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

Eur Urol Oncol. 2022 Feb;5(1):30-41. doi: 10.1016/j.euo.2021.11.001. Epub 2021 Dec 9.


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% of patients (5-yr cancer-specific survival: 91%). No consensus on screening protocols 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 counselling 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 misdiagnosis and improve patient prognosis.

Keywords: EAU Young Academic Urologists; Global Society of Rare Genitourinary Tumors; Hereditary nonpolyposis colorectal cancer; Lynch syndrome; Mismatch repair; Upper tract urothelial carcinoma.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / genetics
  • Carcinoma, Transitional Cell* / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
  • Female
  • Humans
  • Male
  • Urinary Bladder Neoplasms*
  • Urologists
  • Urology*