TUMORS OF THE RENAL PELVIS AND URETER
A vast majority of the tumors that originate in the renal pelvis and ureter develop from urothelial cells, which line the renal calices, ureters, and bladder. Urothelial carcinomas (also known as transitional cell carcinomas) of the upper urinary tract represent less than 10% of all renal tumors and only 5% of all urothelial carcinomas.
Approximately 5% of ureteral tumors are in the
proximal ureter, 25% are in the midureter, and 70% are in the distal ureter.
Moreover, patients with an upper tract tumor are much more likely to develop a
bladder tumor than vice versa. The reason for this apparent downstream effect
is not clear; however, it has been hypothesized to reflect downstream seeding or
longer exposure of bladder urothelium to carcinogens.
RISK FACTORS AND RADIOGRAPHIC APPEARANCE OF TUMORS OF THE RENAL PELVIS AND URETER
RISK FACTORS
Upper tract urothelial carcinomas tumors occur on
average in the seventh decade. Men and Caucasians are twice as likely to
develop these tumors as women and African Americans.
Several genetic and environmental risk factors are
known. Many are shared with urothelial carcinoma of the bladder, including
cigarette smoking, aromatic amine (e.g., aniline) exposure, cyclophosphamide
exposure, and mutations in certain genes (e.g., TP53 and RB).
Other factors, however, appear to increase the risk of upper tract carcinomas in particular. Phenacetin
abuse, for example, has been associated not only with analgesic nephropathy
(see Plate 4-30) but also with upper tract urothelial carcinomas. In addition,
the interstitial nephropathy known as Balkan nephropathy (seen primarily in
populations near the Danube River and its tributaries) increases the risk of
upper tract urothelial carcinomas. Finally, hereditary nonpolyposis colorectal
cancer (HNPCC, or Lynch syndrome) is an autosomal dominant condition
characterized by altered DNA mismatch repair genes (MLH1, MSH2, MSH6)
and increased risk of cancer in the stomach, small intestine, colon, liver,
endometrium, ovary, and upper urinary tract (urothelial type).
PRESENTATION AND DIAGNOSIS
The major presenting symptom of an upper tract
urothelial carcinoma is gross or microscopic hematuria. If there is obstruction
of the ureter, dull flank pain may also occur.
Patients suspected of having upper tract malignancies
should be evaluated using contrast-enhanced CT, which may reveal a visible mass
or filling defect on delayed urographic phase. If there is a chronic obstruction
to urine outflow, dilation of the renal pelvis and ureter may be seen, depending
on the level of the mass.
The presence of regional extension or metastases may
also be assessed using various radiographic modalities. Urothelial carcinomas
of the upper tract, like those of the bladder, may metastasize to lymph nodes,
liver, lung, and bone. CT can be used to assess for the presence of abdominal
or pelvic metastases. Chest radio- graph is often adequate to screen for the
presence of lung metastases. A bone scan may be performed to evaluate for bone
metastases in the setting of suggestive symptoms or elevated serum alkaline phosphatase concentration.
Once the presence of an upper tract tumor has been
established, cystoureteroscopy should be performed to examine the entire urine
collecting system. A retro-grade pyeloureterogram performed during this
procedure often reveals a filling defect in the area of the tumor. All
abnormal-appearing areas should undergo directed biopsy. The histopathologic
findings of upper tract urothelial carcinomas are similar to those of the lower tract and are classified in a similar manner.
Once the tumor has been radiographically and pathologically characterized,
initial staging can be performed according to TNM criteria.
APPEARANCE
(URETEROSCOPIC, GROSS, AND MICROSCOPIC) AND STAGING OF TUMORS OF THE RENAL PELVIS AND URETER
TREATMENT
Surgery is the therapy for localized disease. The
optimal approach depends on characteristics of both the patient and tumor.
For a patient with a normally functioning contralateral kidney, the
gold-standard treatment is radical nephroureterectomy, in which the entire
kidney and ureter on the affected side are removed, along with a cuff of
normal-appearing bladder. Removal of the entire urothelial tract is essential
because there is a high risk of recurrent disease if a ureteral stump is left
behind.
Radical nephroureterectomy can be performed from
either an open or laparoscopic approach. Regional lymphadenectomy is usually
performed simultaneously. For proximal tumors, the ipsilateral renal hilar,
para-aortic, and
paracaval nodes are removed; for distal tumors, the ipsilateral pelvic lymph
node chains are removed. The main benefit to lymph node dissection is more
accurate staging of the tumor, which may provide prognostic information and
determine eligibility for trials of adjuvant chemotherapy. There is no evidence,
however, that there is any survival benefit to lymphadenectomy itself because
patients with node-positive disease often have distant metastasis at the time
of node dissection.
For a patient with a small, localized, low-grade
tumor, or with a relative contraindication to nephroureterectomy (solitary
functional kidney, bilateral upper tract tumors, chronic kidney disease, severe
comorbid illness), a nephron-sparing approach may be used instead. In most
cases, the tumor is accessed using retrograde ureteroscopy. After initial
debulking with a basket, forceps, or other device, the tumor is ablated using a
laser or monopolar electrocautery. If the tumor cannot be adequately treated
from a retrograde approach, a percutaneous anterograde approach using a nephroscope
may be undertaken.
For a patient with a tumor confined to the distal
ureter, selective distal ureterectomy with ureter reimplantation may be an
option if there is a relative contraindication to nephroureterectomy (see
previous list) or the tumor is small and low grade.
Systemic chemotherapy may be administered either
before surgery (neoadjuvant) or after extirpation (adjuvant). Because
urothelial carcinomas of the upper tract are relatively rare, however, there
are no randomized controlled trials that substantiate the benefit of chemotherapy in patients with advanced or metastatic lesions. Nonetheless, in
patients with known metastasis, chemotherapy regimens are typically employed
and are similar to those used for urothelial carcinomas of the bladder (i.e.,
cisplatin-based). In general, however, patients with metastatic upper tract
tumors have a poor outcome no matter the treatment strategy.
PROGNOSIS
Tumor stage and grade are critical factors when determining an individual patient’s prognosis. Following radical nephroureterectomy,
one series noted 5-year disease-specific survival rates of 100% with Ta/Tis
disease, 92% with T1 disease, 73% for T2 disease, 40% for T3 disease, and 0%
for T4 disease. Another series noted 5-year disease-specific survival rates of
94% with Ta/Tis disease, 91% with T1 disease, 75% with T2 disease, 54% with T3
disease, and 12% with T4 disease. In addition, this series found 5-year
disease-specific survival rates to be 89% with low-grade disease and 63% with
high-grade disease. The type of surgical intervention also affects outcomes because a higher risk of recurrence
has been observed among those treated using an endourologic approach.
FOLLOW-UP
A significant subset of the patients treated for
urothelial carcinoma of the upper tract will subsequently develop bladder cancer. Thus it is essential to perform
surveillance of all patients with regular examination, cytoscopy, urine cytology,
and CT of the abdomen and pelvis for several years after initial treatment. In
patients who have undergone nephron-sparing treatment, surveillance
ureteroscopy is often indicated as well.
