Upper Tract Urothelial Carcinoma (UTUC) is a rare form of cancer that originates in the lining of the upper urinary tract. This lining, known as the urothelium, covers the renal pelvis—the part of the kidney that collects urine—and the ureters, which are the tubes that transport urine from the kidneys to the bladder. Approximately 7,000 new cases are diagnosed in the United States each year, making it a less common urinary tract cancer.
Understanding Upper Tract Urothelial Carcinoma
UTUC refers to malignancies that arise from the urothelial cells found in the renal calyces, renal pelvis, or ureters. While it shares similarities with bladder cancer, both being urothelial cancers, UTUC is distinct due to its anatomical location and less frequent occurrence. The urothelium in the ureter has a thinner muscular layer compared to the bladder, and in the renal pelvis, the urothelium can directly contact the kidney tissue. This anatomical difference influences how UTUC presents and is managed. UTUC accounts for about 5-10% of all urothelial malignancies.
Symptoms and Risk Factors
The most common symptom indicating UTUC is hematuria, which is the presence of blood in the urine, affecting approximately 75% of patients. This can be visible to the naked eye, known as gross hematuria, or only detectable under a microscope, referred to as microscopic hematuria. Other symptoms include flank pain, discomfort or pain in the side below the ribcage, occurring in about 30% of patients. This pain often results from the tumor obstructing urine flow from the kidney. Less common indicators, particularly in advanced cases, may include weight loss, loss of appetite, or night sweats.
Several factors increase the likelihood of developing UTUC. Smoking tobacco is considered the most significant risk factor, contributing to an estimated 25-60% of cases. The risk increases with the amount and duration of smoking, although it decreases over time after quitting. Exposure to certain chemicals, such as aromatic amines used in industries like chemical, petroleum, and plastic manufacturing, also elevates risk. Chronic kidney disease, recurrent urinary tract infections, and genetic predispositions like Lynch syndrome are additional risk factors. Individuals with Lynch syndrome, an inherited condition, tend to develop UTUC at a younger age, often in their 50s.
Diagnosis of UTUC
Diagnosing UTUC involves a combination of imaging studies, direct visualization, and cellular analysis. Computed tomography (CT) urography is often the preferred imaging method, providing detailed views of the urinary tract. Magnetic Resonance Imaging (MRI) urography is another option, offering similar diagnostic capabilities, particularly for patients who cannot undergo CT scans with contrast.
Ureteroscopy is a frequently used procedure for direct visualization and biopsy. During this procedure, a thin, lighted scope is inserted through the urethra and bladder, then advanced into the ureter and renal pelvis. This allows the urologist to directly see suspicious lesions and collect tissue samples for biopsy, which confirms the diagnosis and helps determine the tumor’s grade. While effective, obtaining a diagnostic biopsy can be challenging, with non-diagnostic rates ranging from 10-20%.
Urine cytology involves examining urine samples under a microscope to detect cancer cells. While it can be helpful, its sensitivity for detecting UTUC is lower compared to bladder cancer, with high false-negative rates between 50-90%. Despite this limitation, selective cytology from the affected upper tract has shown improved accuracy.
Treatment Options for UTUC
Surgical management is a primary approach. For high-risk or invasive UTUC, radical nephroureterectomy is the standard treatment. This involves the complete removal of the affected kidney, the entire ureter, and a small portion of the bladder where the ureter connects. Lymph nodes in the surrounding area may also be removed during this procedure.
For low-risk, smaller tumors, or in cases where preserving kidney function is a high priority, endoscopic management may be considered. This minimally invasive approach uses a ureteroscope to access and remove or ablate the tumor with a laser or electrocautery. Local recurrence rates after endoscopic treatment can be as high as 52-70%.
Systemic therapies, such as chemotherapy, are also employed. Chemotherapy drugs can be administered before surgery to shrink the tumor, or after surgery to reduce the risk of recurrence. For advanced disease, chemotherapy helps manage cancer spread. Immunotherapy, a newer treatment option, works by enhancing the body’s own immune system to target and fight cancer cells, particularly in advanced cases. Additionally, for low-grade UTUC, medications can be instilled directly into the kidney, ureter, or bladder.