Background/Objectives: The aim of this study is the presentation of an endoscopic therapeutic approach for three patients with a solitary kidney who were diagnosed with urothelial cancer of the upper tract. Methods: This retrospective analysis included patients with solitary kidneys who suffered from high-grade UTUC (urothelial cancer of the upper urinary tract) and underwent conservative treatment. Results: The first patient was a 67-year-old male who had a prior history of a nephroureterectomy due to UTUC six years ago. The patient was diagnosed with high-grade UTUC in the contralateral kidney. The tumor has been managed with endoscopic ablation. The second patient was a 74-year-old male with a non-functional kidney and high-grade UTUC diagnosed in the contralateral side. The patient underwent endoscopic ablation for the tumor. The third case was a 68-year-old female patient who had a history of a nephroureterectomy due to UTUC. Afterward, she was diagnosed with high-grade UTUC in the contralateral kidney. The patient was treated with percutaneous tumor resection and the placement of a nephrostomy tube. The first patient was included in an immunotherapy program based on an oncologist consultation after laser ablation treatment for Ta high-grade UTUC, followed by the endoscopic management of two recurrences. Afterward, no recurrence was detected. The remaining two patients followed up without the detection of a new recurrence. Conclusions: The kidney-sparing approach (tumor laser ablation or resection) for high-risk UTUC treatment in selected patients with solitary kidneys seems to provide adequate early outcomes in relation to preserving renal function and effective disease management. It is important to personalize the way of treatment in every case after a thorough examination of the patient’s data.
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