Indications, current endoscopic management, adjuvant therapies, and follow-up regimens in renal conservational management of upper urinary tract transitional cell carcinoma (UUTT) are described.
This short review emphasises contemporary endoscopic diagnostic and therapeutic ablative options and includes information about adjuvant therapies and surveillance protocols in patients with low- or intermediate-risk UUTT selected for renal conservation.
Evidence was acquired from a review of the recent published literature over the past 15 yr, with key articles selected from expert centres.
Key points from cited articles were summarised in the review and blended with new material based on emerging techniques and technology along with expert experience.
The major findings of this review suggest that when optimally performed using a meticulous technique with appropriate equipment both for diagnosis and treatment in expert centres, safe renal conservation is possible in a defined UUTT population, even when a normal contralateral kidney is present. A strong case can be made for challenging the age-old paradigm that nephroureterectomy should be uniformly applied as the first-line treatment for all patients with suspicious filling defects in the upper urinary tract or proven clinically localised UUTT, provided there is no high grade-stage, or an imperative for renal preservation.
Keywords: Upper tract, Urothelial tumour, Endourologic, Renal conservation, Technological advances.
Nephroureterectomy continues to be generally considered as the gold standard in the treatment of high-grade and high-stage urothelial tumours in the upper urinary tract (UUT). In the last decade, a technological revolution has fuelled the growth of advanced capability endoscopes and complementary retrograde intrarenal surgical techniques. Consequently, there has been steady growth of and reproducible success for endourologic diagnosis and treatment of low- to intermediate-risk UUT transitional cell carcinoma (UUTT) in expert hands, thus sparking a timely and important debate about renal preservation in selected patients with a normal contralateral UUT  and . Moreover, where renal function is compromised, either anatomically or functionally, there is an imperative for organ preservation whenever possible, due to both the expense and the negative quality-of-life impact of renal replacement therapy such as dialysis with its associated morbidity and mortality .
2. Examination of the upper urinary tract
Concurrent tumours of the bladder, if present, should be resected first wherever possible, especially if large or suspicious for high-grade or muscle invasion, because these tumours are often the cause of metastases, and if the tumours are high grade (which have a higher propensity for loss of cell to cell wall adhesion), they may contaminate cytology wash samples obtained later from the UUT. The rationale for dealing with low- to intermediate-grade and -stage UUTT with renal conservation in the presence of a normal upper tract is recognition (1) that few of these patients will have more than superficial disease (the majority, just as with bladder cancer) and will progress to metastatic disease; (2) that even fewer will die of disease; (3) that tumours in the upper tract can be accessed readily, biopsied, and eradicated comprehensively using contemporary equipment, with low risk of tumour cell spillage outside the collecting system; (4) that field instability leading to recurrence can be stabilised with topical adjuvant therapies; and (5) that the minority that do progress will be picked up in a timely fashion at the point of progression in grade or stage and be amenable to curative extirpative surgery. Consequently, rigorous endoscopic lifelong surveillance is requisite because most of these patients have been smokers for many years, and although cessation reduces risk somewhat, it is not entirely eradicated. The clarity of endoscopic vision is essential to have a chance of treating the lesions with precision. Any urothelial wall perforation must be avoided so tumour cells are not spilled outside the confines of the upper tract. This task requires a delicate touch in a mobile structure with complex intrarenal anatomy.
2.1. Semirigid ureteroscope
Whenever possible, a semirigid ureteroscope is preferred for the initial inspection of the upper tract because of the better view and the bigger working channel that can accommodate larger accessories such as ≥4-F cup biopsy forceps and a 365-μm laser fibre that can safely transmit more energy for tumour ablation (useful for larger lesions). Tumour sampling with a combination of ureteroscopic cytology washings and biopsy is essential to establish the tumour grade (which has a good correlation to tumour stage) and to rule out high-grade lesions, which have a higher propensity for metastasis. By ensuring that the ureter is clear of tumour, it is then possible to place a ureteral access sheath, which not only permits easy and repeated access to the upper tract but also maintains a low intrarenal pressure by allowing urine and irrigant efflux alongside the endoscope and keeps the risk of tumour cell seeding at its lowest.
2.2. Flexible ureterorenoscope
In the kidney, beyond the upper calyx and medial wall of the renal pelvis, a flexible ureterorenoscope has to be used in conjunction with a 200-μm quartz laser fibre to minimise both the risk of instrument damage and the loss of instrument tip deflectability. Flexible ureterorenoscopes can be a mixture of fibreoptic dual-active deflection instruments and newer generation digital “chip in the tip” instruments (both complementary metal oxide semiconductor [CMOS] and CCD [charge-coupled device] chips). The CCD technology platform also provides additional capability for diagnostic enhancement through narrow band imaging, which highlights areas of abnormal vascularity. Further assessment of the true contribution of this new technology versus other modalities such as blue light photodynamic diagnosis with instilled photosensitisers of neovascularity such as hexaminolevulinate (Hexvix) is awaited at this time because they are not yet widely available beyond the bladder.
The technique used for UUT access should be standardised with parenteral antibiotic prophylaxis, cystoscopy, and fluoroscopic-guided placement of a safety Bentson 0.035-in floppy-tipped safety guidewire; intravenous administration of furosemide to induce diuresis and prevent pyelovenous reflux; use of a working guidewire to achieve optical dilation of the ureteral orifice before obtaining ureteroscopic urine wash specimens for selective cytology; and placement of a ureteral access sheath with a lumen at least 2 F for irrigant efflux and maintenance of low intrarenal pressures. After multiple cup biopsies (>2–6), initial coagulation prevents or reduces tumour bleeding, and tumour base ablation should be performed, as previously described by some of our group . Biopsy specimens can be obtained with a 4.6-F reusable rigid forceps, if a semirigid instrument is used, or either a 3-F flexible cup forceps or nitinol basket (used to avulse portions of papillary tumour), if a flexible instrument is used. Pathologists analysing such small specimens should be specialised in this delicate work and should work in very close conjunction with cytopathologists and the endourologist for maximum diagnostic gain in a multidisciplinary setting where the endourologist/endo-oncologist is the heart of the team. Newer devices such as the Bigopsy (7.5F cup with 2.4F shaft; Cook Urological Inc, Spencer, IN, USA), which can be backloaded into the flexible ureterorenoscope work channel, offer prospects of yielding more tissue for robust pathologic analysis of grade and stage, but it has yet to be widely tested in adequately sized series in expert centres and may be difficult to deploy in the lower calyces due to limitation of scope tip deflection.
Since its introduction to urologic practice in 1995 , the holmium:yttrium aluminium garnet (YAG) laser combination has quickly replaced a 3-F Bugbee electrode and become the cornerstone of endourologic management of UUTT ablation. This laser delivers pulsed holmium energy of shallow penetration (0.4
Aftercare is provided by placement of a D-J stent at the end of the procedure. This can be removed in the office under local anaesthesia after 1 wk unless a second look is deemed necessary (for tumours >1.5
If the tumour cannot be reached for biopsy or ablation due to location in the lower calyx (especially the medial part) or because it is too large and vascular for ureterorenoscopic ablation, percutaneous resection may be needed. This is contraindicated for high-grade tumours (where seeding of tumour cells outside the collecting system is a real risk), where cytology wash is usually a reliable guide if it is not possible to obtain biopsy material. Sterile water should be used as an irrigant for monopolar percutaneous loop resection or electrovaporisation, due to its cytolytic effect, whereas saline is used for bipolar or plasma kinetic resection or vaporisation. The latter has the advantage of superficial thermal tissue penetration akin to the holmium and thulium lasers. There is a theoretical risk of tumour cell seeding into the renal access tract, but experience with adjuvant tract irradiation is limited .
In the series with the longest published follow-up to date, retrospective chart review demonstrated slightly less but little overall difference between bladder and upper tract recurrence-free survival . Regular long-term endoscopic surveillance of both the upper and lower urinary tracts is therefore mandatory after successful endoscopic UUTT treatment and is feasible. It may even be performed for the affected upper tract with local anaesthesia in the bladder in selected cases (pers. comm., A. Patel and G.J. Fuchs, London, UK).
Adjuvant therapies have been used in the UUT, just as with the bladder, for higher risk superficial disease to try to prevent recurrence or progression but with a lack of uniformity as to dose and instilled volume, whereas it is much harder to control contact time with upper tract instillations. In almost all cases, patient numbers are too small and follow-up is too short in any single series published to date to make reliable evidence-based conclusions about their true value. But just as with the bladder, the short-term response rates and recurrence-free survival are consistently higher with bacillus Calmette-Guérin compared with mitomycin (the two most common agents), although this is counterbalanced by greater potential local and systemic morbidity (again, akin to the bladder).
The high risk of both bladder and upper tract recurrence in this selected patient population mandates that follow-up should be endoscopic in conjunction with cytology washings of both lower and ipsilateral upper tracts rather than radiographic (because the latter has low sensitivity) and should follow the regimen prescribed in the European Association of Urology guidelines for high-risk superficial disease of the bladder. Because recurrences are most common in the first year both in the bladder and in the upper tract, it has been our routine practice to perform monthly ureteroscopic surveillance every 3 mo for the first year, especially if initial tumour is not low grade, ≥1.5
Conflicts of interest
The author has nothing to disclose.
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© 2010 European Association of Urology, Published by Elsevier B.V.