Outcomes of Cytoreductive Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Real World Data from Canadian Centers.

Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. The Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. Patients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. A total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52-0.82) and CN after ST (HR 0.41, 95% CI 0.28-0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. We evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. Two of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.

Dragomir A ，Nazha S ，Tanguay S ，Breau RH ，Bhindi B ，Rendon RA ，Kapoor A ，Hotte SJ ，Basappa N ，Fairey A ，So AI ，Kollmannsberger C ，Finelli A ，Hansen A ，Canil C ，Heng D ，Lattouf JB ，Bjarnason G ，Power N ，Pouliot F ，Wood LA ... -  《European Urology Focus》

Impact of Timing of Immunotherapy and Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Data on Survival Outcomes from the CKCis Database.

Park CL ，Moria FA ，Ghosh S ，Wood L ，Bjarnason GA ，Bhindi B ，Heng DYC ，Castonguay V ，Pouliot F ，Kollmannsberger CK ，Bosse D ，Basappa NS ，Finelli A ，Fallah-Rad N ，Breau RH ，Lalani AA ，Tanguay S ，Graham J ，Saleh RR ... -  《-》

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 ... -  《-》

Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

The role of cytoreductive nephrectomy (CN) has not yet been well characterized in the era of combination immunotherapy. To evaluate characteristics and outcomes for patients with metastatic renal cell carcinoma (mRCC) who received immuno-oncology (IO)-based combination therapy according to CN status. Using the International mRCC Database Consortium (IMDC), patients with mRCC who received frontline IO-based combinations were included. Upfront CN was defined as CN up to 3 mo before diagnosis of metastatic disease but before systemic therapy initiation. Deferred CN was defined as CN after systemic therapy initiation. Overall survival (OS) from initiation of systemic therapy was estimated via Cox proportional-hazards regression. A 12-mo landmark time and a time-varying covariate for CN status were used to mitigate potential bias. Of the 385 patients eligible for landmark analysis, 24, 182, and 179 underwent deferred CN, upfront CN, and no CN, respectively. Patients in the no CN subgroup were older (63 yr vs 57 yr in the deferred CN subgroup and 60 yr in the upfront CN subgroup; p = 0.001) and a higher proportion had bone metastases (44% vs 26% in the deferred CN subgroup and 23% in the upfront CN subgroup; p < 0.001). A lower proportion of patients in the upfront CN subgroup had IMDC poor risk (23% vs 43% in the no CN subgroup and 47% in the deferred CN subgroup; p < 0.001). On multivariable analysis, CN receipt was an independent favorable prognostic factor (hazard ratio 0.45, 95% confidence interval 0.26-0.78; p = 0.005). The study is limited by the lack of randomization and its retrospective nature. Despite changes in practice patterns with the advent of novel therapeutic agents, CN may still serve as an effective surgical intervention in carefully selected patients. For patients with metastatic kidney cancer, surgery to remove the primary tumor was traditionally the treatment of choice, but immunotherapy drugs are now another option for these patients. We analyzed data for contemporary patients with metastatic kidney cancer who received combination immunotherapy as their first treatment. We found that in selected patients receiving immunotherapy, surgery to remove the primary tumor as well can result in better prognosis.

Takemura K ，Ernst MS ，Navani V ，Wells JC ，Bakouny Z ，Donskov F ，Basappa NS ，Wood LA ，Meza L ，Pal SK ，Szabados B ，Powles T ，Beuselinck B ，McKay RR ，Lee JL ，Ernst DS ，Kapoor A ，Yuasa T ，Choueiri TK ，Heng DYC ... -  《European Urology Oncology》