SUO 2015 Lynch Syndrome in UTUC: Significance, Screening, and Surveillance

In today’s second symposium on upper tract urothelial carcinoma, Dr. Morgan Roupret discussed his group’s work on Lynch syndrome, including recommendations for screening and surveillance. Lynch syndrome, also known as Hereditary Non-Polyposis Colon Cancer (HNPCC) is the most common hereditary cause of colorectal cancer, accounting for 7% of such tumors.
Disease features include young age at diagnosis (median age is 44 vs 65 yo in non-hereditary cases) and autosomal dominant transmission. Upper tract urothelial carcinoma (UTUC) is often a presenting finding, and patients have a 6% lifetime risk of developing disease (22x higher than that of the general population).
Screening is a key issue in identifying patients with UTUC who may have Lynch Syndrome. Amsterdam II criteria includes 3 relatives with HNPCC, of whom one is a first degree relative, 2 successive generations are affected, and one is diagnosed before the age of 50. Review of these criteria has shown a diagnosis rate of only 5% with this screening protocol. Dr. Roupret’s group reviewed a French national database and found that hereditary cases of UTUC were more likely to be female, less associated with smoking history, and were more likely to be low grade cancers in the renal pelvis; OS and CSS were similar between hereditary and sporadic cases. Based on these findings, the group proposed a checklist to identify patients at risk for hereditary disease, which had a 21% success rate in the study (see figure below) (Audenet et al, BJUI 2012).
Despite adequate early diagnosis through effective screening, continued surveillance of these patients is vital as recurrence is common. Archer and colleagues recommended a surveillance schema based on family history. Their work concluded that high risk patients (those with prior personal history of urothelial Ca) should get annual urine cytology, NMP22, and dipstick, along with annual contrast CT and cystoscopy. Depending on the histological variant, more frequent surveillance may be necessary. Further treatment of these patients hinges on adequate family history and attention to other potential disease sites, as well as addressing the need for Surgical Oncology, Gynecology, Dermatology, and Genetics referrals.
Finally, it is important to identify microsatellite instability, as this can impact chemotherapeutic response.

Presented by:
Dr. Morgan Roupret, MD, PhD
Pitie-Salpetriere Hospital
Reported by:
Dr. Nikhil Waingankar,MD from the 2015 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" December 2 - 4 Washington, DC USA
Fox Chase Cancer Center, Philadelphia, PA USA