Organ-Preserving Management of Primary Lynch Syndrome–Associated High-Grade Upper Tract Urothelial Carcinoma Using Gemcitabine–Cisplatin and Pembrolizumab: First Reported Case Worldwide

Abstract Lynch syndrome (LS), caused by germline mismatch-repair mutations, increases the risk of upper tract urothelial carcinoma (UTUC), for which radical nephroureterectomy is the standard treatment. Non-surgical curative management has not been described previously. We report a 48-year-old man with MSH2-associated LS who presented with a 3.5 cm distal ureteric high-grade UTUC. To preserve renal function, multidisciplinary consensus favoured systemic therapy over surgery. He received gemcitabine–cisplatin for six cycles followed by pembrolizumab for two years, achieving complete metabolic response on PET-CT. He remains disease-free at one year. This case demonstrates successful organ-preserving treatment of hereditary UTUC.