by Dr. C.H. Weaver M.D. updated 4/2023
Overall, 92% of all urothelial cancers occur in the bladder but about 7-8% of urothelial occur in the upper lining of the kidney called the calyx and renal pelvis or in the ureter. Cancers that occur in the upper portion of the urothelial system can occur anywhere from the inner linings of the kidney, down the ureter and are collectively referred to as Upper Tract Urothelial Cancers (UTUC).1
Individuals with the inherited cancer syndrome known as Lynch Syndrome are at increased risk of developing UTUC. In fact, UTUC is the third most common type of cancer that occurs in patients with Lynch, the most common being colon cancer. One in five patients with UTUC have a variant of Lynch Syndrome and all patients with these cancers should undergo genetic testing.
UTUC are typically treated with surgical removal of the cancer.
- Fulguration and laser surgery are also used to treat the primary cancer. Fulguration is a surgical procedure that destroys tissue using an electric current. A tool with a small wire loop on the end is used to remove the cancer or to burn away the cancer with electricity.
- Laser surgery uses a laser beam (narrow beam of intense light) as a knife to remove the cancer. A laser beam can also be used to kill the cancer cells and this procedure may also be called or laser fulguration.
The more advanced the stage of the UTUC the more likely the cancer is to recur following treatment with surgery alone. In order to reduce the risk of recurrence doctors administer adjuvant therapy after surgery. Adjuvant therapy may consist of chemotherapy, immunotherapy, or precision cancer medicines.
Research published in 2020 has demonstrated that chemotherapy after surgery halves risk of UTUC coming back. Patients given chemotherapy within three months of surgery saw the risk of their cancer coming back or spreading reduced and were much more likely to live cancer free for three years or more.
The POUT clinical trial led by researchers at The Institute of Cancer Research, London enrolled 261 people with cancer of the ureter and renal pelvis who were treated with either active surveillance to spot signs of their cancer coming back after surgery or a simple combination of Gemzar (gemcitabine) and platinum chemotherapy. The researchers found that treating patients with platinum-based chemotherapy after surgery reduced the risk of dying from the cancer; 71% of patients treated with the chemotherapy regimen survived for three years or more after without cancer recurrence compared with 46% of patients who were on surveillance.2
A Non-Surgical Option for Low Grade UTUC
Jelmyto (mitomycin gel) is the first “approved” therapy to treat low-grade UTUC. In general, low-grade tumors are not invasive and very rarely spread from the kidney or ureter. However, they often recur, and management involves treating visible tumors and trying to preserve the urinary tract, as these tumors are more likely to recur in the urinary system than they are to spread.
The FDA approved Jelmyto based on the results of a clinical trial involving 71 patients with low-grade UTUC. These patients had never undergone treatment or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor (a tumor shaped like a small mushroom with its stem attached to the inner lining of an organ). Patients received Jelmyto once a week for six weeks. A complete response was found in 41 of the 71 patients (58%) following six treatments of Jelmyto administered weekly. Nineteen patients (46%) who achieved a complete response continued to have a complete response greater than 12 months from treatment. Common side effects include ureteric obstruction, flank, urinary tract infections, hematuria, fatigue, nausea, abdominal pain, and painful or difficult urination.
“This is the first FDA approval specifically for patients with low-grade UTUC and provides an option for some patients who may otherwise require a nephroureterectomy,” said FDA Chief Richard Pazdur.
In addition to testing for Lynch Syndrome all patients with UTUC should discuss the role of genomic biomarker testing of their cancer with their treating physician in order to determine if newer precision cancer medicines and immunotherapy might be an additional treatment option.
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