Presentation:
- 5-10% of renal tumors/masses are UTUC
- 2-5% of urothelial tumors occur in the upper tract (kidney and ureter)
- Peak incidence occurs between age 75-79
- Mean age at presentation: 65 (rare before age 40)
- Male: Female ratio 2:1
- Caucasian: Black ratio 2:1
- While the incidence of UTUC is rising, DSS is improving – but may be due to stage migration and earlier detection
- Symptoms:
- Hematuria (almost routinely)
- Flank pain
- The disease is often multifocal
- Presents with advanced disease
- 60% are invasive at diagnosis, 25% with regional Mets
Risk factors:
- Bladder cancer
- 2-4% incidence of UTUC in a patient with prior bladder urothelial carcinoma
- Increased with CIS, multifocality, etc.
- Contralateral UTUC
- 2-6% incidence
- Tobacco use
- Occupational exposure
- Cyclophosphamide
- Balkan nephropathy, NSAID abuse, Chinese herbal exposure (Aristolochia)
- Lynch syndrome (colon cancer, endometrial and UTUC)
Current management of UTUC has split down two pathways, depending on diagnostics tests – either management of low-risk (usually low-grade) UTUC or high-risk (usually high-grade UTUC). The management of low-risk UTUC is nephron-sparing surgery (endoscopic or minimally invasive) and the management of high-risk is nephroureterectomy.
- Yet, correctly identifying patients with low and high-risk disease is the challenge!
The current EAU guidelines published just last year have expanded the definition of low-risk UTUC to the following:
- Unifocal disease
- Tumor size < 2 cm (previously 1 cm)
- Low-grade urine cytology
- Low-grade URS biopsy pathology
- Non-invasive features on CTU (imaging)
For the rest of the talk, he focused on diagnostics and guideline recommendations.
Guidelines:
- Imaging (Strong level of evidence)
- CTU is the gold standard – has replaced IVU. Sensitivity and specificity exceed 95%.
- Lowest sensitivity for small tumors (but still around 89% for lesions < 5 mm, but only 40% for those < 3 mm)
- MRU if CTU not feasible due to renal function, etc.
- Staging for TNM requires CTU or MRU, though PET/CT may work
- Cystoscopy and urine cytology (strong level of evidence)
- Positive urine cytology is suggestive of UTUC in absence of bladder cancer/tumors or CIS
- Urine cytology detection yield is ~50-70% - but highly dependent on pathology at your institution and their experience!
- Depends on collection technique and sample handling too
- Has low sensitivity but high specificity
- Voided urine cytology – 23-92% accuracy
- Selective ureter cytology is much better – 77-100% accuracy
- Diagnostic URS
- The best approach to diagnose UTUC
- However can be technically challenging! Difficult to get a significant tissue sample
- He recommends basketing tumor (push away from you rather than pulling towards the scope) to get the best tissue sample
- Best efficacy when you use smaller instruments, digital scopes, and multifunctional graspers
- Increased deflection is key to access and survey the most of the upper tract
- Major pitfalls of URS and biopsy:
- Insufficient sample
- Sampling error
- Difficulties in sampling muscle and deeper tissue
- False positive after instrumentation
- Misinterpretation
He did briefly talk about other diagnostic tools, including:
1) FISH – fluorescence in-situ hybridization
- Most experienced members in the audience did NOT use this regularly, but added it only in difficult cases where routine evaluation (cysto, cytology) was inconclusive
- Useful for suspicious imaging but negative cytology
2) Immuno-Cyt - no one in the audience really used this
3) PDD – enhancing endoscopic imaging with instillation of photodynamic agents
- Increases visual diagnostic yield ~37%
- It is more sensitive and specific than white light imaging
- This may lead to better, more complete therapeutic effect – and subsequent lower recurrence rates, similar to bladder cancer results
- However, most of the audience members primarily use this for bladder cancer and not the upper tract
4) Narrowband imaging (NBI) at the time of URS
- Dr. de la Rosette insists that be used during every URS
- Additional tumor diagnosis ~14%, detection of extended limits of tumor ~9%
- The greatest benefit in newly diagnostic UTUC, ~38%
5) OCT – optical coherence tomography
- Expensive technology, but has lots of potential
- Introduction of a narrow probe via the URS into the lumen of the ureter
- Based on light scattering, it provides very detailed staging information (re: depth) in a live situation
- AUC is 0.92! to predict low vs. high-grade disease
- It has 83% concordance with histopathology, 100% sensitivity, and 92% specificity
- Limitations: large, exophytic tumors, CIS and inflammation
6) CLE – Confocal Laser Endomicroscopy
- Another new, expensive technology with lots of potential
- Ultrahigh resolution microscopy in real-time, in vivo
- Provides detail regarding microscopic architecture and therefore can be very useful for grade evaluation
All these new imaging techniques need validation, however, and should be used primarily in a clinical trial or academic settings at this time.
From a diagnostic standpoint, there is lots of established data looking at the discrepancy between biopsy grade/stage and final biopsy grade/stage.
- The biopsies ability to predict grade is poor, especially for higher grade
- 37-96% upgrading on final nephroureterectomy pathology in most studies
- 29-36% upstaging on final nephroureterectomy pathology in most studies
- This makes accurate management of patients difficult, as Dr. Khochikar notes in his next talk on conservative management
Presented by: Jean de la Rosette, MD, Professor, and Chairman of the Department of Urology, at AMC University Hospital in Amsterdam, the Netherlands
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