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HomeHealth articlesupper tract urothelial carcinomaHow to Manage Upper Tract Urothelial Carcinoma?

Management Of Upper Tract Urothelial Carcinoma

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4 min read


Upper tract urothelial carcinoma is a rare urologic cancer with no major increase in survival rates. This article stresses the importance of multimodality care.

Written by

Dr. Chandana. P

Medically reviewed by

Dr. Madhav Tiwari

Published At March 30, 2023
Reviewed AtDecember 1, 2023


Urothelial carcinoma is the fourth most prevalent kind of solid cancer. The majority of situations (90 to 95 percent) occur in the lower urinary tracts (urinary bladder and urethra), with the remaining occurring in the upper urinary tract (renal calyces, renal pelvis, and ureter). Upper tract urothelial carcinomas (UTUC) share a similar histological pattern as lower tract urothelial carcinomas. Still, they have been discovered to exhibit different phenotypic and genotypic (genetic and epigenetic) variances, prompting physicians to refer to them as dissimilar twins. UTUCs are rare, accounting for five to ten percent of urothelial carcinomas (UCs). UTUC has a distinct natural history from UCB (urinary carcinoma of the bladder), and at diagnosis, UTUC has a greater incidence of local invasion. Hereditary nonpolyposis colorectal cancer has been associated with familial or hereditary UTUCs, and these individuals can be tested during screening.

What Are the Risk Factors of Upper Tract Urothelial Carcinoma?

  • Several environmental variables influence the development of UTUC. Exposure to tobacco enhances the likelihood from 2.5 to 7. UTUC "amino tumors" were previously linked to occupational exposure to carcinogenic aromatic amines such as benzidine and b-naphthalene.

  • The average exposure period required to develop UTUC is seven years, with a delay of up to 20 years following exposure termination.

  • Numerous investigations have shown that aristolochic acid, present in Aristolochia fangchi and clematis plants, has carcinogenic potential.

  • The aristolochic acid-derivative d-aristolactam is linked to a particular mutation in the p53 gene at codon 139, which is seen in individuals with UTUC who have nephropathy caused by Chinese herbs or Balkan endemic nephropathy.

  • Even though the frequency of Balkan endemic nephropathy is decreasing, aristolochic acid serves an important role in the pathogenesis of this nephropathy.

What Are the Underlying Molecular Pathways for UTUC?

  • The molecular architecture of UTUC is poorly understood and frequently hypothesized from bladder urothelial carcinoma. Yet, the two have considerable epidemiological and clinicopathological disparities, indicating that distinct genetic traits cause them.

  • Understanding these molecular pathways is crucial because it offers the possibility of possible therapeutic targets.

  • Sfakianos et al. and colleagues recently developed a unique next-generation sequencing technique to discover somatic mutations and copy number variations in 300 cancer-associated genes in tumor and germline DNA from UTUC (n=83) and bladder urothelial carcinoma (n=102) patients.

  • Although the spectrum of mutant genes was comparable, the frequency of variations in certain repeatedly mutated genes, such as FGFR3, HRAS, TP53, and RB1, differed. Compared to high-grade bladder urothelial carcinoma, high-grade UTUC had more FGFR3 and HRAS mutations and less TP53 and RB1.

How Is Upper Tract Urothelial Carcinoma Managed?

  • Kidney-Sparing Surgery:

    • Kidney-sparing surgery (KSS) for low-risk UTUC minimizes the morbidity of radical surgery while maintaining oncological results and kidney function.

    • It is the recommended strategy in low-risk tumors, with survival being comparable following kidney-sparing surgery (KSS) versus radical nephroureterectomy (RNU).

    • This approach should thus be considered in all low-risk patients, regardless of the condition of the contralateral kidney. Moreover, it might be explored in individuals with severe renal insufficiency or a single kidney.

  • Ureteroscopy:

    • Endoscopic ablation can be explored in individuals with clinically low-risk malignancy in the following cases:

      • For biopsies, laser generators and pliers are provided.

      • If a flexible instead of a rigid ureteroscope is accessible, use it.

      • The patient is warned of needing an early, closer, and strict observation.

      • Complete resection of the tumor or elimination is possible.

      • Yet, there is a danger of understating and under-grading with endoscopic treatment.

  • Percutaneous Access:

    • Percutaneous intervention should be performed for low-risk UTUC in the renal pelvis. This procedure may treat low-risk tumors in the lower calyceal system that are not accessible or hard to manage using flexible ureteroscopy.

    • Nevertheless, this procedure is being utilized less frequently due to the advent of better endoscopic equipment, like the distal-tip deflection of modern ureteroscopes. With a percutaneous approach, the possibility of tumor seeding exists.

  • Segmental Ureteral Resection:

    • By sparing the ipsilateral (same side) kidney, segmental ureteral resection with broad margins gives appropriate histopathological samples for staging and grading of cancer. Lymphadenectomy (excision of the regional lymph nodes) can also be done during segmental ureteral resection.

    • Total distal ureterectomy with neo-cystostomy (surgical bladder implantation) is appropriate for low-risk distal ureter tumors, which cannot be excised fully endoscopically, and high-risk tumors when KSS for preserving renal function. The iliac and lumbar ureters fail faster than the distal pelvic ureter.

    • Partial pyelotomy or partial nephrectomy is exceedingly unusual. Open excision of tumors of the renal pelvis or calyces has been practically stopped.

  • Adjuvant Topical Agents:

    • During kidney-sparing therapy or for the treatment of CIS (carcinoma in situ), antegrade (upwards) administration of bacillus Calmette-Guérin (BCG) vaccine or Mitomycin C in the upper urinary tract by percutaneous nephrostomy using a three-valve system open at 20 cm (after total tumor removal) is possible.

    • Retrograde (downwards) instillation through a ureteric stent is also employed. However, it is risky because of the possibility of a ureteral blockage and subsequent pyelovenous inflow following instillation or perfusion.

    • Reflux from a double-J stent has been employed. However, it is not recommended because it frequently does not reach the renal pelvis.

  • Radical Nephroureterectomy (RNU):

    • Irrespective of the tumor site, open radical nephroureterectomy (RNU) with bladder cuff resection is the gold standard for high-risk UTUC. RNU must adhere to oncological principles, such as avoiding tumor seeding by limiting entrance into the urinary system while removing.

    • The distal ureter and its opening are excised since there is a high probability of tumor recurrence in this location. It is difficult to visualize or access the proximal ureter once removed.

    • After RNU, the distal ureter and bladder cuff should be removed. Various procedures, such as plucking, stripping, transurethral resection of the intramural ureter, and intussusception, have been suggested to aid distal ureter excision. Except for ureteral stripping, all of these procedures are equal to bladder cuff excision.

  • Laparoscopic RNU:

    • Several examples of retroperitoneal metastatic spread and metastases through the trocar system following the management of massive tumors in a pneumoperitoneum environment have been described.

    • Various measures can be taken to reduce the risk of tumor spillage:

      • Do not penetrate the urinary tract.

      • Avoid putting equipment in direct contact with the tumor.

      • Laparoscopic RNU must be performed within a closed system. To avoid tumor morcellation, utilize an endo bag for tumor resection.

      • The kidney and ureter must be extracted together with the bladder cuff.

      • Until proven otherwise, invasive or huge tumors are contraindicated for laparoscopic RNU.


A complete understanding of the epidemiological variables and molecular mechanisms is necessary for successful UTUC management. For low-risk conditions, kidney-sparing surgery is used, and for high-risk diseases, a radical nephroureterectomy is performed. With increased scientific evidence and research in urothelial carcinoma, perioperative immunotherapy and chemotherapy may be explored.

Frequently Asked Questions


What Are the Chances of Survival for Individuals Diagnosed With Upper Tract Urothelial Carcinoma?

Generally speaking, the 5-year survival rates for UTUC are as follows:
- Localized Stage: 80 percent or more survival rate, indicating a relatively good prognosis for those with early-stage UTUC.
- Locally Advanced Stage: Survival rates range from 40 percent to 70 percent, reflecting the challenges posed by more advanced diseases.
- Metastatic Stage: Survival rates range from 10 percent to 30 percent or less, highlighting the challenges in treating cancer that has spread to distant areas.


Where Does Urinary Tract Urothelial Carcinoma Most Frequently Occur in the Body?

The most common site for upper urinary tract urothelial carcinoma (UTUC) is the renal pelvis. Urothelial carcinoma that originates in the renal pelvis is often referred to as renal pelvis carcinoma. While UTUC can also occur in the ureters, which are the tubes that connect the kidneys to the bladder, tumors originating in the renal pelvis are more prevalent. 


How Do Upper Tract Urothelial Carcinoma and Bladder Cancer Differ From Each Other?

Upper tract urothelial carcinoma (UTUC) and bladder cancer are both forms of urothelial carcinoma, a type of cancer that originates in the urothelial cells lining the urinary tract. However, they differ in terms of their location within the urinary tract and their characteristics. 


Is There a Cure for Urothelial Carcinoma?

The potential for curing urothelial carcinoma (UC) depends on several factors, including the stage of cancer at the time of diagnosis, the specific location within the urinary tract, the grade of the tumor, the patient's overall health, and the effectiveness of the treatments employed. 


What Treatment Is Typically Considered the Primary Option for Urothelial Carcinoma?

The best course of action for treating urothelial carcinoma (UC) relies on a number of variables, including the cancer's stage and grade, where it is located in the urinary tract, the patient's general health, and personal preferences. Some of them are transurethral resection of bladder tumors (TURBT), surgery, chemotherapy, radiation therapy, and immunotherapy.


At What Age Is Upper Tract Urothelial Carcinoma Commonly Diagnosed?

Upper tract urothelial carcinoma (UTUC) can occur at any age, but it is more commonly diagnosed in older individuals. The risk of developing UTUC tends to increase with age, particularly after the age of 60. 


Does Urothelial Carcinoma Typically Cause Pain?

Urothelial carcinoma itself might not always cause pain, especially in its early stages. However, as the cancer progresses or if it affects certain parts of the urinary tract, it can lead to various symptoms, including pain. Based on variables like the location of the tumor, the stage of the malignancy, and personal sensitivity, the presence and intensity of pain can differ.


What Category of Cancer Does Urothelial Carcinoma Fall Under?

Urothelial carcinoma (UC) is a type of cancer that originates in the urothelial cells, which are the cells that line the inside of the urinary tract. The urinary tract includes various parts of the body involved in urine production and elimination, such as the bladder, ureters (tubes that connect the kidneys to the bladder), and renal pelvis (the funnel-like structure in the kidney where urine collects).


Is It Common for Urothelial Carcinoma to Metastasize to Other Organs in the Body?

Yes, urothelial carcinoma (UC) can spread to other organs, a process known as metastasis. If the cancer cells invade nearby tissues or travel through the bloodstream or lymphatic system to other parts of the body, it can become metastatic. Common sites of metastasis for urothelial carcinoma include regional lymph nodes, bones, lungs, and liver.


Is Urothelial Carcinoma Known for Its Slow Growth Rate as a Cancer?

Urothelial carcinoma (UC) can vary in its growth rate, and whether it is considered slow-growing or fast-growing depends on factors such as the stage and grade of the cancer, as well as the individual characteristics of the tumor. Urothelial carcinoma encompasses a range of behaviors, from indolent (slow-growing) to aggressive.


Is Urothelial Carcinoma Typically Considered an Aggressive Form of Cancer?

High-grade urothelial carcinomas are characterized by more abnormal-looking cancer cells that tend to grow and divide rapidly. These tumors are more aggressive and can invade deeper into the bladder wall or spread to other parts of the urinary tract. Urothelial carcinomas that have invaded the muscle layer of the bladder wall or extended to other parts of the urinary tract are considered invasive. Invasive UCs are generally more aggressive due to their potential to spread to nearby lymph nodes or distant organs.


Is urothelial carcinoma a commonly encountered type of cancer?

Urothelial carcinoma (UC) is not considered rare, but its frequency can vary based on the specific location within the urinary tract and other factors. Urothelial carcinoma can occur in different parts of the urinary system, including the bladder, upper urinary tract (renal pelvis and ureters), urethra, and urethral diverticulum. The frequency of UC varies depending on where it originates.


What Measures Can Be Taken to Reduce the Risk of Developing Urothelial Carcinoma?

While there is no guaranteed way to completely prevent urothelial carcinoma, there are several steps to reduce the risk of developing this type of cancer:
- Quit Smoking: Tobacco smoke is a significant risk factor for urothelial carcinoma, particularly bladder cancer. The chance of getting this cancer can be considerably decreased by quitting smoking.
- Avoid Exposure to Harmful Chemicals: Minimize exposure to chemicals and substances that are known or suspected carcinogens. 
- Stay Hydrated: Drinking a lot of water can help possible carcinogens in urine become less concentrated and have less contact with urothelial cells.
- Maintain a Healthy Diet: A diet rich in fruits, vegetables, whole grains, and lean proteins can support overall health and potentially reduce the risk of cancer.


What Are the Potential Health Issues or Complexities Associated With Urothelial Carcinoma?

- Invasion and Metastasis: Left untreated or in advanced stages, UC can invade nearby tissues and organs or spread (metastasize) to distant sites, leading to more serious complications and a worse prognosis.
- Obstruction: Tumors in the urinary tract, especially in the ureters or urethra, can obstruct the flow of urine. This obstruction can lead to kidney problems, urinary tract infections, and pain.
- Kidney Dysfunction: UC in the upper urinary tract (renal pelvis or ureters) can affect kidney function and potentially lead to kidney damage or failure.
- Hematuria and Urinary Symptoms: Blood in the urine (hematuria) is a common symptom of UC, which can lead to pain or discomfort during urination. Frequent or urgent urination can also affect the quality of life.
- Urinary Tract Infections (UTIs): UC can increase the risk of urinary tract infections, which can cause pain, fever, and discomfort.
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Dr. Madhav Tiwari
Dr. Madhav Tiwari

General Surgery


upper tract urothelial carcinoma
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