Noninvasive diagnosis

Radiologic studies, including intravenous contrast studies to outline the collecting system with excretory urography or computed tomography (CT) urography are the most useful noninvasive diagnostic techniques. A filling defect is the most common finding, which may indicate an upper tract urothelial neoplasm. The differential diagnosis includes blood clot, lucent calculus, air bubble, fungus ball, sloughed papilla, external compression with a crossing vessel, or benign inflammatory or neoplastic lesion. One series using a multidetector CT scanner for CT urography in patients with gross hematuria demonstrated a very high sensitivity, specificity, and accuracy [10]. In some patients with a severe contrast allergy with nonvisualization of the collecting system, retrograde ureteropyelography may be indicated. However, this suffers from low accuracy [4, 11].

Renal ultrasound can define intrarenal calculi, hydronephrosis, and renal masses accurately but is less useful to define small intraluminal soft tissue masses. In contrast, CT can accurately distinguish calculi from soft tissue masses. It is also helpful in demonstrating masses extending beyond the collecting system or enlarged lymph nodes. Inclusion of a pyelographic phase with reconstruction of the excretory system or an abdominal radiograph taken after the administration of contrast as an anteroposterior ureteropyelogram may be most useful in demonstrating intraluminal lesions [10, 12]. Magnetic resonance imaging has similar limitations, especially in the cross‐sectional mode [13]. The magnetic resonance urogram designed to image the fluid of a distended collecting system may be helpful in some patients with nonfunctioning kidneys or severe contrast allergies.

Cytologic study of voided urinary samples is of limited value because of the frequent equivocal and false negative findings. It can be useful in detecting high‐grade tumors, which shed obviously malignant cells in the urine. The sensitivity of voided urinary cytology increases with an increasing grade, ranging from 11% for Grade 1 to 83% for Grade 4 lesions [14]. Elective ureteral catheterization for a specific and localized upper tract urinary sample for cytologic study is occasionally indicated in patients with positive cytology without radiographic findings and with normal cystoscopy and bladder biopsy. However, routine ureteral catheterization to collect urine from a radiographically abnormal area is no longer indicated if ureteroscopy can be performed. Similarly, fluoroscopic guided brush biopsy is rarely indicated when ureteroscopy is available.

Fluorescence in situ hybridization (FISH) has been used to detect genetic aberrations in chromosomes 3, 7, 9, and 17 and improves the sensitivity of voided urine cytology for all bladder lesions, including low grade, from 25 to 53% [15, 16]. The appeal of FISH would be to utilize it in voided urine specimens to detect UTUC without the invasiveness of ureteroscopy. The largest published reports of FISH in UTUC detection using voided urine specimens demonstrate increased sensitivity compared to voided cytology but it is still not sensitive enough to forgo ureteroscopic visualization for diagnosis [17–19].

Endoscopic diagnostic techniques

Endoscopic evaluation of an abnormality in the upper urinary tract suspicious for a neoplasm includes inspection of the entire bladder and involved collecting system. Cystoscopy is an essential evaluation of the patient with hematuria and/or filling defects because of the risk of associated bladder tumors and to provide access to the ureter for retrograde pyelography and ureteroscopy. A retrograde ureteropyelogram may give more information regarding the extent of the filling defect or suspicious lesion or ureteral abnormalities, which might affect access for treatment. A cone‐tipped retrograde injection most efficiently outlines the entire collecting system without traumatizing the ureter itself. Care should be taken to prevent overfilling of the collecting system, which can obscure filling defects. Initial ureteral catheterization without contrast study should be avoided since it can traumatize the specific lesion of interest and the otherwise normal ureteral mucosa.

A “no‐touch technique” should be employed to examine the involved upper collecting system. The distal ureter is first inspected either with a small rigid endoscope, preferably one small enough to pass into the orifice without other dilation, or with a flexible ureteroscope that can be passed into the ureter without dilation [20]. In this way, the ureter can be inspected without prior instrument trauma. When using a semirigid ureteroscope, it is passed as far as possible into the lumen before leaving a guidewire in place as the endoscope is removed. The guidewire is passed only to the level of the ureter that has been inspected with the semirigid ureteroscope and should not be passed into the intrarenal collecting system where the tip of the wire can traumatize the calyx or the renal pelvis and obscure subsequent visual inspection. The smallest flexible ureteroscope is then passed over the guidewire into the ureter. If a small flexible ureteroscope can be passed directly into the ureter, then the steps of semirigid ureteroscopy and wire placement can be avoided.

The flexible ureteroscope is used to inspect the more proximal portions of the ureter not previously seen and the intrarenal collecting system. Inspection at that level should be systematic going from the renal pelvis to the upper infundibula and calyces to the mid and then the lower pole. In this way, the risk of trauma to the mucosa with the endoscope is minimized.

Continuous irrigation with saline is maintained through the working channel of the ureteroscope to clear the field of view. Iodinated contrast medium can be used in the irrigant to outline the collecting system for fluoroscopic monitoring. Positioning of the flexible ureteroscope throughout the collecting system can then be confirmed fluoroscopically. Care must be taken to avoid overfilling the collecting system, since this can induce submucosal hemorrhage and rupture of the fornices. When adding contrast through the endoscope within the collecting system, the irrigant present should be removed. Lines of refraction will be visible as fluids of two different densities mix. This can be avoided by minimizing the mixing.

If there is a specific lesion to be examined, such as a filling defect or a point of obstruction, then the distal portion of the urinary tract should be inspected first, followed by the lesion itself in order to inspect it within a clear visual field without other manipulation that may cause bleeding and obscure the field of view. In many cases, visual inspection alone can provide a diagnosis [21–24]. For example, the appearance of a calculus will readily distinguish it from a low‐grade papillary tumor. Irrigant with contrast should be used so that fluoroscopy can demonstrate the tip of the ureteroscope at the filling defect. In this way, correct visualization and identification of the lesion can be confirmed.

Epithelial neoplasms may have totally different appearances. Low‐grade UTUC has a typical papillary appearance, similar to the same lesions in the bladder (see Videos 50.1, 50.2a,c, and 50.3 ). High‐grade UTUC may be more sessile and less papillary, often with necrotic or inflammatory debris on the surface. However, these differences are not consistent. El‐Hakim and colleagues [25] found an accuracy of only 70% in determining the grade of an upper tract neoplasm by appearance alone.

Benign lesions can often be diagnosed endoscopically. Fibroepithelial polyps located within the pelvis and inverted papillomas throughout the upper collecting system have been seen to have a smooth, rounded surface [26]. There may be an impression of an intact epithelial layer in the appearance. These differences have not been prominent enough to allow visual identification, but they have been strongly suggestive. All benign lesions observed, including fibroepithelial polyps, inverted papillomas, and hemangiomas located in the ureter or the ureteropelvic junction can be narrow, elongated, and worm‐like.

In many instances, visual inspection alone may not be adequate for diagnosis. High‐grade UTUC can be confused with inflammatory lesions or may be obscured by tumor growing submucosally or proximal to obstructive edema. There may be calculus material on the surface of a neoplasm with the resultant appearance of a solid calculus. Other tumors with a necrotic surface can appear the same as a soft, infection stone covered with inflammatory debris. In these and many other situations, visual inspection alone is not adequate for diagnosis.

Aids to visual diagnosis of neoplasms such as narrow‐band imaging (NBI) and confocal laser endomicroscopy have been used in the bladder to detect carcinoma in situ or additional exophytic tumors. NBI is an optical image‐enhancement system that makes use of blue and green wavelengths of light, which are readily absorbed by hemoglobin to enhance surface tumor detection by providing contrast between normal mucosa and microvasculature. Since malignant lesions tend to have a rich vascular component, they appear dark brown or green against white mucosa thus enhancing lesion detection. One report of NBI for use in cases of UTUC found a 23% improved detection rate among 27 patients in which additional tumors were seen or borders of tumors were enhanced and noted to extend beyond what was observed with white light alone [27]. NBI also has value in differentiating benign inflammation, as seen from indwelling stents, from subtle malignant luminal lesions [28]. Unlike photodynamic diagnosis modalities, NBI requires no extrinsic fluorochrome, an attractive aspect for use in the upper tracts.

Endoscopic biopsy technique

Ureteroscopic biopsy is necessary to sample neoplasms in the upper urinary tract to determine the presence of malignancy, and to determine the grade. The rate‐limiting step of ureteroscopic biopsy is the size of the working channel within the ureteroscope, which dictates the size of the biopsy instrument that can be used. For example, a piece of tissue obtained with a 3 Fr cup biopsy forceps is less than 1 mm in diameter and is usually too small to be prepared for histologic study using standard techniques. It is often lost in the process (see Video 50.1a). In contrast, it is a relatively large fragment of tissue for cytologic techniques. It can be prepared as a cell block and stained and examined as a histologic preparation to give a diagnosis and possibly grade.

Several different biopsy instruments and techniques are available. Abdel‐Razzak and colleagues [29] evaluated samples from 55 procedures in 44 patients with a possible diagnosis of UTUC. They compared the diagnostic yield, considering only those samples that were specifically positive or negative for malignancy, excluding those that were “suggestive” or equivocal. The techniques compared aspiration of urine at the level of the lesion, wash and aspiration with saline solution at the area of the lesion, and direct tissue sampling with brush, basket, or biopsy forceps.

The tissue sampling techniques gave the best yield, particularly the flat wire basket for large friable tumors and the cup forceps for more sessile lesions. The brush was less effective, and under endoscopic vision was observed to move the more flexible tissue without removing fragments. It may be more useful with flat or sessile lesions. Aspiration and wash proved to be valuable in providing a diagnosis for some patients in whom the other sampling techniques were inconclusive.

A flat wire basket is quite effective for removing large fragments of papillary tissue with a small‐diameter ureteroscope (see Videos 50.2a–c and 50.6 ). We highly recommend this instrument for biopsy of UTUC whenever applicable since it has been shown to be superior to the 3 Fr cup biopsy forceps in securing a diagnosis of UTUC in suspected lesions [30]. Under endoscopic vision, the basket is placed on the tumor and partially closed. The entire unit consisting of tumor sample, basket, and ureteroscope is then removed from the ureter and bladder. This can often remove a large sample even up to 1 cm in diameter, which is adequate for cytologic or histologic study. The ureteroscope is then replaced to repeat the inspection and biopsy or treat the neoplastic lesion.

The most important steps in handling the tissue for pathologic diagnosis is to work closely with the cytopathologist [31–34]. Samples are examined with both a smear and cytospin preparation. If there is any macroscopically visible tissue in the sample, a cell block is also prepared. This sample often demonstrates both the architecture of the neoplasm and the individual cells to allow grading of UTUC in many of the samples adequate for cell block. Multiple samples of the lesion are taken. In addition, urine and saline wash samples of the lesion before and after biopsy and/or treatment are also obtained (Box 50.1).

Grading with ureteroscopy

Grading of UTUC is important in determining prognosis and directing therapy. Grade obtained from ureteroscopic biopsy has been shown to reflect the grade of the overall tumor with reasonable accuracy. In 42 patients, Keeley and colleagues [35] found that the grade seen on a ureteroscopic biopsy prior to surgical treatment matched that in the final pathologic specimen in 38/42 (90%) of cases. Daneshmand and colleagues [36] showed an overall accuracy of 90% in patients who had surgery early after biopsy and in those who had surgery within 2 months of ureteroscopic diagnosis. In a larger, more recent series, Brown et al. demonstrated ureteroscopic grading accuracy in 112/119 (94%) of patients [37]. Other groups, however, have expressed concern over grade discordance between ureteroscopic and surgical specimens such that 23/24 (96%) of grade 1 lesions and 23/57 (40%) of grade 2 lesions were upgraded [38]. This exceptional finding is likely explained by the use of multiple grading systems for urothelial carcinoma used over the years, which are not simply interchangeable. In the surgical pathology literature, grade 2 UTUC lesions as defined by the 1973 World Health Organization (WHO) classification have demonstrated significant heterogeneity such that up to 50% of them would qualify as high‐grade lesions according to the 1998 WHO system [39, 40]. This is very important to consider whenever interpreting studies involving the ureteroscopic treatment of UTUC over time since most studies are retrospective single institutional experiences taking place over many years in which the grading systems had changed. To consider all 1998 “low‐grade” UTUCs as 1973 grade 1 cases would certainly explain the high rate of grade 1 upgrading to grade 2 in the 2012 Mayo series. Nevertheless, the possibility of UTUC tumors being heterogeneic in regard to grade must be considered, especially in view of the findings with urothelial carcinoma of the bladder in which up to 29% of primarily low‐grade non‐muscle invasive tumors had a high‐grade component of at least 5% tumor volume [41]. The heterogeneity of grade 2 lesions also explains the benefit of combining site‐specific cytology with ureteroscopic biopsy in patients with grade 2 UTUC to provide a more accurate diagnosis [42].

Staging

Pathological stage has been shown to be the best predictor of prognosis in patients undergoing treatment for UTUC [43, 44]. Many factors are responsible for unreliable UTUC staging with ureteroscopic biopsy techniques including small specimen size due to limits of instrument size, relative thinness of the ureteral wall which could lead to extravasation with aggressive biopsy and the variable morphologies of the intrarenal collecting system resulting in “hard‐to‐reach” lesions. It is impossible to expect reliably complete excisional biopsies in the upper tract. Contemporary series report stage concordance rates of only 49–68% with the overwhelming trend demonstrating understaging of ureteroscopic biopsies [42, 45, 46]. Reliably determining the depth of invasion of the primary tumor or other simultaneous lesions remains difficult. One series advocated multiple deep biopsies with cup forceps in an attempt to determine the presence of tumor in the lamina propria [47]. Most series have not reported accuracy in determining the depth of invasion.

The grade of the primary tumor has often been associated with stage, but it cannot be considered truly accurate staging. In Keeley’s series [35], increasing stage was noted with increasing grade seen on ureteroscopic biopsy. Brown and colleagues also found that the grade on endoscopic biopsy correlated with the final pathologic stage in nephroureterectomy specimens [37]. Findings from these two studies demonstrated that low‐grade UTUC on ureteroscopic biopsy correlated with noninvasive stage (<pT1) in 73–86% and that high‐grade UTUC on biopsy results in more invasive cases (>pT2) in 66%. Other series of patients treated surgically have also demonstrated the relationship of increasing stage with increasing grade [48].

Cross‐sectional imaging is essential for determining the presence of overtly metastatic disease but historically has not been very accurate in predicting subtly invasive disease (pT2–pT3). Favaretto et al. recently presented a model which combines ureteroscopic biopsy results with cross‐sectional imaging and predicts > pT2 disease with an accuracy of 71% [49]. Endoluminal ultrasound has been used in two series in an attempt to determine the depth of invasion [50, 51]. It has shown some value but is severely limited by the availability of the instruments.

Optical coherence tomography (OCT) is a new technological advancement that makes use of backscattered light to produce micrometer‐level resolution cross‐sectional images such that layered tissue anatomy can be appreciated. A 2.7 Fr probe can be placed through the lumen of a flexible or semirigid ureteroscope at the level of a urothelial lesion for cross‐sectional imaging. Depth of imaging is reported at 2 mm and OCT staging is binary such that invasive disease is classified as > pT1. An early validation study compared OCT stage to surgical stage after RNU and demonstrated 100% concordance in seven cases using the binary classification [52]. One case could not be staged due to tumor thickness going beyond OCT imaging depth. More experience is needed before the utility of this modality is fully appreciated.

Complications of biopsy

There remains some concern that ureteroscopic biopsy of UTUC can disseminate tumor cells locally or systemically. The possibility of pyelovenous or pyelolymphatic backflow has been cited as a possible mechanism. In a single case report, tumor cells were found outside the kidney in a nephroureterectomy specimen after ureteroscopic biopsy [53]. However, in a review of 13 nephroureterectomy specimens following ureteroscopic biopsy, no unusual metastatic pattern was seen [54]. In a well‐controlled study of 96 patients, Hendin and colleagues [55] found no difference in long term or disease specific survival in patients with UTUC who had surgical treatment preceded either with or without ureteroscopic biopsy (Table 50.1). Hara and colleagues [56] reported the usefulness of ureteroscopic biopsy and added 50 patients to those who have had ureteroscopic biopsy without development of metastatic disease. These series have concluded that ureteroscopic biopsy can be a safe and very valuable procedure without any documented evidence of tumor dissemination.

Selection of patients for ureteroscopic biopsy

Ureteroscopic biopsy is of value in any patient with an upper tract filling defect in whom the diagnosis is in question, such as those with a filling defect and voided urinary cytology without a definitive (positive) diagnosis for malignant cells. The presence of individually malignant‐appearing cells (positive cytology) indicates either carcinoma in situ or a high‐grade neoplasm. Biopsy may be avoided in patients with cytology that is definitively positive for malignant cells and who have a large irregular upper tract filling defects, which can be considered classic for UTUC. Even these patients should have endoscopy to rule out associated bladder tumor.

Natural history and prognosis after extirpative surgery

The rationale for conservative endoscopic therapy of UTUC was based initially on the success of other conservative treatment modalities and the natural history of this neoplasm. The behavior and prognosis of UTUC, in both the ureter and the intrarenal collecting system, has repeatedly been shown to be related to the grade and stage of the lesion. In many early, published series of extirpative surgery for UTUC, the vast majority of cancer‐related deaths were in those with high‐grade disease, in whom muscle invasion was also frequently present. Survival of 49 patients with Grade I UTUC of the ureter or renal pelvis collected at the Mayo Clinic over a 22 year period was identical to that of an age‐matched control group [57]. In contrast, the survival with higher‐grade UTUC correlated with tumor stage and grade and was consistently lower than a control group [58]. Lymph node‐positive disease also was dependent on tumor grade. In a series by Charbit and colleagues [48], lymphadenectomy was negative in all patients with low‐grade tumors in whom it was performed while 39% of those in patients with higher‐grade tumors were positive.

Endoscopic therapy

Endoscopic therapy in the upper tracts for UTUC treatment is a natural extension of the well‐accepted techniques for treating lesions in the bladder, only with smaller instruments imparting some unique limitations. The neoplasm itself, including its diagnosis, grade, location, and size, must be considered in any decision for endoscopic treatment in an individual patient (Table 50.2). There are several ureteroscopic techniques for the treatment of UTUC and they include mechanical removal, electrosurgical resection, fulguration, and laser therapy.

Tumor factor	For	Against
Size	Small	Large
Configuration	Papillary	Sessile
Number	Solitary	Multiple
Distribution	Single	Circumferential or extensive
Grade	Low	High
Cytology	Negative	Positive

The techniques used for the ureteroscopic biopsy of tumors result in the removal of tissue volume. A flat wire basket can remove several millimeters of papillary tumor with each application (see Video 50.6). Although the cup biopsy forceps removes a small volume with each bite, repetitive sampling can remove a small tumor (see Video 50.1a). The base of the tumor can then be coagulated with one of the other instruments (see Video 50.1b). Electrosurgical techniques similar to those used in the bladder have been applied for small distal ureteral neoplasms using longer, small‐diameter endoscopes. Over time, this tedious procedure has been superseded by other more efficient techniques.

Ureteroscopic electrocoagulation of UTUC is possible using 2 or 3 Fr probes which can be passed through the channels of small‐diameter rigid or flexible ureteroscopes. Care should be maintained to avoid fulgurating large areas of the ureter, which can result in stricture formation. This electrocautery technique is also useful for lesions within the intrarenal collecting system often in the lower pole medially where laser fibers may limit deflection of the ureteroscope. The 2 Fr electrode is slightly more flexible and can fulgurate with lateral contact rather than directly forward approach needed for a laser (see Video 50.5b ).

Laser techniques have been applied safely and efficiently for UTUC treatment. Small fibers of 200–400 µm core diameter can be passed through the flexible ureteroscope. The two most commonly utilized lasers presently available can effectively treat UTUC with coagulation, ablation and resection. The neodymium:YAG laser was first used for treatment of bladder tumors and for renal pelvic and ureteral neoplasms in open surgical procedures achieving long‐term cures [59]. It was subsequently used ureteroscopically to ablate urothelial carcinoma of the ureter [60]. In a comparative series, Schmeller and Hofstetter [61] demonstrated the success of laser ablation of upper tract tumors with the development of fewer ureteral strictures than after electrocoagulation.

The neodymium:YAG laser can penetrate up to 5 mm into tissue after several seconds of exposure. This can be controlled by positioning the fiber onto the tumor without directly aiming it toward the wall of the ureter and by moving the fiber across the surface of the tissue to avoid prolonged exposure. Ureteral damage may be limited by aiming the fiber and the beam parallel to the surface of the ureter. Within the kidney, especially the renal pelvis, where there is a greater surface area and less risk of scarring and stricturing, the neoplasm can be coagulated safely with the neodymium:YAG laser [62] (see Video 50.3). The laser is activated at 20–30 W on continuous mode and moved over the surface to coagulate the tissue. The effect can be seen as the color of the tissue changes to white. The laser fiber will char if it is activated in contact with tissue. For a relatively large lesion obstructing the ureter or an infundibulum, it may be necessary to remove some of the coagulated tissue with a basket or grasper to determine whether viable tumor remains. Since the laser can penetrate to a depth of approximately 5 mm, it may not affect the entire depth of the tumor. There have been no reports of significant renal or vascular injury or damage to associated organs from forward scatter of the neodymium:YAG laser that has been used in the renal pelvis.

The holmium:YAG laser has been widely applied for urologic indications. It is a solid‐state pulsed laser that can fragment calculi and can coagulate and ablate tissue. This laser produces light at a wavelength of 2100 nm carried along a low‐water‐content fiber. The laser energy is absorbed within less than 0.5 mm of tissue or fluid and has essentially no risk of forward scatter. The effect observed is the only tissue effect achieved. It is particularly useful for ureteral lesions since it can ablate and remove a visually occlusive neoplasm to open the lumen for access [63–65] (see Video 50.4 ).

In use, the laser fiber must be placed in contact with or very close to the tissue to be treated. The laser is then activated at energies from 0.5 to 1 J at a frequency of 6–10 or even 15 Hz. Irrigation is maintained to clear the visual field of tissue debris. It is often necessary to discontinue treatment to allow the field to clear, since considerable debris is formed during treatment. Bleeding occurs occasionally and can be controlled better at lower energies or by moving the fiber slightly away from the tissue to diffuse the laser beam and improve coagulation. There is also clinical evidence that using longer pulse duration such as 700 microseconds, rather than the 350 microseconds often used for lithotripsy, will also improve coagulation (see Video 50.5a). The very limited penetration allows precise control and the laser, thus, can be used for ureteral lesions located at the level of the iliac vessels and the renal pelvis near the renal vessels. Great care is employed to avoid ablation and resection through the wall of the ureter or renal pelvis itself.

These lasers are best used in synergistic combination. The effects of the neodymium:YAG and holmium:YAG lasers are complimentary. The neodymium:YAG laser can be used to coagulate the major volume of tumor since it penetrates several millimeters and can achieve coagulation effect within the depth of the tissue. The coagulated tissue can then be removed mechanically or even more effectively with the holmium:YAG laser. The holmium:YAG is used to resect the tissue to the level of the wall of the ureter or renal pelvis. Thus, the benefits of each device can be used to the best advantage (Figure 50.1).

Results of treatment

Ureteroscopic treatment of UTUC has been employed and studied for well over 30 years. There are many small retrospective series with variable tumor characteristics treated with non‐uniform techniques and follow‐up protocols. These are reported with various endpoints such as cancer‐specific survival (CSS), local recurrence rates in the upper tract and bladder, renal preservation rate, and progression of disease defined in many different ways. Reports of metastatic disease are not uniformly presented, likely representing underreporting. Cohorts describing short‐ to intermediate‐term results are plentiful while larger series with longer follow‐up approaching 5 years have been published more recently. The indications for ureteroscopic treatment of UTUC have expanded from small low‐grade lesions in patients with imperative indications to medium‐ and larger‐sized lesions in patients with normal contralateral kidneys. Generally, recurrence rates become higher with longer follow‐up, and treatment of larger, and high‐grade, lesions. Non‐malignant ureteral strictures are not uncommon as a result of repetitive manipulations over time.

Recurrences

UTUC recurs at significant rates similar to locally treated bladder tumors. It is impossible to determine whether these new neoplasms are the result of implantation of cells from the original tumor or if it is related to a field change in the urothelium. Successful treatment depends on several factors A meta‐analysis by Cutress et al. summarize the local recurrence rates and CSS of 20 contemporary ureteroscopic series in the treatment of UTUC [66]. Clearly, this is influenced by the grade of the original lesion with rates between 48 and 54% for low‐ to intermediate‐grade lesions and as high as 60–76% for high‐grade lesions. The grade of the original lesion also affects CSS with most series reporting rates of 86–100% with mean follow‐up of 5 years or less (Table 50.3). Equally important are the length of follow‐up and the size of lesions being treated. These factors vary widely from series to series but in general, local recurrence rates increase with longer follow‐up and larger sized lesions. When considering the more recent series in Table 50.3, local recurrence rates of 77–90% are seen with series of more than 48 months follow‐up [75, 77–79]. An exception to this trend was noted in the 2008 Mayo series with a 55% local recurrence rate with 59 month follow‐up but the average lesion size treated in this series was only 8 mm [74]. In general, these recurrent lesions are small and can be treated endoscopically. A notable exception is when there is progression in grade from low‐ to a newly developed high‐grade lesion. The rate of such grade progression has been defined by Grasso et al. as 15% at a mean of 38.5 months. This should be mentioned to patients considering ureteroscopic treatment for UTUC during initial consultation [78].