This study aimed to evaluate the efficacy of neo-adjuvant targeted therapy (TT) in patients with localised clear-cell renal cell carcinoma (RCC). A special randomised trial was planned and conducted by the Research Department of Plastic and Reconstructive Oncology in the National Cancer Institute of Ukraine for testing the clinical efficacy of neo-adjuvant TT in the treatment of clear-cell localised RCC, and the primary endpoint was tumour response evaluation after TT. The secondary endpoints included evaluation of dependence between the use of neo-adjuvant TT and the probability of partial nephrectomy and the correlation between tumour size, stage, remaining functioning parenchyma volume, and response to systemic therapy. Overall, 118 patients met the inclusion criteria and were randomly assigned to receive combined treatment or surgery alone. The percentage of tumour regression ranged from 0% to 60%, and the median was (95% confidence interval) 20.5 ± 14.3 (16.8–24.3%). Most of the patients had a slightly positive response to TT (3%–29% decrease in tumour size); n = 44 (76.9%) cases. Partial response by the Response Evaluation Criteria in Solid Tumours, version 1.1, was observed in 14 (24.1%) patients and reached a maximum of 60% regression. Tumour reduction in the neoadjuvant TT group allowed kidney preservation in 53 (91.4%) patients. In the control group, the number of organ-sparing procedures was significantly lower (n = 20, 33.3%). The statistical difference was relevant (x² = 42.1). The positive results of neo-adjuvant TT obtained in our study indicate the clinical validity of combined treatment in patients with localised RCC.

A special randomised trial was planned and conducted by the Research Department of Plastic and Reconstructive Oncology at the National Cancer Institute of Ukraine, testing the clinical efficacy of neo-adjuvant TT in the treatment of clear-cell localised RCC. The eligibility of participating surgeons included sufficient surgical experience of >100 partial/radical nephrectomies per surgeon annually. The study was approved by the Institutional Review Board and local ethics committee, which was conducted as per with the Declaration of Helsinki and the Good Clinical Practice guidelines. The inclusion criteria were clinically and histologically confirmed localised clear-cell RCC (ccRCC) (T1-T2 N0 M0) with intermediate indications for both radical and partial nephrectomy: Lesion larger than 20 mm located in the renal hilum. Peripheral or polar RCC extending to kidney sinus. Remaining functioning parenchyma volume (RFPV) over 55%

Patients with chronic kidney disease, expected estimated glomerular filtration rate (eGFR) > 30 mL/min after surgery, coexisting malignant disease, and a history of any other systemic therapy were excluded. It was mandatory to exclude tumour extension and metastatic disease before patient enrolment. A special informed consent form was obtained from the study team and signed along with the National Health Care system form during the investigation. Tumour biopsy to confirm ccRCC was performed routinely, not less than 2 weeks before randomisation.

The results of a randomised prospective study evaluating the efficacy of neoadjuvant TT in the treatment of patients with localised RCC showed promising results.

Data from clinical trials indicate a connection between chronic kidney disease and cardiovascular risks. Conservative treatment allows preservation of additional functioning nephrons with reference rates of oncologic survival compared to nephrectomy. Currently, indications for conservative surgical treatment beyond the standard T1a stage are expanding. Particular attention is given to bilateral kidney lesions, single kidney tumours, and RCC with simultaneous opposite kidney pathology, which significantly diminishes its function, while nephrectomy may result in dialysis for such patients. This could induce a problem due to the insufficient number of dialysis beds and their high costs. In these cases, TT aims to reduce the RCC size and increase the likelihood of partial nephrectomy. This appears to be quite attractive from the perspective of RFPV preservation 

Neo-adjuvant TT in patients with surgically complex localised RCC resulted in clinical tumour regression, which provided a higher rate of conservative surgical treatment compared to similar patients without TT.

The positive results of neo-adjuvant TT obtained in our study indicate the clinical validity of further investigating preoperative systemic therapy in localised ccRCC.

Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics.

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Regards
Maya Wilson
Editorial Assistant
Journal of Nephrology and Urology