Efficacy of combined organ-sparing management of invasive upper urinary tract urothelial carcinoma.

Introduction: The study aimed to evaluate the objective response level to neoadjuvant platinum-based chemotherapy and tumour complexity reduction in patients with invasive upper tract urothelial cancer (UTUC), and to estimate the functional and oncological outcomes of the combined organ-sparing approach compared to radical nephroureterectomy. Material and methods: This prospective, non-randomised cohort study was conducted by the National Cancer Institute of Ukraine. Patients with invasive UTUC were enrolled between October 2016 and January 2021. Patients were allocated to one of two cohorts depending on the estimated glomerular filtration rate (eGFR) of the affected kidney. In cases where eGFR was preserved, neoadjuvant chemotherapy with an organ-sparing approach was used; all other cases proceeded directly to radical nephroureterectomy. Results: A total of 64 patients (32 in each cohort) with invasive UTUC were enrolled. Both groups were comparable in terms of age, sex, T stage, maximal tumour size, eGFR, Eastern Cooperation Oncology Group (ECOG) performance status, body mass Index (BMI), and haemoglobin level. After four cycles of chemotherapy, there were no cases of progressive disease, stable disease [16 (50%), partial response; 12 (38%); and complete response, 4 (12%)]. The average maximal tumour size decreased by 2.3 cm. Prior to surgical treatment, total GFR according to scintigraphy did not statistically differ in both groups (р = 0.13). However, 3 months after surgery patients who underwent the organ-sparing approach had a better total eGFR (р = 0.0039), which was probably owing to the preserved kidney function (18.9 +5.1 mL/min). Better 2-year recurrence-free survival was also observed in the organ-sparing management group (85% vs 72%, log-rank test; p = 0.03). Conclusions: Neoadjuvant systemic therapy reduces the surgical complexity of invasive UTUC without influencing the safety profile. The gemcitabine/cisplatin regimen leads to high regression rates among invasive UTUC, which could result in an organ-sparing approach in selected cases. Kidney function preservation remains a key parameter that can increase the possibility of effective systemic treatment.