Incidence and Mortality

Transitional cell cancer of the renal pelvis accounts for only 7% of all kidney tumors, and transitional cell cancer of the ureter accounts for only 4% of upper urinary tract tumors. These cancers are 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 urothelial wall or with distant metastases usually cannot be cured with available forms of treatment.

Prognosis

The major prognostic factor at the time of diagnosis of upper tract transitional cell cancer is the depth of infiltration into or through the uroepithelial wall.

Most superficial tumors are likely to be well differentiated, while infiltrative tumors are likely to be poorly differentiated. The incidence of synchronous or metachronous contralateral upper tract cancers ranges from 2% to 4%; the incidence of subsequent bladder cancer after previous upper tract transitional cell cancer ranges from 30% to 50%.[1] When involvement of the upper tract is diffuse (involving both the renal pelvis and ureter), the likelihood of subsequent bladder cancer increases to 75%. DNA ploidy has not added significant prognostic information beyond that provided by stage and grade.[2]

Diagnostics

Even if ureteroscopy and pyeloscopy are successfully implemented, accurate assessment of depth of invasion is difficult.

Treatment Management and Survivorship

Total excision of the ureter with a bladder cuff, renal pelvis, and kidney is recommended to provide the greatest likelihood of cure.

References

1. Krogh J, Kvist E, Rye B: Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences. Br J Urol 67 (1): 32-6, 1991. [PubMed: 1993274]
2. Corrado F, Ferri C, Mannini D, et al.: Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis. J Urol 145 (6): 1159-63, 1991. [PubMed: 2033684]

AJCC Stage Groupings and TNM Definitions

The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define carcinoma of the renal pelvis and ureter.[6]

Patients with localized disease may be classified into three groups:

• Group 1: Low-grade tumor confined to the urothelium without lamina propria invasion (papilloma grade I transitional cell cancer).
• Group 2: Grade I–III carcinomas without demonstrable subepithelial invasion or focal microscopic invasion or papillary carcinomas with carcinoma in situ and/or carcinoma in situ elsewhere in the urothelium.
• Group 3: High-grade tumors that have infiltrated the renal pelvic wall, renal parenchyma, or both but remain confined to the kidney. Infiltration of muscle in the upper tract may not be associated with as much potential for distant dissemination as appears to be the case for bladder cancer.

• Group 4: Extension of tumors beyond the renal pelvis or parenchyma and invasion of peripelvic and perirenal fat, lymph nodes, hilar vessels, and adjacent tissues.

• Spread of the tumor to distant tissues.

Each of these classifications has been subclassified into categories of unicentricity or multicentricity. The latter category indicates a more pervasive tumor diathesis and generally a less favorable prognosis.

Although the classifications listed above have prognostic significance, they can be determined only at the time of nephroureterectomy, which is the treatment of choice for patients with this disease. Because of the high incidence of tumor recurrence within the intramural ureter among patients who have had incomplete excision of this area, nephroureterectomy includes the entire ureter and a margin of periureteral orifice mucosa (i.e., bladder cuff).

A TNM staging system has demonstrated accurate predictions of survival. The TNM staging system may be a better predictor of prognosis than tumor grade, although both are strongly predictive of survival. Median survival for patients with tumors confined to the subepithelial connective tissue was 91.1 months, compared with 12.9 months for patients with tumors invading the muscularis and beyond, in one report. Flow cytometry analysis identifies low-stage, low-grade tumors at high risk of recurrence by virtue of their aneuploid histograms.

References

1. Grossman HB, Schwartz SL, Konnak JW: Ureteroscopic treatment of urothelial carcinoma of the ureter and renal pelvis. J Urol 148 (2 Pt 1): 275-7, 1992. [PubMed: 1635116]
2. Batata M, Grabstald H: Upper urinary tract urothelial tumors. Urol Clin North Am 3 (1): 79-86, 1976. [PubMed: 936370]
3. Cummings KB, Correa RJ, Gibbons RP, et al.: Renal pelvic tumors. J Urol 113 (2): 158-62, 1975. [PubMed: 1113408]
4. Nocks BN, Heney NM, Daly JJ, et al.: Transitional cell carcinoma of renal pelvis. Urology 19 (5): 472-7, 1982. [PubMed: 7080318]
5. Heney NM, Nocks BN, Daly JJ, et al.: Prognostic factors in carcinoma of the ureter. J Urol 125 (5): 632-6, 1981. [PubMed: 7230332]
6. Renal Pelvis and Ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, 749–55.
7. Huben RP, Mounzer AM, Murphy GP: Tumor grade and stage as prognostic variables in upper tract urothelial tumors. Cancer 62 (9): 2016-20, 1988. [PubMed: 3167813]
8. Blute ML, Tsushima K, Farrow GM, et al.: Transitional cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry. J Urol 140 (5): 944-9, 1988. [PubMed: 3172363]

Treatment Options for Localized Transitional Cell Cancer of the Renal Pelvis and Ureter

Treatment options for localized transitional cell cancer of the renal pelvis and ureter include the following:

1. Nephroureterectomy with bladder cuff excision.
2. Segmental resection of ureter, only if the tumor is superficial and located in the distal third of the ureter.
3. Electroresection and fulguration or laser fulguration, if the tumor is superficial (under clinical evaluation).
4. Any parenchymal sparing procedure (segmental resection; ureteroscopic or percutaneous resection/fulguration/laser destruction), if the renal unit is solitary or renal function is depressed (under clinical evaluation).
5. Intrapelvic or intraureteral cytotoxic/immunotherapy (under clinical evaluation). The dramatic success reported with intravesical cytotoxic (thiotepa, mitomycin, doxorubicin) or immunologic/inflammatory (Bacillus Calmette Guerin [BCG], interferon) therapy for superficial transitional cell cancers in the bladder has led to the occasional use of these agents in the treatment of upper tract cancers. Long-term follow-up of the results of such treatments has generally not been reported. The efficacy of this approach cannot be assessed, largely because experience has been limited to patients whose compromised clinical status (solitary kidney, renal failure, medical risks for surgery) may have influenced clinical outcome. The use of this approach is limited by the following:

   • The extent of disease in the renal pelvis.
   • The access that these agents may have to the area of disease.
   • The sensitivity of the cancer being treated.
   • The adequacy and accuracy of initial tumor staging and continued monitoring.
6. Laser vaporization/coagulation (under clinical evaluation). Transurethral and percutaneous access to the upper tract have permitted the use of laser therapy in the control of superficial upper tract transitional cell cancers. This approach is dependent on accurate staging and adequate visualization of the lesions that need to be coagulated. Results of this approach are too preliminary to assess. Therapeutic efficacy, however, will depend on staging accuracy at initial treatment and the ease of monitoring such patients for disease recurrence and possible progression.

The development of new instrumentation for endourological treatment of upper tract transitional cell cancer has provided new options for regional management of these cancers. Introduction of electrofulguration and resection instruments or laser probes either transureterally or percutaneously, may permit destruction of a primary cancer. Introduction of cytotoxic agents has also been used. Although a biopsy can be taken for staging purposes, its accuracy remains to be determined. The efficacy of treatment by these maneuvers has not been established.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Sternberg CN, Yagoda A, Scher HI, et al.: Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer 64 (12): 2448-58, 1989. [PubMed: 2819654]
2. Harker WG, Meyers FJ, Freiha FS, et al.: Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. J Clin Oncol 3 (11): 1463-70, 1985. [PubMed: 4056840]
3. Loehrer PJ, Einhorn LH, Elson PJ, et al.: A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 10 (7): 1066-73, 1992. [PubMed: 1607913]
4. Roth BJ: Preliminary experience with paclitaxel in advanced bladder cancer. Semin Oncol 22 (3 Suppl 6): 1-5, 1995. [PubMed: 7541150]
5. Witte RS, Elson P, Bono B, et al.: Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol 15 (2): 589-93, 1997. [PubMed: 9053481]
6. Einhorn LH, Roth BJ, Ansari R, et al.: Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma. J Clin Oncol 12 (11): 2271-6, 1994. [PubMed: 7525884]
7. Pollera CF, Ceribelli A, Crecco M, et al.: Weekly gemcitabine in advanced bladder cancer: a preliminary report from a phase I study. Ann Oncol 5 (2): 182-4, 1994. [PubMed: 8186164]
8. Sweeney CJ, Roth BJ, Kabbinavar FF, et al.: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol 24 (21): 3451-7, 2006. [PubMed: 16849761]

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of transitional cell cancer of the renal pelvis and ureter. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

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The lead reviewer for Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment is:

• Timothy Gilligan, MD (Cleveland Clinic Taussig Cancer Institute)

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PDQ® Adult Treatment Editorial Board. PDQ Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/kidney/hp/transitional-cell-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389446]

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