Ureteric Cancer

Ureteric cancer is a rare type of cancer that develops in the ureters, the tubes that carry urine from the kidneys to the bladder. Though uncommon, it most often affects older adults and is closely linked to bladder cancer, requiring careful monitoring and specialized treatment.

Table of contents

• What is Ureteric Cancer
• The Ureters and Urinary System
• Types of Ureteric Cancer
• Risk Factors and Causes
• Signs and Symptoms
• Diagnosis
• Treatment Options
• Prognosis and Staging
• Relationship with Bladder Cancer

What is Ureteric Cancer

Ureteric cancer, also called ureteral cancer, is a growth of abnormal cells that starts in the ureters^[1]. The ureters are tubes that connect the kidneys to the bladder, forming part of the urinary tract. They carry urine produced by the kidneys to the bladder for storage^[1].

This type of cancer is not common. When it does occur, it happens most often in older adults and in people who have had bladder cancer^[1]. Although cancer of the ureter and renal pelvis (the hollow part at the center of each kidney) is rare, when it does occur it affects mainly men, and usually people over the age of 65^[3].

• Ureters
• Kidneys
• Renal pelvis
• Bladder

The Ureters and Urinary System

The urinary system removes waste from the body through urine. The kidneys sit toward the back of the upper abdomen. They filter waste and fluid from the blood and make urine^[1]. Each kidney is about 5 inches long and 3 inches wide and shaped like a kidney bean^[8].

Urine moves from the kidneys to the bladder through narrow tubes called the ureters. Each ureter is about 25 to 30 cm (10 to 12 inches) long^[4]. The bladder stores urine until it’s time to urinate. Urine leaves the body through a small tube called the urethra^[1].

The walls of each ureter are made up of three main layers of tissue. The urothelium (also called transitional epithelium) is the inner lining of each ureter. It is made up of special cells called urothelial cells or transitional cells, which can stretch and change shape as urine flows^[4]. The lamina propria is a thin layer of connective tissue that surrounds the urothelium and contains blood vessels, nerves and glands. The muscularis propria is a thick, outer muscle layer that pushes urine from the kidney down to the bladder^[4].

Types of Ureteric Cancer

Most upper tract cancers are of transitional cell type. The cells that line the ureters are the same type of cells that line the inside of the bladder^[1]. Cancer that starts in these cells is called urothelial carcinoma (also called transitional cell carcinoma). It makes up about 90% of all upper urinary tract tumors^[4].

Ureter and renal pelvic cancer most often originate in transitional cells, which are cells in the lining of the bladder^[3]. Between 5% and 10% of all urothelial cancers start in the ureter or renal pelvis and are diagnosed as upper tract urothelial carcinoma (UTUC)^[2].

A small percentage of ureter cancers, approximately 10 percent, start in the squamous cells, flat cells in the outer layer of the skin, that line the respiratory and digestive tracts, and hollow organs^[3]. Other rare types of cancers that can develop in this area include adenocarcinoma, sarcoma and melanoma^[9].

Risk Factors and Causes

Although the cause of ureter cancer is unknown, several factors may increase your risk of developing this disease^[3]. Smoking most likely increases risks, as does exposure to a variety of chemicals and dyes found in factories that make leather goods, textiles, plastics, and rubbers^[3].

Having a personal history of bladder cancer is an important risk factor. A previous history of bladder cancer increases risk^[3]. People diagnosed with ureteral cancer have an increased risk of bladder cancer^[1].

Other risk factors include:

• Being age 60 or older^[9]
• Taking certain pain medicines, such as phenacetin^[7]
• Exposure to excessive radiation^[2]
• Having frequent urinary tract infections^[9]
• Having human papillomavirus (HPV)^[9]

Patients with a syndrome called Lynch Syndrome also have an increased chance of developing upper tract urothelial carcinoma. Lynch Syndrome is an inherited cancer syndrome. An estimated 21% of patients with upper tract urothelial carcinoma have a variant of Lynch Syndrome^[2].

Signs and Symptoms

Signs and symptoms of ureteral cancer can vary. Some symptoms can appear in the early stages of ureteral cancer, but may also appear as the tumor grows^[7].

Symptoms for cancer of the ureter include:

• Blood in the urine (may be microscopic, found using a urine test)^[2]
• Back pain or pain at the juncture of ribs and spine^[3]
• Flank pain (the right or left side of the lower torso)^[2]
• Painful or frequent urination^[7]
• Weight loss (unintentional)^[3]
• Extreme fatigue^[7]
• Urinary tract infections^[2]

While these symptoms can be unrelated to ureteral cancer, be sure to check with your doctor to make sure they are addressed^[7].

Diagnosis

To diagnose ureteral cancer, a healthcare professional might start by asking about your symptoms and examining your body^[5]. A mass or an enlarged kidney cannot be detected by examining the abdomen by touch^[3].

A combination of tests help a physician make a diagnosis:

Imaging tests make pictures of the body. They may help your healthcare team better understand the size of the cancer. Imaging tests also can look for signs that cancer may have spread beyond the ureter^[5]. These include:

• Intravenous pyelogram (IVP)^[3]
• Computerized tomography urogram (CT urogram)^[5]
• Magnetic resonance urogram (MR urogram)^[5]
• Abdominal CT scan^[3]
• Kidney ultrasound^[3]
• Positron emission tomography scan (PET scan)^[5]

Urine tests may include a urinalysis to analyze your urine. A urine cytology test may be used to look for concerning cells in a urine sample^[5].

Ureteroscopy involves inserting a thin, lighted tube equipped with a camera into the urethra. The device is passed through the bladder and into the ureters. This makes it possible for a healthcare professional to inspect the ureters. If necessary, a biopsy is taken during the procedure. A biopsy is a procedure to remove a sample of tissue for testing in a lab^[5].

Information from these procedures is used to assign a stage to cancer. The stage tells your healthcare team about the extent of the cancer and about your prognosis^[5].

Treatment Options

Surgery is the main treatment for cancer of the renal pelvis or ureter^[12]. The criteria for deciding on a course of treatment includes the patient’s age and overall health, in addition to the type of tumor, its grade, stage and position^[3].

Surgical Options

Radical nephroureterectomy is the most common surgery done for cancer of the renal pelvis or ureter. The surgeon removes the entire kidney, all of the ureter and the tissue where the ureter connects to the bladder (called the bladder cuff). The surgeon may also remove some nearby lymph nodes and surrounding tissue^[12]. This is done using a general anesthetic (you will be unconscious). The surgeon most often does laparoscopic surgery, which involves making several small cuts and using special tools^[12].

Segmental resection of the ureter is usually only done to remove small tumors in the lower part of the ureter closest to the bladder. The surgeon removes the part of the ureter with the tumor in it along with a margin of healthy tissue above the tumor. Then the ureter is reattached to the bladder^[12]. If the tumor is small and localized, it is possible to remove only the part of the ureter that contains cancer cells^[3].

Endoscopic surgery may be done for cancer of the renal pelvis or ureter that is low grade and at an early stage. It may also be done when the kidneys aren’t working well, you only have one kidney or there is cancer in both sides of the urinary tract^[12]. The surgeon removes the tumor using an endoscope and cutting tools passed through the endoscope. A laser deployed at the end of the tube may be used to destroy the tumor^[6].

Chemotherapy

Chemotherapy uses anticancer drugs to destroy cancer cells. It can be used before surgery (neoadjuvant chemotherapy) or after surgery (adjuvant chemotherapy) to treat cancer of the renal pelvis or ureter that has spread to the lymph nodes or other parts of the body^[12].

Systemic chemotherapy has an established role in patients with metastatic disease. A combination of drugs can reduce the chance of the cancer recurring after surgery^[16]. Patients with ureter cancer in a higher risk category who have undergone surgery can benefit from drug therapy^[16].

Topical chemotherapeutic agents can be delivered by instillation. Bacillus Calmette-Guérin (BCG), which is the preferred agent, or mitomycin C can be administered either percutaneously or via a retrograde approach through a ureteral catheter^[16]. In 2020, mitomycin pyelocalyceal was approved for treatment of low-grade upper tract urothelial cancer in adults and is instilled via ureteral catheter or a nephrostomy tube^[16].

Radiation Therapy

Some patients with ureter cancer benefit from radiation to the area of the tumor. This is usually done in combination with surgery and chemotherapy^[14].

Immunotherapy

Immunotherapy is used for second-line treatment of metastatic upper tract urothelial cancer. Intravenous immunotherapy using a drug called nivolumab is now approved for certain patients following surgery who are not eligible for chemotherapy^[7].

Prognosis and Staging

The stages of ureter cancer are determined by the size of the malignancy and whether or not the cancer cells have spread past the ureter or renal pelvis. Localized cancer remains at the point of origin, and has not spread beyond the kidney or ureter. Regional cancer has progressed into the tissue surrounding the kidney and/or neighboring lymph nodes, while metastatic cancer has invaded other parts of the body^[3].

The major prognostic factor at the time of diagnosis of upper tract transitional cell cancer is the depth of infiltration into or through the wall. Most superficial tumors are likely to be well differentiated, while infiltrative tumors are likely to be poorly differentiated^[19].

How deep the tumor has grown into the wall of the renal pelvis or ureter is an important prognostic factor. The deeper the tumour has grown into the wall, the less favourable the prognosis^[24]. Low-grade cancers of the renal pelvis or ureter do not usually grow into the muscle layer and do not usually spread to other parts of the body. Because of this, low-grade cancers tend to have a good prognosis. High-grade cancers have a greater risk of spreading and a poorer prognosis^[24].

Transitional cell cancer of the renal pelvis and ureter is curable in more than 90% of patients if they are superficial and confined to the renal pelvis or ureter. Patients with deeply invasive tumors that are confined to the renal pelvis or ureter have a 10% to 15% likelihood of cure. Patients with tumors with penetration through the wall or with distant metastases usually cannot be cured with available forms of treatment^[19].

Relationship with Bladder Cancer

Ureteral cancer is closely related to bladder cancer. The cells that line the ureters are the same type of cells that line the inside of the bladder^[1]. People diagnosed with ureteral cancer have an increased risk of bladder cancer. So people with ureteral cancer are usually tested for signs of bladder cancer^[1].

The incidence of subsequent bladder cancer after previous upper tract transitional cell cancer ranges from 30% to 50%^[19]. About 22-47% of the ureteral cancer cases will also develop bladder cancer at some time in the future^[2]. When involvement of the upper tract is diffuse (involving both the renal pelvis and ureter), the likelihood of subsequent bladder cancer increases to 75%^[19].

Additionally, 20-25% of patients with carcinoma in the bladder will develop upper tract urothelial carcinoma^[2]. Upper tract urothelial carcinoma in the renal pelvis or in the ureter can develop cancer in the bladder over time^[2].

Because of this close relationship, follow-up care is important. It’s common for bladder cancer to come back, even after successful treatment. As a result, it is important for people who have been treated for ureter cancer to visit their doctor regularly to get certain follow-up exams or tests^[26].