Upper Tract Urothelial Carcinoma in the Lynch Syndrome Tumour Spectrum: A Comprehensive Overview from the European Association of Urology-Young Academic Urologists and the Global Society of Rare Genitourinary Tumors

Context: Upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy in Lynch syndrome (LS). Objective: To systematically review the available literature focused on incidence, diag-nosis, clinicopathological features, oncological outcomes, and screening protocols for UTUC among LS patients. Evidence acquisition: Medline, Scopus, Google Scholar, and Cochrane Database of Systematic Reviews were searched up to May 2021. Risk of bias was determined using the modified Cochrane tool. A narrative synthesis was undertaken. Evidence synthesis: Overall, 43 studies between 1996 and 2020 were included. LS patients exhibited a 14-fold increased risk of UTUC compared with the general popula-tion, which further increased to 75-fold among hMSH2 mutation carriers. Patients younger than 65 yr and patients with personal or family history of LS-related cancers should be referred to molecular testing on tumour specimen and subsequent genetic test-ing to confirm LS. Newly diagnosed LS patients may benefit from a multidisciplinary man-agement team including gastroenterologist and gynaecologist specialists, while genetic counselling should be recommended to first-degree relatives (FDRs). Compared with sporadic UTUC individuals, LS patients were significantly younger (p = 0.005) and exhib-ited a prevalent ureteral location (p = 0.01). Radical nephroureterectomy was performed in 75% of patients (5-yr cancer-specific survival: 91%). No consensus on screening proto-cols for UTUC was achieved: starting age varied between 25-35 and 50 yr, while urinary cytology showed sensitivity of 29% and was not recommended for screening. Conclusions: Urologists should recognise patients at high risk for LS and address them to a comprehensive diagnostic pathway, including molecular and genetic testing. Newly diagnosed LS patients should be referred to a multidisciplinary team, while genetic coun-selling should be recommended to FDRs. Patient summary: In this systematic review, we analysed the existing literature focused on upper tract urothelial carcinoma (UTUC) among patients with Lynch syndrome (LS). Our purpose is to provide a comprehensive overview of LS-related UTUC to reduce mis-diagnosis and improve patient prognosis.(c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Automated summary

This article provides a systematic review of upper tract urothelial carcinoma (UTUC) among patients with Lynch syndrome (LS), covering incidence, diagnosis, clinicopathological features, oncological outcomes, and screening protocols. LS patients have a significantly increased risk of UTUC compared to the general population, and they tend to be diagnosed at a younger age. Comprehensive management including multidisciplinary teams and genetic counseling should be implemented for the diagnosis and treatment of LS patients.