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Table of Contents Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Treatment Option Overview
Localized Transitional Cell Cancer of the Renal Pelvis and Ureter
Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
Get More Information From NCI
Changes to This Summary (05/22/2008)
More Information
Purpose of This PDQ 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. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognosis.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information
Transitional cell carcinoma of the renal pelvis, accounting for only 7% of all
kidney tumors, and transitional cell cancer of the ureter, accounting for only
1 of every 25 upper tract tumors, 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 still 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 currently available forms of treatment. 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. However, even if
ureteroscopy and pyeloscopy are successfully implemented, accurate assessment
of depth of invasion is difficult. Therefore, total excision of the ureter
with a bladder cuff, renal pelvis, and kidney is recommended in an attempt to
provide the greatest likelihood of cure.
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 prior 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 development of bladder cancer increases to 75%. DNA
ploidy has not added significant prognostic information beyond that provided by
stage and grade.[2]
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]
Back to Top Cellular Classification
The majority of upper tract uroepithelial tumors are of transitional cell
histology. Squamous cell cancer of the urinary tract constitutes less than 15%
of the tumors of the renal pelvis and a smaller percentage of ureteral tumors
and is often associated with chronic calculus disease and infection.
Grade of transitional cell cancer of the upper tract has generally been found
to correlate with stage. Superficial tumors are generally grade I or II,
whereas the majority of infiltrative tumors are grades III and IV. Prognosis
is worse for patients with high-grade (grades III and IV) tumors than for those
with low-grade (grades I and II) tumors.
Back to Top Stage Information
Though comparable in many respects to staging systems described for bladder
cancer, unique structural aspects of the renal pelvis and ureter have led to
several differences in the classification schema of tumors that involve the
upper tracts. Clinical staging is based on a combination of radiographic
procedures (e.g., intravenous pyelogram and computed tomographic scans) and,
more recently, ureteroscopy and biopsy.
The advent of rigid and flexible ureteroscopic techniques has permitted
endoscopic access to the ureter and renal pelvis. This may permit greater
accuracy in preoperative definition of the stage and grade of an upper tract
neoplasm. In addition, fulguration and endourological access permit resection
or laser coagulation of highly selected low-stage, low-grade lesions of the
ureters.[1] However, this approach is still under clinical evaluation since
there is the possibility of inaccurate assessment of the stage and extent of
disease, and the adequacy and risks of such treatment have not yet been
defined.[2-5]
Because of the inaccessibility of ureteral and pelvic anatomy, accurate staging
requires pathologic analysis of the surgically excised specimen.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification to define carcinoma of the renal pelvis and ureter.[6]
TNM Definitions
Primary tumor (T)
- 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 the renal parenchyma
- T3: (For ureter only) Tumor invades beyond muscularis into periureteric fat
- T4: Tumor invades adjacent organs or through the kidney into perinephric fat
Regional lymph nodes (N)*
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension
- N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm
in greatest dimension; or multiple lymph nodes, none more than 5 cm in
greatest dimension
- N3: Metastasis in a lymph node more than 5 cm in greatest dimension
* [Note: Laterality does not affect the N classification.]
Distant metastasis (M)
- MX: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
AJCC Stage Groupings
Stage 0a
Stage 0is
Stage I
Stage II
Stage III
Stage IV
- T4, N0, M0
- Any T, N1, M0
- Any T, N2, M0
- Any T, N3, M0
- Any T, any N, M1
Patients may also be designated as having localized, regional, or metastatic
disease, 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 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 or renal
parenchyma or both but are still 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.
Regional
- 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.
Metastatic
- 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 only be determined 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 should include
the entire ureter and a margin of periureteral orifice mucosa (i.e., bladder cuff).
A TNM system for staging has been established and has demonstrated accurate
predictions of survival. The TNM staging system may be a better predictor of
prognosis than tumor grade, though both are strongly predictive of survival.
Median survival for patients with tumors confined to the subepithelial
connective tissue was 91.1 months compared to 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.[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 Jr, 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: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 329-334.
-
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]
Back to Top Treatment Option Overview
The rarity of synchronous bilateral renal pelvic neoplasia, the low incidence
of asynchronous development of contralateral upper tract tumors, and the
increased risk of tumor recurrence in the ipsilateral ureter distal to the
original pelvic tumor are the rationale for total nephroureterectomy with
bladder cuff for most patients with renal pelvic transitional cell cancers and
ureteral cancers.
Contemplation of anything less than total excision must take into account the
potential risk for tumor recurrence anywhere in the upper tract unit. In other
than unifocal, low-grade, low-stage renal pelvic tumors, the probable extensive
involvement of both contiguous and noncontiguous sites would appear to make
segmental excision an unnecessary option with a potentially serious risk.
However, an operative possibility includes segmental excision of a particular
lesion. If the extent of a tumor can be determined by intraoperative
assessment, and frozen section histologic diagnosis confirms low-grade,
unifocal tumor of limited size, then segmental excision is possible. However,
this approach should be reserved for highly selected patients. This includes
those patients who have a solitary kidney or those with decreased renal
function and who require maximal preservation of renal tissue. The likelihood
of tumor recurrence in this setting, and of extension of disease outside the
renal pelvis once the pelvis has been violated, is a serious risk that must be
heavily weighed in offering a patient this therapeutic option.
Ureteral transitional cell cancer may more readily offer the possibility of
segmental excision if the absence of proximal disease can be documented. In
this setting, attention is focused on the ease of reconstruction of the ureter
and restoration of ureterovesical continuity. This is most feasible if the
cancer is in the distal ureter. If partial ureterectomy is possible and
proximal disease has been excluded, then segmental excision and ureteral
reimplantation can be performed.
Systematic regional lymph node dissection in conjunction with
nephroureterectomy or segmental excision has not been found to enhance the
effectiveness of surgery if tumors are of high grade or high stage, since in
these instances the overall results are so poor. Correspondingly, lymph node
involvement is uncommon in low-stage disease, and lymphadenectomy is therefore
unlikely to remove additional tumor. Thus, lymph node dissection at the time
of nephrectomy may offer prognostic information, but little, if any,
therapeutic benefit.
Back to Top Localized Transitional Cell Cancer of the Renal Pelvis and Ureter
Standard treatment options:
- Nephroureterectomy with cuff of bladder.
- Segmental resection of ureter, only if the tumor is superficial and located
in the distal third of the ureter.
Treatment options under clinical evaluation:
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 employed.
Although a biopsy can be taken for staging purposes, the accuracy of this
remains to be determined. The efficacy of treatment by these maneuvers has not
been established.
- Electroresection and fulguration or laser fulguration, if the tumor is
superficial.
- Any parenchymal sparing procedure (segmental resection; ureteroscopic or
percutaneous resection/fulguration/laser destruction) if the renal unit is
solitary or renal function is depressed.
- Intrapelvic or intraureteral cytotoxic/immunotherapy. The dramatic
successes that have been reported with intravesical cytotoxic (thiotepa,
mitomycin, doxorubicin) or immunologic/inflammatory (BCG, interferon) therapy
for superficial transitional cell cancers in the bladder have 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, and the efficacy of this approach cannot be assessed, largely because
experience has been limited to those patients whose compromised clinical status
(solitary kidney, renal failure, medical risks for surgery) may have influenced
clinical outcome. The use of this approach will be limited by 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, and the adequacy and
accuracy of initial tumor staging and continued monitoring.
- Laser vaporization/coagulation. 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 at present too preliminary to assess.
Therapeutic efficacy, however, will depend on staging accuracy on initial
treatment and ease of monitoring such patients for disease recurrence and
possible progression.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized transitional cell cancer of the renal pelvis and ureter. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Back to Top Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Treatment of extensive regional disease has thus far not had well-documented
success by either radiation or systemic chemotherapy. Patients with extensive
regional disease should be considered for clinical trials.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with regional transitional cell cancer of the renal pelvis and ureter. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Back to Top Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic stratgegy. (Refer to the PDQ summary on Levels of Evidence for more information.)
The prognosis for any patient with metastatic or recurrent transitional cell
cancer is poor. The proper management of recurrence depends on the sites of
recurrence, extent of prior therapy, and individual patient considerations.
Chemotherapy regimens that have been shown effective for metastatic bladder
cancer have generally been applied to transitional cell cancers arising from
other sites. Patients with distant metastases have a poor prognosis and can
be appropriately offered treatment on a clinical trial.
In patients with metastatic or recurrent transitional cell carcinoma of the
bladder, combination chemotherapy has produced high response rates and
occasional complete responses.[1,2] Results from a randomized trial that
compared methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) to
single-agent cisplatin in advanced bladder cancer show a significant advantage
with M-VAC in both response rate and median survival. The overall response
rate with M-VAC in this cooperative group trial was 39%.[3]
Other chemotherapy agents that have shown activity in metastatic transitional
cell cancer include the following:[4-8][Level of evidence: 3iiiDiv]
- Paclitaxel.
- Ifosfamide.
- Gallium nitrate.
- Gemcitabine.
- Pemetrexed.
Ifosfamide, gallium, and pemetrexed have shown limited activity in
patients previously treated with cisplatin.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with metastatic transitional cell cancer of the renal pelvis and ureter. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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 Sr, 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 paclitaxel 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]
Back to Top Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic stratgegy. (Refer to the PDQ summary on Levels of Evidence for more information.)
The prognosis for any patient with metastatic or recurrent transitional cell
cancer is poor. The proper management of recurrence depends on the sites of
recurrence, extent of prior therapy, and individual patient considerations.
Chemotherapy regimens that have been shown effective for metastatic bladder
cancer have generally been applied to transitional cell cancers arising from
other sites. Patients with distant metastases have a poor prognosis, and can
be appropriately offered treatment on a clinical trial.
In patients with metastatic or recurrent transitional cell carcinoma of the
bladder, combination chemotherapy has produced high response rates and
occasional complete responses.[1,2] Results from a randomized trial that
compared methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) to
single-agent cisplatin in advanced bladder cancer show a significant advantage
with M-VAC in both response rate and median survival. The overall response
rate with M-VAC in this cooperative group trial was 39%.[3]
Other chemotherapy agents that have shown activity in metastatic transitional
cell cancer include the following:[4-8][Level of evidence: 3iiiDiv]
- Paclitaxel.
- Ifosfamide.
- Gallium nitrate.
- Gemcitabine.
- Pemetrexed.
Ifosfamide, gallium, and pemetrexed have shown limited activity in
patients previously treated with cisplatin.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent transitional cell cancer of the renal pelvis and ureter. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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 Sr, 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 paclitaxel 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]
Back to Top Get More Information From NCI
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Back to Top Changes to This Summary (05/22/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
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