| Sumario: | Simple Summary: Upper tract urothelial carcinoma is a rare and aggressive cancer that typically spreads to the lungs, bones, liver, or distant lymph nodes but rarely to the gastrointestinal tract. This report describes the first known case of such a cancer originating in the left ureter and metastasizing to the descending colon 19 months after surgical removal of the ureter. Despite initial responses to platinum-based chemotherapy, the disease progressed quickly during follow-up immunotherapy, leading to the patient's death from complications. These findings emphasize that the colon can be an unusual site of spread, highlighting the need for biopsy confirmation to distinguish it from primary colon cancer and for close monitoring to enable timely shifts to advanced therapies like targeted drugs, potentially improving outcomes in similar rare cases. Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations.
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