open access: (Lynch Syndrome) A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis

A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool

 "Based on the most recent European Association of Urology (EAU) guidelines on UUT-UC, a hereditary tumour has to be suspected if the patient is less than 60 years of age or has a personal or family history of an HNPCC-associated cancer [9]. The aim of this study was to analyse the demographic and epidemiological factors that are associated with a suspicion of hereditary UUT-UC in a large cohort from a national collaborative group."

 DISCUSSION

"Although UUT-UCs are rare, with an annual estimated incidence in western countries of approximately one or two new cases per 100 000 inhabitants [9], epidemiological data demonstrate that in patients with HNPCC syndrome the cumulative risk of UUT-UC ranges up to 6% [3]. Watson et al. [3] reported a 22-fold increased risk compared with the general population. This may even represent an underestimation as the authors did not consider UUT-UCs of the renal pelvis together with those of the ureter. To our knowledge, there are few publications investigating the risk of having an HNPCC tumour among patients with UUT-UC [4,7]....."

What's known on the subject? and What does the study add?

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant multi-organ cancer syndrome. Upper urinary tract urothelial carcinomas belong to HNPCC-related tumours and rank third within this group after colorectal and endometrial cancer. However, many urologists are not aware of this association and it is presumed that some hereditary cancers are misclassified as sporadic and that their incidence is underestimated. Consequently, family members of patients with upper urinary tract urothelial carcinomas secondary to HNPCC may be denied appropriate surveillance and early detection.

A significant proportion of patients (21.3%) with newly diagnosed upper urinary tract urothelial carcinomas may have underlying HNPCC.

Demographic and epidemiological characteristics suggest different mechanisms of carcinogenesis among this population.
Recognition of such potential is essential for appropriate clinical and genetic management of patients and family. In order to help to identify these patients, we propose a patient-specific checklist.

OBJECTIVE

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  To identify, based on previously described clinical criteria, hereditary upper urinary tract urothelial carcinomas (UUT-UCs) that are likely to be misclassified as sporadic although they may belong to the spectrum of hereditary non-polyposis colorectal cancer (HNPCC) associated cancers.

PATIENTS AND METHODS

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  We identified, using established clinical criteria, suspected hereditary UUT-UC among 1122 patients included in the French national database for UUT-UC.
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  Patients were considered at risk for hereditary status in the following situations: age at diagnosis <60 years with no previous history of bladder cancer; previous history of HNPCC-related cancer regardless of age; one first-degree relative with HNPCC-related cancer diagnosed before 50 years of age or two first-degree relatives diagnosed regardless of age.

RESULTS

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  Overall, 239 patients (21.3%) were considered to be at risk of hereditary UUT-UC.
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  Compared with sporadic cases, hereditary cases are more likely to be female (P= 0.047) with less exposure to tobacco (P= 0.012) and occupational carcinogens (P= 0.037). A greater proportion of tumours were located in the renal pelvis (54.5% vs 48.4%; P= 0.026) and were lower grade (40% vs 30.1%; P= 0.015) in the hereditary cohort.
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  The overall, cancer-specific and recurrence-free survival rates were similar in both cohorts.
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  We propose a patient-specific risk identification tool.

CONCLUSIONS

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  A significant proportion (21.3%) of patients with newly diagnosed UUT-UC may have underlying HNPCC as a cause.
• • 
  Recognition of such potential and application of a patient-specific checklist upon diagnosis will allow identification and appropriate clinical and genetic management for patient and family.