General Information About Transitional Cell Cancer of the Renal Pelvis and Ureter
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Incidence and Mortality
Transitional cell cancer of the renal pelvis accounts for only 7% of allkidney tumors, and transitional cell cancer of the ureter accounts for only4% of upper urinary tract tumors. These cancers are curable in more than 90% of patients ifthey are superficial and confined to the renal pelvis or ureter. Patients withdeeply invasive tumors that are confined to the renal pelvis or ureterhave a 10% to 15% likelihood of cure. Patients with tumors with penetrationthrough the urothelial wall or with distant metastases usually cannot be curedwith available forms of treatment.
Prognosis
The major prognostic factor atthe time of diagnosis of upper tract transitional cell cancer is the depth ofinfiltration into or through the uroepithelial wall.
Most superficial tumors are likely to be well differentiated, while infiltrative tumorsare likely to be poorly differentiated. The incidence ofsynchronous or metachronous contralateral upper tract cancers ranges from 2% to4%; the incidence of subsequent bladder cancer after previous upper tracttransitional cell cancer ranges from 30% to 50%.[1] When involvement of theupper tract is diffuse (involving both the renal pelvis and ureter), thelikelihood of subsequent bladder cancer increases to 75%. DNAploidy has not added significant prognostic information beyond that provided bystage and grade.[2]
Diagnostics
Even ifureteroscopy and pyeloscopy are successfully implemented, accurate assessmentof depth of invasion is difficult.
Treatment Management and Survivorship
Total excision of the ureterwith a bladder cuff, renal pelvis, and kidney is recommended toprovide the greatest likelihood of cure.
References
- 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 Abstract]
- 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 Abstract]
Cellular Classification of Transitional Cell Cancer of the Renal Pelvis and Ureter
Most upper tract uroepithelial tumors are of transitional cellhistology. Squamous cell cancer (SCC) of the urinary tract makes up less than 15%of the tumors of the renal pelvis and a smaller percentage of ureteral tumors. SCC is often associated with chronic calculus disease and infection.
Grade of transitional cell cancer of the upper tract has generally been foundto correlate with stage. Superficial tumors are generally grade I or II,whereas most infiltrative tumors are grades III and IV. Prognosisis worse for patients with high-grade (grades III and IV) tumors than for thosewith low-grade (grades I and II) tumors.
Stage Information for Transitional Cell Cancer of the Renal Pelvis and Ureter
Though comparable in many respects to staging systems described for bladdercancer, unique structural aspects of the renal pelvis and ureter have led toseveral differences in the classification schema of tumors that involve theupper tracts. Clinical staging is based on a combination of radiographicprocedures (e.g., intravenous pyelogram and computed tomographic scans) and,more recently, ureteroscopy and biopsy.
The advent of rigid and flexible ureteroscopic techniques has permittedendoscopic access to the ureter and renal pelvis. This may permit greateraccuracy in preoperative definition of the stage and grade of an upper tractneoplasm. In addition, fulguration and endourological access permit resectionor laser coagulation of highly selected low-stage, low-grade lesions of theureters.[1] However, this approach is still under clinical evaluation becausethere is the possibility of inaccurate assessment of the stage and extent ofdisease, and the adequacy and risks of such treatment have not yet beendefined.[2-5]
Because of the inaccessibility of ureteral and pelvic anatomy, accurate stagingrequires pathological analysis of the surgically excised specimen.
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]
| Stage | TNM | Definition |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Renal pelvis and ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 749–55. | ||
| 0a | Ta, N0, M0 | Ta = Papillary noninvasive carcinoma. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| 0is | Tis, N0, M0 | Tis = Carcinoma in situ. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Definition |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Renal pelvis and ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 749–55. | ||
| I | T1, N0, M0 | T1 = Tumor invades subepithelial connective tissue. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Definition |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Renal pelvis and ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 749–55. | ||
| II | T2, N0, M0 | T2 = Tumor invades the muscularis. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Definition |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Renal pelvis and ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 749–55. | ||
| III | T3, N0, M0 | T3 = For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or into the renal parenchyma. For ureter only: Tumor invades beyond muscularis into periureteric fat. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Definition |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Renal pelvis and ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 749–55. | ||
| IV | T4, N0, M0 | T4 = Tumor invades adjacent organs, or through the kidney into the perinephric fat. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Any T, N1, M0 | TX = Primary tumor cannot be assessed. | |
| T0 = No evidence of primary tumor. | ||
| Ta = Papillary noninvasive carcinoma. | ||
| Tis = Carcinoma in situ. | ||
| T1 = Tumor invades subepithelial connective tissue. | ||
| T2 = Tumor invades the muscularis. | ||
| T3 = For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or into the renal parenchyma. For ureter only: Tumor invades beyond muscularis into periureteric fat. | ||
| T4 = Tumor invades adjacent organs, or through the kidney into the perinephric fat. | ||
| N1 = Metastasis in a single lymph node, ≤2 cm in greatest dimension. | ||
| M0 = No distant metastasis. | ||
| Any T, N2, M0 | Any T = See descriptions above in this table, stage IV, Any T, N1, M0. | |
| N2 = Metastasis in a single lymph node, >2 cm; or multiple lymph nodes. | ||
| M0 = No distant metastasis. | ||
| Any T, Any N, M1 | Any T = See descriptions above in this table, stage IV, Any T, N1, M0. | |
| NX = Regional lymph nodes cannot be assessed. | ||
| N0 = No regional lymph node metastasis. | ||
| N1 = Metastasis in a single lymph node, ≤2 cm in greatest dimension. | ||
| N2 = Metastasis in a single lymph node, >2 cm; or multiple lymph nodes. | ||
| M1 = Distant metastasis. | ||
Patients may also be designated as having localized, regional, or metastaticdisease, as follows:
Localized
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 orfocal 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, renalparenchyma, or both but remain confined to the kidney. Infiltration ofmuscle in the upper tract may not be associated with as much potential fordistant dissemination as appears to be the case for bladder cancer.
Regional
- Group 4: Extension of tumors beyond the renal pelvis or parenchyma and invasionof peripelvic and perirenal fat, lymph nodes, hilar vessels, and adjacenttissues.
Metastatic
- Spread of the tumor to distant tissues.
Each of these classifications has been subclassified into categories ofunicentricity or multicentricity. The latter category indicates a more pervasive tumordiathesis and generally a less favorable prognosis.
Although the classifications listed above have prognostic significance, theycan be determined only at the time of nephroureterectomy, which is thetreatment of choice for patients with this disease. Because of the highincidence of tumor recurrence within the intramural ureter among patients whohave had incomplete excision of this area, nephroureterectomy includesthe entire ureter and a margin of periureteral orifice mucosa (i.e., bladder cuff).
A TNM staging system has demonstrated accuratepredictions of survival. The TNM staging system may be a better predictor ofprognosis than tumor grade, although both are strongly predictive of survival. Median survival for patients with tumors confined to the subepithelialconnective tissue was 91.1 months, compared with 12.9 months for patients withtumors invading the muscularis and beyond, in one report. Flow cytometry analysisidentifies low-stage, low-grade tumors at high risk of recurrence by virtue oftheir aneuploid histograms.[7,8]
References
- 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 Abstract]
- Batata M, Grabstald H: Upper urinary tract urothelial tumors. Urol Clin North Am 3 (1): 79-86, 1976.[PUBMED Abstract]
- Cummings KB, Correa RJ, Gibbons RP, et al.: Renal pelvic tumors. J Urol 113 (2): 158-62, 1975.[PUBMED Abstract]
- Nocks BN, Heney NM, Daly JJ, et al.: Transitional cell carcinoma of renal pelvis. Urology 19 (5): 472-7, 1982.[PUBMED Abstract]
- Heney NM, Nocks BN, Daly JJ, et al.: Prognostic factors in carcinoma of the ureter. J Urol 125 (5): 632-6, 1981.[PUBMED Abstract]
- Renal Pelvis and Ureter. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, 749–55.
- 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 Abstract]
- 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 Abstract]
Treatment Option Overview for Transitional Cell Cancer of the Renal Pelvis and Ureter
Most patients with renal pelvic transitional cell cancers andureteral cancers undergo total nephroureterectomy withbladder cuff excision. This treatment is because of the rarity of synchronous bilateral renal pelvic neoplasia, the low incidenceof asynchronous development of contralateral upper tract tumors, and theincreased risk of tumor recurrence in the ipsilateral ureter distal to theoriginal pelvic tumor.
Contemplation of anything less than total excision must take into account thepotential risk for tumor recurrence anywhere in the upper tract unit. In otherthan unifocal, low-grade, low-stage renal pelvic tumors, the probable extensiveinvolvement of both contiguous and noncontiguous sites would appear to makesegmental excision an unnecessary option with a potentially serious risk. However, an operative possibility includes segmental excision of a particularlesion. If the extent of a tumor can be determined by intraoperativeassessment and frozen section histological diagnosis confirms a low-grade,unifocal tumor of limited size, then segmental excision is possible. However,this approach should be reserved for highly selected patients such as patients with one kidney or those with decreased renalfunction who require maximal preservation of renal tissue. The likelihoodof tumor recurrence in this setting, and of extension of disease outside therenal pelvis once the pelvis has been violated, is a serious risk that must beheavily weighed in offering a patient this therapeutic option.
Ureteral transitional cell cancer may more readily offer the possibility ofsegmental excision if the absence of proximal disease can be documented. Inthis setting, attention is focused on the ease of reconstruction of the ureterand restoration of ureterovesical continuity. This treatment is most feasible if thecancer is in the distal ureter. If partial ureterectomy is possible andproximal disease has been excluded, then segmental excision and ureteralreimplantation can be performed.
Systematic regional lymph node dissection in conjunction withnephroureterectomy or segmental excision has not been found to enhance theeffectiveness of surgery if tumors are of high grade or high stage because, inthese instances, the overall results are so poor. Correspondingly, lymph nodeinvolvement is uncommon in low-stage disease, and lymphadenectomy is unlikely to remove additional tumor. Lymph node dissection at the timeof nephrectomy may offer prognostic information, but little, if any,therapeutic benefit.
Treatment of Localized Transitional Cell Cancer of the Renal Pelvis and Ureter
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:
- Nephroureterectomy with bladder cuff excision.
- Segmental resection of ureter, only if the tumor is superficial and locatedin the distal third of the ureter.
- Electroresection and fulguration or laser fulguration, if the tumor issuperficial (under clinical evaluation).
- Any parenchymal sparing procedure (segmental resection; ureteroscopic orpercutaneous resection/fulguration/laser destruction), if the renal unit issolitary or renal function is depressed (under clinical evaluation).
- Intrapelvic or intraureteral cytotoxic/immunotherapy (under clinical evaluation). The dramaticsuccess reported with intravesical cytotoxic (thiotepa,mitomycin, doxorubicin) or immunologic/inflammatory (Bacillus Calmette Guerin [BCG], interferon) therapyfor superficial transitional cell cancers in the bladder has led to theoccasional use of these agents in the treatment of upper tract cancers. Long-term follow-up of the results of such treatments has generally not beenreported. The efficacy of this approach cannot be assessed, largely becauseexperience has been limited to patients whose compromised clinical status(solitary kidney, renal failure, medical risks for surgery) may have influencedclinical outcome. The use of this approach is limited by the following:
- The extent ofdisease in the renal pelvis.
- The access that these agents may have to the areaof disease.
- The sensitivity of the cancer being treated.
- The adequacy andaccuracy of initial tumor staging and continued monitoring.
- Laser vaporization/coagulation (under clinical evaluation). Transurethral and percutaneous access tothe upper tract have permitted the use of laser therapy in the control ofsuperficial upper tract transitional cell cancers. This approach is dependenton accurate staging and adequate visualization of the lesions that need to becoagulated. Results of this approach are too preliminary to assess. Therapeutic efficacy, however, will depend on staging accuracy at initialtreatment and the ease of monitoring such patients for disease recurrence andpossible progression.
The development of new instrumentation for endourological treatment of uppertract transitional cell cancer has provided new options for regional managementof these cancers. Introduction of electrofulguration and resection instrumentsor laser probes either transureterally or percutaneously, may permit destructionof 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 notbeen 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.
Treatment of Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
There is no well-documentedsuccess for treatment of extensive regional disease with either radiation therapy or systemic chemotherapy. Patients with extensiveregional disease should consider clinical trials.
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.
Treatment of Metastatic or Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
The prognosis for any patient with metastatic or recurrent transitional cellcancer is poor. The proper management of recurrence depends on the sites ofrecurrence, extent of prior therapy, and individual patient considerations. Chemotherapy regimens that have been effective for metastatic bladdercancer have generally been applied to transitional cell cancers arising fromother sites. Patients with distant metastases have a poor prognosis and canbe offered treatment in a clinical trial.
In patients with metastatic or recurrent transitional cell carcinoma of thebladder, combination chemotherapy has produced high response rates andoccasional complete responses.[1,2] Results from a randomized trial thatcompared methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) withsingle-agent cisplatin in advanced bladder cancer showed a significant advantagewith M-VAC in both response rate and median survival. The overall responserate with M-VAC in this cooperative group trial was 39%.[3]
Other chemotherapy agents that have shown activity in metastatic transitionalcell cancer include the following:[4-8][Level of evidence C3]
- Pacl*taxel.
- Ifosfamide.
- Gallium nitrate.
- Gemcitabine.
- Pemetrexed.
Ifosfamide, gallium nitrate, and pemetrexed have shown limited activity inpatients previously treated with cisplatin.
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
- 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 Abstract]
- 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 Abstract]
- 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 Abstract]
- Roth BJ: Preliminary experience with pacl*taxel in advanced bladder cancer. Semin Oncol 22 (3 Suppl 6): 1-5, 1995.[PUBMED Abstract]
- 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 Abstract]
- 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 Abstract]
- 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 Abstract]
- 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 Abstract]
Latest Updates to This Summary (01/05/2024)
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About This PDQ Summary
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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