Ureteral fistula manifesting as unexplained ascites during treatment with immunotherapy in POLE‑mutated metastatic colorectal cancer: A case report

DNA polymerase ε (POLE) proofreading-deficient variants (POLE-pds) are rare in metastatic colorectal cancer (mCRC) but may predict high sensitivity to immune checkpoint inhibitors.Tumors invading the hollow viscera can develop fistulas due to treatment-induced necrosis.However, immunotherapy-associated ureteral fistulas may present atypically.The current study describes the case of a 52-year-old male patient with mCRC harboring the POLE P286R mutation.After second-line therapy failure, the patient received penpulimab plus anlotinib.Following four treatment cycles, the patient developed unexplained ascites and peritoneal thickening, which were initially considered to potentially indicate disease progression or immune-related adverse events.A ureteral tumor fistula was identified 3 months later; the ascites-to-serum creatinine ratio (3.4:1) and resolution after nephrostomy confirmed urinary leakage.Notably, the patient achieved sustained clinical complete remission for >2.5 years without further antitumor therapy.Ureteral fistulas presenting as ascites are a diagnostically challenging complication during treatment with immunotherapy.Early recognition and conservative management via nephrostomy can be effective and patients with POLE-pd mCRC can achieve durable remission despite such complications.Trial registration no.NCT04970914;