Urothelial Tumors of the Renal Pelvis and Ureters Workup

Updated: Jan 15, 2020
  • Author: Kyle A Richards, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Workup

Laboratory Studies

Laboratory studies that should be ordered include the following:

  • Urinalysis – To confirm hematuria and to rule out a coexistent urinary tract infection
  • Basic metabolic panel – To check serum creatinine (to assess renal function by permitting calculation of the glomerular filtration rate) and electrolytes
  • Liver function tests including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase
  • Complete blood count
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Imaging Studies

Excretory urography, commonly referred to as intravenous pyelography (IVP), has traditionally been used to evaluate the upper urothelial tract, but has been primarily replaced with multidetector computed tomography (CT). [13, 14] Approximately 50-75% of patients with urothelial tumors of the renal pelvis and ureters have a radiolucent filling defect that is characteristically irregular and in continuity with the wall of the collecting system. (See the image below.) Approximately 10-30% of such tumors cause obstruction or non-visualization of the collecting system.

Intravenous pyelogram (IVP) demonstrating an upper Intravenous pyelogram (IVP) demonstrating an upper calyx filling defect characteristic of upper tract urothelial carcinoma (UTUC). Blunting of the involved calyx is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.

Noncontrast CT scanning can be performed, followed by a contrast study, with particular interest in the excretory phase — a so-called CT urogram. Plain radiography, which demonstrates drainage and anatomy, can also be performed after CT scanning. Upper tract urothelial carcinomas (UTUCs) are usually visible as an irregular filling defect. They tend to be hypovascular in comparison with the rest of the kidney and demonstrate minimal increased attenuation (enhancement) following intravenous contrast injection. See the images below.

CT scan demonstrating right renal pelvis upper tra CT scan demonstrating right renal pelvis upper tract urothelial carcinoma (UTUC). Contrast in the renal pelvis is displaced by the tumor. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.
CT scan demonstrating left distal ureteral upper t CT scan demonstrating left distal ureteral upper tract urothelial carcinoma (UTUC). The left ureter is dilated and a medial filling defect is noted. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.

CT scanning sensitivities and specificities based on lesion size are as follows:

  • For lesions 5-10 mm in size - 96% sensitivity and 99% specificity
  • For lesions smaller than 5 mm in size - 89% sensitivity
  • For lesions smaller than 3 mm in size - 40% sensitivity

CT scanning has limited value in staging UTUC because stage Ta or superficial lesions cannot be differentiated from T2 or invasive lesions (see Staging). However, CT scanning is helpful in demonstrating peripelvic or periureteral tumor extension, thereby assisting with staging of aggressive disease. Hydronephrosis and obstruction are associated with a higher degree of invasiveness.

As with CT scanning, magnetic resonance imaging (MRI) is also of limited use in staging early UTUC; however, it may have greater utility in more advanced disease or in patients with limited renal function. European Association of Urology guidelines note that although CT urography is generally preferred to MRI urography for diagnosing and staging, MR urography is indicated in patients who cannot undergo CT urography, usually when radiation or iodinated contrast media are contraindicated. However, the use of MR urography with gadolinium-based contrast media should be limited in patients with severe renal impairment (creatinine clearance < 30 mL/min), due to the risk of nephrogenic systemic fibrosis. [1]

There is interest in fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT for staging in urothelial carcinoma, but, at present, this technique does not appear to have significant advantages over MRI. [15]

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Other Tests

Cytopathology of voided urine samples yields low sensitivity, especially for low-grade tumors, which results in normal cytology results in up to 80% of cases. The sensitivity of cytopathology increases for higher-grade tumors, which tend to shed more tumor cells. Cytology yields an accuracy of 83% in patients with high-grade disease. Cytology is less sensitive for UTUC than for bladder cancer.

Cytology samples should be taken from as near the suspected lesion as possible (eg, within the calyceal system if the tumor is suspected in that region). Positive cytology has been associated with more advanced (invasive) disease. [16] Selective washings of both the upper tracts and the bladder can aid in tumor localization. Cytology plays a role in urothelial tumor surveillance in conjunction with cystoscopy/ureteroscopy.

Fluorescence in situ hybridization (FISH) can be performed using probes for altered genes on chromosomes 3, 7, 17, and 9p21. FISH (UroVysion) is a useful test for detecting urinary tract cancer, as it yields a greater sensitivity for lower-grade tumors than cytology and other tests (as high as 76.6-100% vs 21-24% for cytology). [17, 18] Ureteral cancer has been detected with FISH during evaluation for hematuria. [19] FISH has equal specificity when compared with cytology (as high as 100%).

Flexible or rigid ureteroscopy can be used for direct visualization of a tumor. Important to note is that it can be used to obtain tissue (biopsy) for a diagnosis (histology) and grade in 90% of cases. [20] Staging information regarding depth of invasion, however, is more difficult to obtain.

 

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Diagnostic Procedures

Each of the following should be obtained in a suspected case of UTUC:

  • Cystoscopy – To rule out bladder tumor
  • Urinary cytology
  • CT urography

For cystoscopy, a small fiberoptic scope is inserted through the urethra in order to visualize the bladder. This ambulatory/clinical procedure is usually well tolerated by both women and men. A 16F flexible cystoscope is typically used. This procedure is mandatory to rule out coexistent bladder lesions, which occur with a frequency of 8-13%. [1] Cystoscopy is also essential for postoperative surveillance to monitor for bladder tumor development; bladder recurrence occurs in 15-51% of patients with UTUC. [21]

In retrograde urography (see image below), contrast is injected into the ureteral orifice with the aid of a cystoscope and a ureteral access catheter. This can be performed with fluoroscopic guidance or with standard radiography plates. Retrograde urography allows better visualization of the collecting system than excretory urography by increasing the distention of the urinary collecting system. Retrograde pyelography is preferable in patients with azotemia and/or contrast allergy. Overall, retrograde urography is more than 75% accurate in establishing a diagnosis of urothelial cancer.

Left retrograde ureterogram demonstrating the clas Left retrograde ureterogram demonstrating the classic "goblet" sign of ureteral upper tract urothelial carcinoma (UTUC). Ureteral dilation distally and proximally to the tumor is present. The narrowed wall of the ureter is irregular. Courtesy of Andrew J. Taylor, MD, University of Wisconsin Medical School.

Since the advent of rigid and flexible ureteroscopes, ureteropyeloscopy is used increasingly for the diagnosis of upper tract urothelial tumors. Biopsy forceps or cytology brushings can be used to collect tissue. This procedure yields an accuracy of 86% in diagnosing renal pelvis tumors and 90% in diagnosing ureteral tumors. Large size, broad base, and nonpapillary pattern favor tumor invasiveness. Studies have demonstrated that 85% of urothelial lesions in the renal pelvis are papillary papillary in morphology. The complication rate associated with ureteropyeloscopy is approximately 7%; these include perforation, complete disruption, and ureteral stricture.

Percutaneous nephroscopy is not indicated for the diagnosis of urothelial tumors of the renal pelvis and ureters because of the theoretical risk of tumor cell implantation in the retroperitoneum and nephrostomy tube tract. It is used for treatment in selected situations when nephron-sparing approaches are necessary.

Nevertheless, Huang et al concluded that percutaneous biopsy is safe and effective for diagnosis of upper tract urothelial lesions that are not amenable to endoscopic biopsy. In their study of 26 upper tract lesions in 24 patients, percutaneous biopsy provided tissue diagnosis in 85% of cases; the three recurrences in the nephrectomy bed developed at sites remote from the biopsy site and thus were not attributed to tract seeding. [22]

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Staging

The distribution of tumor stages and grades differs from study to study. Stage and grade yield the greatest prognostic value.

The National Comprehensive Cancer Network (NCCN) guidelines grade urothelial histologies according to the World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification, as follows [23] :

  • Low grade 
  • High grade 

Squamous cell carcinoma and adenocarcinoma use the following grading classifications [23] :

  • GX—Grade cannot be assessed
  • G1—Well differentiated
  • G2—Moderately differentiated
  • G3—Poorly differentiated 

Staging is based on the depth of tumor invasion and classified using the tumor, node, metastases (TNM) system. [24]  

Primary tumor categories are as follows:

  • TX - Primary tumor cannot be assessed
  • T0 - No evidence of primary tumor
  • Ta - Papillary noninvasive carcinoma
  • Tis - Carcinoma in situ
  • T1 - Subepithelial connective tissue invasion (lamina propria invasion)
  • T2 - Muscularis invasion
  • T3 – For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or the renal parenchyma
  • T3 - For ureter only - Tumor invades beyond muscularis into periureteric fat
  • T4 - Tumor invades adjacent organs, or through the kidney into the perinephric fat 

Regional lymph node categories are as follows:

  • NX - Regional lymph nodes cannot be assessed
  • N0 - Negative nodes
  • N1 - Metastasis ≤2 cm in greatest dimension in a single lymph node
  • N2 - Metastasis  > 2 cm in a single lymph node, or multiple lymph nodes

Distant metastasis categories are as follows:

  • M0 - No distant metastasis
  • M1 - Distant metastasis

The location of the tumor can affect the findings. Renal pelvis tumors are more commonly invasive than bladder tumors, possibly because of delayed diagnosis and a less well-developed muscle layer.

Table 1. American Joint Committee on Cancer Prognostic Groups (Open Table in a new window)

Stage

Tumor

Node

Metastasis

0a

Ta

N0

M0

0is

Tis

N0

M0

I

T1

N0

M0

II

T2

N0

M0

III

T3

N0

M0

IV

T4

NX, N0

M0

Any T

N1

M0

Any T

N2

M0

Any T

Any N

M1

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