The current standard for UTUC diagnosis, stratification and surveillance are CT Urogram + diagnostic ureteroscopy (dURS) + urinary cytology. But, these are invasive, time consuming, expensive and still miss many lesions. Hence, adding appropriate markers may help reduce invasiveness, reduce cost and improve detection rates. Specifically, they may:
- Detect UTUC early in at-risk populations, leading to improved survival
- Help better risk stratify (AA exposure, Lynch syndrome, prior bladder cancer), leading to kidney sparing
- Reduce frequency of testing after KSS, improving quality and length of life
- Missing cancer, which may lead to increased mortality
- Inaccurate risk stratification, which may lead to increased mortality
- False positives, which may lead to increased anxiety and unnecessary/costly work-up
Urine Cytology – role in 2018?
- Positive cytology suggestive of UTUC if cystoscopy negative and no evidence of CIS in bladder/prostatic urethra
- Cytology is less accurate in setting of UTUC than bladder cancer
- Positive cytology is still suggestive of high grade disease
- However, PPV of high-grade disease is still not very high, so much be combined with other factors for risk stratification
- NPV is very high (63-99%), but only in 2 studies
- Not useful for surveillance in low-grade patients
- Sensitivity is poor, ranging from 27-80%
- NPV is highly variable (67-88%), but only 3 studies
- Also not useful for surveillance in low-risk patients
- Sensitivity is 33-75%
Interestingly, sensitivity is higher in patients after RC for invasive bladder cancer
Urinary FISH (fluorescence in-situ hybridization)
- Still preliminary
- NPV highly variables (50-100%)
- Sensitivity 50-100%
- Not useful in surveillance for low-risk disease
Aristocholic acid, an agent found in Asian herbal medications, has been associated with UTUC and urothelial disease.
Leung Chem. Toxic. 2015 – may have identified a method to utilize liquid chromatography/MS to assess urine of patients for AA exposure.
Lynch Syndome
UTUC is a recognized high-frequency presentation of Lynch syndrome (HNPCC), which a cumulative risk of 1-28% during a patient’s lifetime. It is second only to endometrial and stomach cancer.
Up to 10-20% of UTUC are thought to be Lynch syndrome related
There are clear clinical predictors of having Lynch syndrome, that should be assessed in all patients with UTUC (Roupret EAU guidelines 2018)
His last point – there are 0 STUDIES for the role of urinary biomarkers for patients on surveillance following kidney sparing surgeries.
Final take-home points:
- No ideal marker
- No single marker has clinical superiority to dURS
- Cytology is the only one that seems to be accepted and used regularly – ureteral washing seems to be superior to voided
- Panel of markers will be necessary – due to tumor heterogeneity
- Bladder urinary markers cannot be extrapolated to UTUC disease
- Select appropriate marker for specific clinical scenarios according to clinical needs
Presented by: S. Shariat, Vienna, Austria
Written by: Thenappan Chandrasekar, MD Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark