About Upper Tract Urothelial Cancer

Upper tract urothelial carcinoma is a cancer that can occur anywhere from the inner linings of the kidney, down the ureter, in the bladder and down the urethra.

Typically 92% of all urothelial carcinomas occur in the bladder, but about 7-8% of urothelial carcinomas can occur in the upper lining of the kidney, which we call the calyx and renal pelvis. It could also occur in the ureter, or in the urethra. UTUC in the renal pelvis or in the ureter can develop cancer in the bladder over time.

Causes

Ureter Cancer Causes

Descending tumors are tumors that occur in the renal pelvis, or in the calyx, or in the ureters, and it actually feeds down into the bladder. And for those patients, we find that 22-47% of those patients will develop bladder cancer some time down in the future.

Causes:

  • Smoking
  • Analane dyes
  • Radiation
  • Genetics

Patients with a syndrome called Lynch Syndrome have an increased chance of developing upper tract urothelial carcinoma. Lynch Syndrome is an inherited cancer syndromes. UTUC is the third most common type of cancer of that syndrome, the most common being colon cancer.

We estimate that 21% of patients with upper tract urothelial carcinoma have a variant of Lynch Syndrome.

Signs and Symptoms

Symptoms of UTUC

  • Blood in the urine, which may be microscopic on a urine test
  • Urinary tract infections
  • Flank pain
  • Side and back pain
  • Kidney pain
Risk Factors

Risk Factors for Ureter Cancer

It is well known that tobacco increases risk for all types or urothelial carcinoma. Patients are two to three times at increased risk of developing urothelial carcinoma if they have exposure to analane dyes. Balkan endemic nephropathy, these are patients that are born or grew up in the Balkans, so Croatia, Bosnia Herzegovina, Romania, that have been exposed to a certain type of plant which is often used with wheat to make bread, but it’s European Birthwort, and increases their chance of not only renal failure, but increases their chance of actually getting upper tract urothelial carcinoma. This same herb is often used to create some Chinese medicines.

The following careers are at a higher risk of chemical exposure:

  • Dry Cleaners
  • Painters
  • Autoworkers
  • Truck drivers
  • Paper manufactures
  • Metal workers
  • Plumbers
  • Hairdressers
  • Tire and rubber workers
  • Chemical workers
  • Petroleum workers
Diagnosis

Diagnosis of Upper Tract Urothelial Carcinoma

Often times a CT scan, usually a CT urogram is done. Somtimes depending on the kidney function, a MR urogram, which is MRI test, can be used instead. Somtimes the urologist has to diagnose UTUC by looking into the ureter and kidney.

Retrograde pyelogram is where a urologist takes the patient to the operating roomand uses a tiny camera passed up the urethra into the bladder and up into the ureter. Then some contrast dye is injected into the ureter, which then fills up the collecting system and can demonstrate a tumor.

A simple urine sample called a urine cytology is often helpful. The pathologist looks under the microscope and tells us that these are cancerous cells that are coming from the urinary system.

It’s not a very sensitive test but it is a specific test. So see if a tumor is there then we have to use a camera and a very small scope to go and look at the ureter and the renal pelvis and try to get a biopsy.

Treatment

Treatment for Ureteral Cancer and Upper Tract Urothelial Carcinoma

There are two types of treatment for upper tract urothelial carcinomas:

  • Nephron sparing or conservative management which means we try to save the entire kidney, or part of the kidney, and try to preserve kidney function. We try to ablate and destroy the tumor using a small camera up in to the ureter and kidney. Sometimes we give chemotherapy or immunotherapy in the pelvis or the ureter.
  • Robotic surgical treatment depending on the location of the tumor, we remove all or part of the ureter, kidney and bladder to remove the cancer.

New Conservative Treatment

A drug known as mitomycin-c, a chemotherapy drug, was initially developed as an antibiotic in 1963. It turned out to be fairly toxic as an antibiotic, but effective to treat cancers. We have used this for urothelial cancers in the bladder doing washes or instillations into the bladder.

How the drug is delivered in very important. We converted the liquid form of this drug to a gel form so it can stay in the kidney or ureter. This is a topical therapy, similar to putting cream on your skin, except it will be placed inside for better absorption.

Immunotherapy

These specific drugs are generally called checkpoint blockade. UTUC has a high rate of mutations and unstable genes and makes them more susceptible to immunotherapy. Doctors will not use immunotherapy for treating patients with low grade disease or localized disease at this time, but that may be part of the treatment in the future.
The second category of treatments is for more aggressive disease and for these patients we have to remove the kidney and the ureter, even sometimes the bladder. If patients have more aggressive disease as with stage 2 or 3 UTUC then we use radical surgery with or without chemotherapy. In addition to removing the kidney, ureter and part of the bladder, we also have to remove the lymph nodes around the ureter and the kidney. Typically this is done with minimally invasive surgery, like robotic surgery, where the incisions are small.

If the cancer has spread or appears invasive past the ureter or kidney then we need to add in chemotherapy, sometimes before and after surgery. Chemotherapy has been shown to improve survival. If there is locally advanced disease sometimes giving the chemotherapy before removing the kidney can shrink the tumor and improve the chance of resection, depends on the stage of the disease and if there is metastatic distant spread of the disease. The chemotherapy can go between two to six months. When we remove the kidney and the ureter, the kidney function can decreases because only one kidney.

Staging

Staging

Stage 0, or stage TA or TIS

Stage 0, or stage TA or TIS is a tumor that is just involving the mucosa, the lining on the top. This occurs in 31% of patients with upper tract urothelial carcinoma.

Stage 1

Stage 1 occurs in 25% of patients, and that is when the tumor not only invades the mucosa, but the lamina propria. The lamina propria is a basement membrane, and there are some lymphatics and blood supply there where the tumor, if it sits there long enough, or if it’s aggressive, may actually spread.

Stage 2

Stage 2 muscle-invasive upper tract urothelial carcinoma, tumors not only invade the mucosa, not only invade the lamina propria, but they also invade the muscle lining of the ureter or the renal pelvis. This occurs in 14% of patients.

Stage 3

Stage 3 cancers occur in 24% of patients. It involves the mucosa, the lamina propria, and the muscle. In the kidney, it can actually grow from the renal pelvis into the kidney or the fat around the renal pelvis or ureter.

Stage 4

Stage 4 upper tract urothelial carcinoma can involve surrounding organs or, if it spreads to lymph nodes in the lung or in the retroperitoneum, it would also be considered locally advanced or stage 4 upper tract urothelial carcinoma. This occurs in about 6% of patients.

Grading:

  • 35% are low grade or non-aggressive tumors
  • 65% of the times are high grade or  aggressive

When to See a Provider

Submit an online request for an appointment or call 310-582-7137  if you have any persistent signs and symptoms that worry you. Symptoms can include blood in the urine, painful urination, or side and back pain.