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

Abstract

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, diagnosis, 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 population, 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 testing to confirm LS. Newly diagnosed LS patients may benefit from a multidisciplinary management 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 exhibited a prevalent ureteral location (p = 0.01). Radical nephroureterectomy was performed in 75%

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

“…These observations appear consistent with the conclusions of a recent review from the European Association of Urology, Young Academic Urologists and the Global Society of Rare Genitourinary Tumors. 14 The potential benefits of urological surveillance for patients with LS, particularly for path_MSH2 carriers, merit further research.…”

“…There is a lack of evidence that surveillance prevents extracolonic cancers, but current guidelines do include surveillance recommendations for some of the many extracolonic cancers associated with LS. 10 , 13 , 14 , 15 , 16 There is limited information on CRC and extracolonic cancer mortality in path_MMR carriers who receive colonoscopy surveillance. Providing new data on mortality was the focus of this study.…”

Teenage-Onset Colorectal Cancers in a Digenic Cancer Predisposition Syndrome Provide Clues for the Interaction between Mismatch Repair and Polymerase δ Proofreading Deficiency in Tumorigenesis

“…Our index patient and the patient described by Berrino et al [ 54 ] had urothelial carcinoma, a cancer entity that has so far not been described in PPAP [ 15 ] but has been in LS, albeit very rarely in PMS2 PV carriers [ 36 ]. Urinary tract cancer surveillance is controversial due to uncertain screening method effectiveness in the context of LS [ 56 ]. If offered, it should probably start when the patient is a teenager, given the diagnosis at the age of 19 years in the patient of Berrino et al [ 54 ], and should be performed in a clinical trial of an LS expert center [ 57 ].…”

Upper Tract Urothelial Carcinoma: A Narrative Review of Current Surveillance Strategies for Non-Metastatic Disease

“…Although Lynch syndrome patients are at higher risk of developing UTUC [ 14 ], high microsatellite instability (MSI), which is a screening tool for Lynch syndrome in UTUC patients, seems to be associated with better overall survival [ 15 ].…”