Multimodal kidney-preserving approach in localised and locally advanced high-risk upper tract urothelial carcinoma.

Objectives: Multimodal kidney-preserving (MKP) strategies may be an option for patients with localised or locally advanced high-risk upper tract urothelial carcinoma (UTUC) who have a relative contraindication for nephroureterectomy (NU).

Materials and Methods: We studied patients with UTUC who were managed with MKP strategies, consisting of systemic anticancer therapy, with or without local/topical strategies after endoscopic control of intraluminal tumours. Primary end points were overall survival (OS) and progression-free survival (PFS).

Results: Fourteen patients received MKP treatment between August 2013 and April 2020. Median baseline estimated glomerular filtration rate was 43 mL/min/1.73m 2 . MKP was mainly pursued to avoid dialysis (10/14, 71%), followed by low performance status and/or comorbidities (2/14, 14%). All patients had received systemic therapy: chemotherapy (64%) and immunotherapy (36%). Endoscopic control and/or laser ablation was feasible in 7 (50%) patients. Calculated overall risk of non-organ confined disease was 35%. Predicted 2-year and 5-year relapse-free probability (RFP) was 74% (24-92%) and 62% (10-85%), respectively. Median follow-up was 31 months (95% CI: 22.6, NE), median OS was 48.1 months (95% CI: 48.1, NE) and 2-year OS probability was 0.89 (95% CI: 0.71, 1). Median metastases-free survival was 48.1 months (95% CI: 26.8, NE), median PFS was 22.4 months (95% CI: 15.6, NE) and 2-year PFS probability was 0.48 (0.26, 0.89).

Conclusion: Management of high-risk localised or locally advanced UTUC with MKP strategies was associated with good tolerance, preservation of renal function, and comparable PFS and OS to predicted in vulnerable patients. Prospective studies with more patients are needed to evaluate these possible benefits relative to current standards.

Competing Interests: The authors declare no relevant conflict of interest pertinent to this study. Full conflict of inflict disclosures include research funding from BMS, Eisai, EMD Serono for A.Y.S; Honoraria from Pfizer, Roche, BMS and Exelixis for A.Y.S; and Urogen Pharma (consultant) and Urology Education (speaker) for S.F.M. SFM: grant from QED therapeutics; consulting fees Merck, J&J; honoraria Ology education, Clinical Care Options. NN: consulting Schlesinger Group; Ad Board Aduro Bio Tech; Stock Allogene Therapeutics. AMK: grants Adolor, BMS, FKD Industries, FerGene, Heat Biologics, Merck, Photocure, SWOG, NIH/GU SPORE, AIBCCR, Janssen (+ Taris), Seattle Genetics; consulting Arquer Diagnostics. Asieris, Biological Dynamics, Bristol Myers Squibb, CG Oncology, H3 Biomedicine/Eisai, Engene, FerGene, Imagin Medical, Janssen, Medac, Merck, Photocure, ProTara, Seattle Genetics, Sessen Bio, Theralase, US Biotest, Urogen Inc., Roche, TMC Innovation; patents CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center; ad board: Arquer Diagnostics. Asieris, Biological Dynamics, Bristol Myers Squibb, CG Oncology, H3 Biomedicine/Eisai, Engene, FerGene, Imagin Medical, Janssen, Medac, Merck, Photocure, ProTara, Seattle Genetics, Sessen Bio, Theralase, US Biotest, Urogen Inc., Roche, TMC Innovation; leadership IBCG. MTC: grants or contracts ApricityHealth, Aravive, AstraZeneca, EMD Serono, Exelixis, Janssen, Pfizer; consulting Astellas, AXDev, AstraZeneca, Astellas, Exelixis, Eisai, EMD Serono, Exelixis, Genentech, Pfizer, SeaGen; honoraria Bristol Myers Squibb, Merck, Roche, Pfizer. AZ: grants or contracts Infinity pharma; consulting Amedo, Astra Zeneca, Bayer; honoraria Biocept, CancerNet, Incyte; other Janssen‐Cliag, McKesson Specialty Health, Pfizer. AOS: research grants or contracts: Basilea, Bristol Myers Squibb, Janssen, Merck Sharp and Dohme, Nektar Therapeutics; honoraria Janssen; Ad Board Astrazeneca, Basilea, Bavarian Nordic, Bristol‐Myers Squibb, Genentech, Ideaya Biosciences, Immunomedics, Janssen, LOXO‐Oncology, Merck sharp and Dohme, Mirati, Nektar Therapeutics, Seattle Genetics, Taiho.

(© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)