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.

Ex-Vivo Treatment of Tumor Tissue Slices as a Predictive Preclinical Method to Evaluate Targeted Therapies for Patients with Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.