English-language clinical trials, cohort studies, and case-control studies evaluating patients with mRCC who underwent and those who did not undergo CN. The primary outcome was OS. Risk of bias was evaluated using the Cochrane Collaborative tools. We identified 63 reports on 56 studies. Risk of bias was considered moderate or serious for 50 studies. CN was associated with improved OS among patients with mRCC in 10 nonrandomized studies, while one randomized trial (CARMENA) found that OS with sunitinib alone was noninferior to that with CN followed by sunitinib. The risk of perioperative mortality and Clavien ≥3 complications ranged from 0% to 10.4% and from 3% to 29.4%, respectively, with no meaningful differences between upfront CN or CN after presurgical systemic therapy (ST). Notably, 12.9-30.4% of patients did not receive ST after CN. Factors most consistently prognostic of decreased OS were progression on presurgical ST, high C-reactive protein, high neutrophil-lymphocyte ratio, poor International Metastatic renal cell carcinoma Database Consortium (IMDC)/Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, sarcomatoid dedifferentiation, and poor performance status. At the same time, good performance status and good/intermediate IMDC/MSKCC risk classification were most consistently predictive of OS benefit with CN. In a randomized trial investigating the sequence of CN and ST (SURTIME), an OS trend was observed with CN after a period of ST in patients without progression compared with upfront CN. However, the study was underpowered and results are exploratory. Currently, ST should be prioritized in the management of patients with de novo mRCC who require medical therapy. CN maintains a role in patients with limited metastatic burden amenable to surveillance or metastasectomy, and may potentially be considered in patients with favorable response after initial ST or for symptom's palliation. In the contemporary era, receiving systemic therapy is the priority in metastatic kidney cancer. Nephrectomy still has a role in patients with limited burden of metastases, well-selected patients based on established prognostic and predictive factors, and patients with a favorable response after initial systemic therapy.

Bhindi B ，Abel EJ ，Albiges L ，Bensalah K ，Boorjian SA ，Daneshmand S ，Karam JA ，Mason RJ ，Powles T ，Bex A ... -  《-》

Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy. To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies. Retrospective data from patients with synchronous mRCC (n=1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not. OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria. Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p<0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52-0.69; p<0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively. CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials. We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.

Heng DY ，Wells JC ，Rini BI ，Beuselinck B ，Lee JL ，Knox JJ ，Bjarnason GA ，Pal SK ，Kollmannsberger CK ，Yuasa T ，Srinivas S ，Donskov F ，Bamias A ，Wood LA ，Ernst DS ，Agarwal N ，Vaishampayan UN ，Rha SY ，Kim JJ ，Choueiri TK ... -  《-》