No-touch Radical Nephrectomy Technique Reduces Circulating Tumor Cell Release in Renal Cell Carcinoma Patients - a Randomized Controlled Trial

This study will study CTC profile in RCC, and their release into the blood circulation during LRN.

Included patients will be referred to the Renal Cancer Unit of the North Lisbon University Hospital Center (CHLUN) Urology Department with the diagnosis of a renal mass eligible for a LRN. Patients will have their diagnosis confirmed, be appropriately staged, and their management options will be decided after a shared and informed decision process in light of the current European Association of Urology (EAU) Guidelines on RCC. Patients < 18 years old and pregnant women will be excluded. Patients will be adequately informed of the study protocol, and will sign a specific informed consent.

Patients undergoing LRN will enter a two-arm prospective single-center randomized controlled trial, comparing a no-touch technique, with direct pedicle ligation (Group A) vs. the conventional dissection, and ligation of the renal pedicle with kidney traction (Group B). A peripheral blood sample will be collected at arrival to the operating room. After that, Group A patients will undergo a no-touch RN, with the dissection being done through the Gerota's fascia plane until exposure of the corresponding great vessel (vena cava on the right side, and aorta on the left side) is obtained. The renal pedicle will be directly isolated, and ligated using Weck® clips with no kidney manipulation. Group B patients will undergo a more conventional approach, starting with opening of the Gerota's fascia, identification of the ureter, traction on the peri-renal fat below the ureter while dissecting cephalad until the renal pedicle is reached. The renal pedicle will then be isolated while maintaining traction on the kidney, and peri-renal fat, and ligated using Weck® clips. A second peripheral blood sample will be collected at the time of specimen extraction. A third and fourth peripheral blood samples will be collected at post-operative days 1 and 30, respectively, to study CTC post-op kinetics. All samples will collect 7.5 mL of peripheral blood.

Patients presenting with hypofunctioning kidneys with indication for total nephrectomy will be used as controls. Total nephrectomy patients will undergo the randomization protocol, in a control arm.

The CTCs will be isolated from peripheral blood samples using a microfluidics size-based CTC capture device - Ruby™. Whole blood samples will be injected into the devices at an 80 µL/min flow rate. The CTCs captured on the devices will then be stained with antibodies to 4',6-diamidino-2-phenylindole (DAPI) to identify cell nuclei, cluster of differentiation antigen 45 (CD45) to identify leukocytes, cytokeratin 8/18 to identify epithelial CTCs, and vimentin to identify mesenchymal CTCs or CTCs which have undergone epithelial-to-mesenchymal transition. Blood samples will be processed no more than 30 minutes after collection.