A new scaffold-free tumoroid model provides a robust preclinical tool to investigate invasion and drug response in Renal Cell Carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent kidney cancers, which is often asymptomatic and thus discovered at a metastatic state (mRCC). mRCC are highly heterogeneous tumors composed of subclonal populations that lead to poor treatment response rate. Several recent works explored the potential of ccRCC tumoroids culture derived from patients. However, these models were produced following a scaffold-based method using collagen I or Matrigel that exhibit lot variability and whose complexity could induce treatment response modifications and phenotypic alterations. Following the observation that ccRCC tumoroids can create their own niche by secreting extracellular matrix components, we developed the first scaffold-free tumoroid model of ccRCC tumors. Tumoroids from mice as well as from human tumors were generated with high success rate (≥90%) using a magnetic suspension method and standard culture media. Immunofluorescence analysis revealed their self-organization capacities to maintain multiple tumor-resident cell types, including endothelial progenitor cells. Transcriptomic analysis showed the reproducibility of the method highlighting that the majority of gene expression patterns was conserved in tumoroids compared to their matching tumor tissue. Moreover, this model enables to evaluate drug effects and invasiveness of renal cancer cells in a 3D context, providing a robust preclinical tool for drug screening and biomarker assessment in line with alternative ex vivo methods like tumor tissue slice culture or in vivo xenograft models.

Superselective Ischemia in Robotic Partial Nephrectomy Does Not Provide Better Long-term Renal Function than Renal Artery Clamping in a Randomized Controlled Trial (EMERALD): Should We Take the Risk?

BACKGROUND: Superselective clamping of tumor-targeted arteries aims to eliminate ischemia of the remnant kidney while keeping tumor bed bloodless during excision. OBJECTIVE: To evaluate the impact of superselective clamping on long-term renal function, compared with renal artery early unclamping. DESIGN, SETTING, AND PARTICIPANTS: A randomized monocentric single-blind trial (1:1) was conducted from February 2018 to August 2019. Patients with a single renal tumor were candidates for a robot-assisted partial nephrectomy (RAPN) in a referral center. EMERALD (NCT03679572) was powered to include 50 patients with an interim analysis after 30 cases. INTERVENTION: Superselective RAPN (SS-RAPN) with near-infrared fluorescence (NIRF) or conventional RAPN with renal artery early unclamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the percent change of estimated glomerular filtration rate (eGFR) in the operated kidney after 6 mo (combination of eGFR and relative function on 99mTc-DMSA scintigraphy). Secondary endpoints assessed feasibility and safety of the technique. RESULTS AND LIMITATIONS: Relative eGFR reduction in the operated kidney at 6 mo did not differ significantly (-21.4% vs -23.4%, p=0.66). This absence of difference remained after adjusting on percentage of kidney volume preserved, which was an independent predictor of functional preservation. There were no significant differences in terms of blood loss, change in hemoglobin, postoperative complications, transfusion, and conversion to radical nephrectomy (two vs zero) or to open surgery (one vs zero). Despite a good accrual, the steering committee interrupted the trial after the interim analysis for futility given the absence of trend in favor of SS-RAPN. CONCLUSIONS: SS-RAPN using NIRF does not provide better renal function preservation than renal artery clamping, questioning the interest of this technique at a higher risk of bleeding. PATIENT SUMMARY: In this randomized controlled trial, superselective clamping of tumor feeding arteries did not show any advantage in terms of long-term renal function compared with conventional artery clamping.