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Upper Tract Urothelial Cancer


Upper urinary tract urothelial carcinoma, or UTUC, refers to cancers of the renal calyces, renal pelvis or ureter. The renal calyces, renal pelvis and ureter are responsible for transporting urine from the kidney to the bladder

Alternate names

Transitional Cell Carcinoma of the Kidney; Urothelial Cancer of the Kidney

Causes, incidence and risk factors

UTUCs are relatively uncommon and account for only 5 percent to 10 percent of urinary tract cancers. These cancers develop primarily in people older than 70. Men are affected twice as frequently as women.
  • Smoking: Smoking is one of the largest adjustable risk factors for developing UTUC. The risk increases with both the amount and duration of smoking and appears to decrease over time with smoking cessation.
  • History of bladder cancer: Patients with a history of bladder cancer are at increased risk of developing UTUC.
  • Chronic inflammation: Chronic inflammation from recurrent urinary tract infections or kidney stones can increase the risk of developing UTUC.
  • Analgesics: Abuse of phenacetin (no longer available) is associated with an increased risk of developing UTUC.
  • Chemotherapy: Exposure to cyclophosphamide or ifosfamide appears to increase the risk of developing UTUC.
  • Occupation: Exposure to aromatic amines in the chemical, petroleum and plastic industries increases the risk of developing UTUC.
  • Genetics: Hereditary UTUC can be found as part of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma, or HNPCC). People with this syndrome are at risk for colonic, urothelial, gastric, pancreatic, uterine, sebaceous and ovarian carcinomas. People with Lynch syndrome who develop UTUC tend to present at a younger age (50s) compared with those who develop the non-hereditary form. If this form is suspected, it will be important to discuss genetic testing with your physician.
  • Aristolochic acid nephropathy: Aristolochic acid is a toxin produced by the aristolochia plant and consumption can lead to an increased risk of renal damage and UTUC in people with a specific genetic mutation. Aristolochic acid is used as a medicinal Chinese herb (Chinese herb nephropathy) and has been found as a contaminant in wheat from the Balkan region (Balkan nephropathy).

Signs and symptoms

The most common presenting symptom of UTUC is blood in the urine (hematuria). It occurs in approximately 75 percent of patients. This can be blood that you see (gross hematuria) or blood that is seen only on a urine dipstick or microscopy (microscopic hematuria). Flank pain is the second-most-common presenting symptom and is usually the result of the tumor obstructing the flow of urine from the kidney. It occurs in approximately 30 percent of patients. Additional urinary symptoms that may be present include increased frequency, urgency and pain with urination. Other possible symptoms, often indicating more advance disease, include fatigue, unintentional weight loss, low red blood cell count and bone pain.

Tests, treatments

If UTUC is suspected by your physician after a full history and physical exam, several additional tests and/or procedures may be performed to help make the diagnosis and appropriately stage your cancer if detected.

Urine studies

  • Urinalysis may show blood in the urine.
  • Urine cytology (microscopic examination of cells in the urine) may reveal cancer cells.

Blood tests

  • A complete blood count may be obtained to look for evidence of anemia.
  • A metabolic panel may be obtained to check your kidney function.
  • A hepatic panel may be obtained to check your liver function.

Imaging studies

  • CT urography or MRI urography is radiologic examination of the abdomen and pelvis that looks for causes of blood in the urine. In the case of UTUC, the test is looking for areas of the urinary tract that are not visualized which may be the result of a tumor being present.
  • In patients who cannot undergo CT or MRI with contrast, a renal ultrasound or non-contrast CT combined with cystoscopy and retrograde pyelograms may be performed instead.
  • In patients who there is a concern for metastatic disease, additional imaging such as a chest X-ray or bone scan may be obtained.


  • Cystoscopy: Evaluation of the bladder with a small camera either in the office or in the operating room is performed to rule out the presence of bladder cancer since it is associated with UTUC .
  • Ureteroscopy with biopsy: An evaluation of the upper urinary tract in the operating room that allows direct visualization of the urinary tract along with biopsy and possibly treatment of any suspicious lesions.


After a diagnosis of UTUC has been made, the urologist will have a discussion with you regarding your best treatment options. Treatment options take into account the grade of the cancer (a measure of the aggressiveness), stage of the cancer (is it confined to the urinary tract or is there evidence that is has spread to other locations), location of the cancer (renal pelvis only, ureter only, whether or not there is bladder involvement), patient comorbidities, including baseline kidney function, as well as patient preferences. Treatment options based on location are reviewed below.

General Guidelines

  • The primary treatment for UTUC that has not spread outside of the urinary tract is usually surgery.
  • Open, minimally invasive (laparoscopic or robotic) and endoscopic surgical options are available at the University of Florida.
  • Some patients are offered chemotherapy before surgery, while others are offered chemotherapy after surgery based on the final pathology.
  • If metastatic disease is present at diagnosis, it is usually treated with chemotherapy.

Renal Pelvis Tumors

  • Low-grade tumors may be managed by surgical removal of the kidney, ureter, and a small portion of bladder (nephroureterectomy) or by a kidney-sparing procedure where tumors are treated via ureteroscopy or through a percutaneous procedure done through the back.
  • High-grade tumors or large low-grade tumors are managed with a nephroureterectomy and regional lymph node dissection.

Ureteral Tumors

  • The specific surgical procedure offered often depends on the location of the tumor within the ureter (proximal versus mid versus distal ureter).
  • Proximal ureteral tumors are those that are close to the renal pelvis. These tumors are most commonly treated with a nephroureterectomy plus regional lymph node dissection for high-grade tumors. Some low-grade tumors can be managed with a kidney-sparing approach using ureteroscopy to treat the tumor.
  • Mid ureteral tumors are those located halfway between the kidney and the bladder. Large, high-grade lesions are usually treated with nephroureterectomy and regional lymph node dissection. Kidney-sparing procedures including ureteroscopy as well as removal of just part of the ureter and a reconstruction are possible in certain situations.
  • Distal ureteral tumors are those that are close to the bladder. The preferred treatment is removal of the distal ureter with reimplantation of the ureter into the bladder (distal ureterectomy) plus regional lymph node dissection for high-grade tumors. Occasionally a nephroureterectomy is required. A kidney-sparing approach using ureteroscopy to treat the tumor is also an option for some tumors.

Expectations (prognosis)

After UTUC is treated surgically with or without chemotherapy you will be closely monitored over time for disease recurrence and/or progression. This usually consists of periodic imaging of the upper urinary tracts. Additionally, serial cystoscopies are performed to make sure that bladder cancer does not develop since the two cancers are closely associated with each other.


  • NCCN Guidelines Version 1.2017 Bladder Cancer
  • Campbell-Walsh Urology, Eleventh Addition. Chapter 58: Urothelial Tumors of the Upper Urinary Tract and Ureter.

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