Renal Transitional Cell Carcinoma 

Renal transitional cell carcinoma (TCC), or renal urothelial carcinoma (UC), is a malignant tumor arising from the transitional (urothelial) epithelial cells lining the urinary tract from the renal calyces to the ureteral orifice. UC is the most common tumor of the renal pelvis. Over 70,000 cases of bladder cancer are diagnosed annually in the United States. Upper urinary tract TCC is estimated to occur in 5% of all urothelial cancers and in fewer than 10% of renal tumors. Evidence indicates that the frequency of upper urinary tract malignancies is increasing.^[1]

Surgical intervention is the main form of radical treatment for localized disease. Medical therapy usually is administered as an adjuvant to surgical therapy or to patients in whom surgical treatment is contraindicated (eg, because of poor general condition or the presence of advanced disease). The role of radiation therapy in the management of upper urinary tract TCC is not well defined.

For patient education resources, see the Kidneys and Urinary System Center, as well as Blood in the Urine.

TCC accounts for more than 90% of renal pelvic tumors; other cancer types seen include squamous cell carcinoma (SCC) and adenocarcinoma. The predominant histologic pattern of UC is a papillary tumor with stratified, nonkeratinizing epithelium supported on a thin fibrovascular core.

TCC of the upper urinary tract is histologically identical to urinary bladder cancer. These 2 malignancies share the same risk factors and can occur as a part of “field cancerization,” which results from exposure of urothelium to carcinogens excreted by or activated in the urine. Hence, upper urinary tract urothelial tumors may be multifocal, and in 2-10% of cases, they are bilateral as well.

Patients with upper urinary tract urothelial tumors are at risk for the development of bladder tumors, which has an estimated incidence of 20-48%. Bladder cancer usually appears within 5 years. Patients with primary bladder cancer develop upper urinary tract UC in 2-4% of cases. The frequency of upper urinary tract UC may reach 21% in patients with bladder carcinoma in situ (CIS) and in those with certain occupational exposures.

The exact cause of upper urinary tract TCC is not known; however, several risk factors have been identified.

Workers in the chemical, petrochemical, aniline dye, and plastics industries, as well as those exposed to coal, coke, tar, and asphalt, are at increased risk for renal pelvis and ureteral tumors.

Cigarette smoking appears to be the most significant acquired risk factor for upper urinary tract UC. It is suggested that 70% of upper urinary tract urothelial tumors in men and 40% of those in women can be attributed to smoking.

Balkan endemic nephropathy, a chronic tubulointerstitial disorder, seems to be another risk factor for upper urinary tract urothelial tumors. This disease is confined to the countries that are located along the Danube River and its tributaries. Dietary exposure to aristolochic acid has been identified as a significant risk factor for Balkan nephropathy and subsequent TCC.^[2]

Analgesic abuse is a risk factor; a combination of phenacetin use and papillary necrosis results in a 20-fold increase in risk for renal urothelial tumors. Phenacetin was removed from the US market in 1983, and phenacetin-related upper urinary tract UC has become vanishingly rare.^[3]

Chronic bacterial infection with urinary calculus and obstruction may predispose to the development of urothelial cancer. SCC is the most common entity in these cases. Schistosomiasis also may predispose to SCC.

The chemotherapy drugs cyclophosphamide and ifosfamide are implicated in the development of urothelial cancers in the upper and lower urinary tract, particularly after drug-induced hemorrhagic cystitis.

United States statistics

According to American Cancer Society, an estimated 70,980 bladder cancers and 57,760 kidney cancers will be diagnosed in the United States in 2009. Primary renal pelvis and ureteric malignancies, on the other hand, are much less common; it is estimated that 2,270 renal pelvic and ureteric cancers will be diagnosed and 790 patients will die of this disease in 2009.^[4] Deaths from urothelial malignancies have been decreasing since 1995.

International statistics

Worldwide statistics vary and are inaccurate, in that renal pelvis tumors are not reported separately. The highest incidence is found in Balkan countries (eg, Bosnia, Bulgaria, Croatia, Romania, and Serbia), where UCs account for 40% of all renal cancers and are bilateral in 10% of cases.

Age-, sex-, and race-related demographics

Renal pelvis tumors rarely occur before age 40 years. The peak incidence is in the 60- to 70-year age group. Men are affected approximately 2 times as frequently as women are. The incidence is slightly higher in African Americans than in other races; reported rates are similar among white Americans, Hispanics, and Native Americans. Renal pelvic tumors are less common in Asian Americans.

Renal UC is uniformly fatal unless it is treated. In a multicenter study of 1363 patients with upper urinary tract urothelial carcinoma who were treated with radical nephroureterectomy, the 5-year cancer-specific survival probability was approximately 73%.^[5]

Tumor stage is the most important prognostic factor for upper urinary tract UC. Survival correlates closely with tumor stage. The TNM staging system developed by the International Union Against cancer (UICC) for upper urinary tract carcinomas is the most comprehensive (see Staging).

Tumor grade is another predictor of prognosis (see Histologic Findings). Tumor grade usually follows tumor stage, and patients with high-grade carcinomas have more advanced (ie, high-stage) disease. Stage and grade correlate in as many as 83% of cases, though stage remains a more accurate predictor of prognosis.

Stage T3 renal tumors have a better prognosis than ureteral tumors do. A retrospective study by Park et al found that in patients with stage pT3 disease, 5-year cancer-specific survival rates were 77.5% for renal pelvic tumors invading the renal parenchyma versus 49.7% for tumors invading peripelvic or periureteral fat; 5-year recurrence-free survival rates for the 2 tumor types were 75.6% and 32.0%, respectively.^[6] The authors suggested that the thickness of the renal parenchyma may protect against local tumor spread.

The 5-year survival rate after radical surgery depends on the disease stage, as follows:

• Stages Tis, Ta, or T1 – 91%
• Stage T2 – 43%
• Stages T3, T4, N1, or N2 – 23%
• Stages N3 or M1 – 0%

TCC may develop in the contralateral kidney after radical nephroureterectomy. In a European multicenter dataset of patients who underwent nephroureterectomy for nonmetastatic TCC, a history of bladder TCC preceding the upper urinary tract TCC was the only predictor of TCC recurrence in the contralateral upper tract.^[7] The 5-year probabilities of freedom from TCC in the contralateral upper tract TCC were as follows:

• 96.6% for patients with de novo upper-tract disease
• 91.1% for those having prior non–muscle-invasive bladder TCC
• 55.3% for those with prior muscle-invasive bladder TCC

The 5-year survival rate in selected patients after conservative surgery is reported to be 70-90%.

Recurrences in the remaining urothelium after conservative treatment are relatively frequent because of the multifocal nature of TCCs. Ipsilateral recurrence rates may reach 25-50%. Most low-grade recurrences can be treated with repeat conservative excision. The 5-year survival rates in these patients with low-grade, low-stage disease can approach 100%.

The prognosis is poor for patients with advanced SCC.