Research Progress on Urological Tumors Associated with Lynch Syndrome

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome, caused by germline pathogenic variants in the DNA mismatch repair (MMR) system. Beyond colorectal and endometrial cancers, the spectrum of tumor associated with LS has expanded to the urological system. Upper urinary tract urothelial carcinoma (UTUC) represents the most frequent LS-associated urological cancer and is typically characterized by microsatellite instability-high/mismatch repair-deficient(MSI-H/dMMR) status and high tumor mutational burden (TMB), showing a high sensitivity to immunotherapy. Bladder and prostate cancers also show increased incidence among specific LS genotypes. In recent years, the integration of multi-omics analyses, liquid biopsy, artificial intelligence, and disease risk prediction models has advanced understanding of LS-associated urological tumors in terms of molecular mechanisms, early detection, and precision therapy. Immune checkpoint inhibitors demonstrate remarkable efficacy, particularly in dMMR/MSI-H UTUC. Future efforts should focus on establishing systematic screening strategies, optimizing individualized treatment, and conducting multicenter prospective studies to improve early diagnosis and clinical outcomes in high-risk populations. This review summarizes recent research progress on urological tumors associated with LS to enhance clinical understanding of the disease.