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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%. 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.
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.
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. 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.[2,3,4,5]
Because of the inaccessibility of ureteral and pelvic anatomy, accurate staging requires pathologic analysis of the surgically excised specimen.
Definitions of TNM
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define carcinoma of the renal pelvis and ureter.
Patients may also be designated as having localized, regional, or metastatic disease, as follows:
Patients with localized disease may be classified into three groups:
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]
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.
Standard treatment options:
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.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials 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.
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.
Check for U.S. clinical trials from NCI's list of cancer clinical trials 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.
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 strategy. (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%.
Other chemotherapy agents that have shown activity in metastatic transitional cell cancer include the following:[4,5,6,7,8][Level of evidence: 3iiiDiv]
Ifosfamide, gallium, and pemetrexed have shown limited activity in patients previously treated with cisplatin.
Check for U.S. clinical trials from NCI's list of cancer clinical trials 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.
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.
Ifosfamide, gallium, and pemetrexed have shown limited activity in patients previously treated with cisplatin.
Check for U.S. clinical trials from NCI's list of cancer clinical trials 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.
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.
Stage Information for Transitional Cell Cancer of the Renal Pelvis and Ureter
Updated staging information for 2010 (cited Edge et al. as reference 6).
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 who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment is:
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Levels of Evidence
Some of the reference citations in this 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.
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National Cancer Institute: PDQ® Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/transitionalcell/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2011-11-18
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