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.

Upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy in Lynch syndrome (LS).

To systematically review the available literature focused on incidence, diagnosis, clinicopathological features, oncological outcomes, and screening protocols for UTUC among LS patients.

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.

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.

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.

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.

European urology oncology. 2021 Dec 09 [Epub ahead of print]

Chiara Lonati, Andrea Necchi, Juan Gómez Rivas, Luca Afferi, Ekaterina Laukhtina, Alberto Martini, Eugenio Ventimiglia, Renzo Colombo, Giorgio Gandaglia, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Agostino Mattei, Claudio Simeone, Maria I Carlo, Shahrokh F Shariat, Philippe E Spiess, Marco Moschini, European Association of Urology Young Academic Urologists EAU-YAU: Urothelial Carcinoma Working Group, the Global Society of Rare Genitourinary Tumors GSRGT

Department of Urology, Spedali Civili di Brescia, Brescia, Italy; Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland. Electronic address: ., University Vita-Salute San Raffaele, Milan, Italy; Department of Medical Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, Clinico San Carlos Hospital, Madrid, Spain., Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., University Vita-Salute San Raffaele, Milan, Italy; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, Spedali Civili di Brescia, Brescia, Italy., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic., Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.