Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor–targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data

Bruijn, Roderick de; Wimalasingham, Akhila; Szabados, Bernadett; Stewart, Grant D.; Welsh, Sarah J.; Kuusk, Teele; Blank, Christian U.; Haanen, John B.A.G.; Klatte, Tobias; Staehler, Michael; Powles, Thomas; Bex, Axel

doi:10.1016/j.euo.2019.12.004

Cited by 30 publications

(31 citation statements)

References 18 publications

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“…investigated 144 IMDC intermediate‐risk patients with deferred CN from pooled data of prospective phase 2 trials and compared them with a 131 IMDC intermediate‐risk dataset of immediate CN in the TT era. The IPTW‐adjusted OS in the deferred CN group was longer than in the immediate CN group (median OS 33.0 months vs 22.8 months; HR 0.72; 95% CI 0.52–0.996) 49 . We retrospectively compared IPTW‐adjusted OS between immediate CN and deferred CN in 100 REMARCC low score patients and 46 REMARCC high score patients, respectively, in the TT era.…”

Section: Deferred Cnmentioning

confidence: 99%

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

2022

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Abbreviations & Acronyms AS = active surveillance cCa = corrected calcium CI = confidence interval CN = cytoreductive nephrectomy CNS = central nervous system CR = complete response HR = hazard ratio ICI = immune checkpoint inhibitor IFN-a = interferon alpha IMDC = International Metastatic RCC Database Consortium IPTW = propensity scorebased inverse probability of treatment weight KPS = Karnofsky performance status mRCC = metastatic renal cell carcinoma NLR = neutrophil-tolymphocyte ratio ORR = objective response rate OS = overall survival PFS = progression-free survival RCC = renal cell carcinoma RCT = randomized controlled trial REMARCC = registry for metastatic renal cell carcinoma SBRT = stereotactic radiation therapy SRS = stereotactic radiosurgery TT = targeted therapy WBRT = whole-brain radiotherapy

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Section: Deferred Cnmentioning

confidence: 99%

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

2022

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“…Moreover, a considerable number of patients included in the sunitinibonly arm of the CARMENA trial (40/226, 17.7%) underwent secondary CN [6]. Current European Association of Urology guidelines recommend deferred CN as consolidative therapy in IMDC intermediate/poor-risk patients with sustained response on systemic therapy and good performance status [8,10]. The role of CN is even more controversial since the advent of immunotherapy, which has become the new backbone of systemic treatment in metastatic RCC (mRCC) patients.…”

Section: Introductionmentioning

confidence: 99%

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

Roussel

Campi

Larcher

et al. 2020

European Urology Oncology

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Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations: Intraoperative complications were observed in 69 patients (10.9%

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“…The SURTIME trial comparing upfront and deferred CN hinted that the latter may lead to an OS advantage but failed to provide a definitive answer, presumably due to poor accrual [71]. A study pooling data from multiple trials found an OS advantage of deferred over the upfront approach [72]. A more recent multi-institutional study using real-world data also came to the same conclusion [73].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis

Esagian¹,

Ziogas²,

Kosmidis

et al. 2021

Cancers

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The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains controversial during the targeted therapy era. To reconcile the current literature, we analyzed the reported survival data at the individual patient level and compared the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone in patients with mRCC. We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: 21 July 2020). We recuperated individual patient data from the Kaplan–Meier curves for overall (OS), progression-free (PFS), and cancer-specific survival (CSS) from each study. We subsequently performed one-stage frequentist and Bayesian random-effects meta-analyses using both Cox proportional hazards and restricted mean survival time (RMST) models. Two-stage random-effects meta-analyses were also performed as sensitivity analyses. A subgroup analysis was also performed to determine the effect of CN timing. Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. In the one-stage frequentist meta-analysis, the CN group had superior OS (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.54–0.62, p < 0.0001) and CSS (HR: 0.63, 95% CI: 0.53–0.75, p < 0.0001). No meaningful clinical difference was observed in PFS (HR: 0.90, 95% CI: 0.80–1.02, p = 0.09). One-stage Bayesian meta-analysis also revealed superior OS (HR: 0.59, 95% credibility interval [CrI]: 0.55–0.63) and CSS (HR: 0.63, 95% CrI: 0.53–0.75) in the CN group, while no meaningful clinical difference was detected in PFS (HR: 0.91, 95% CrI: 0.80–1.02). Similar results were obtained with the RMST models. The OS benefit was also noted in the two-stage meta-analyses models, and in the subgroup of patients who received upfront CN. The combination of CN and targeted therapy for mRCC may lead to superior long-term survival outcomes compared to targeted therapy alone. Careful patient selection based on prognostic factors is required to optimize outcomes.

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Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor–targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data

Cited by 30 publications

References 18 publications

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

Surgical and focal treatment for metastatic renal cell carcinoma: A literature review

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis

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