Renal pelvis cancer and ureteral cancer are collectively referred to as upper urinary tract tumors.
Epidemiology and Risk Factors
The incidence is relatively low, accounting for approximately 5%–10% of urothelial tumors. The age group with the highest prevalence is 70–90 years. Tumors involving the lower ureter are more common than those in the upper ureter. Risk factors include smoking, long-term use of analgesics, cyclophosphamide, and medications containing aristolochic acid. Chronic infections, long-term irritation from stones, and occupational exposure to substances such as aniline and arsenic also increase the risk of developing upper urinary tract tumors.
Pathology
Over 90% of upper urinary tract tumors are urothelial carcinomas, specifically upper tract urothelial carcinoma (UTUC). Other types include squamous cell carcinoma and adenocarcinoma. The histological grading and growth patterns of these tumors are similar to those of bladder cancer. The tumor may spread along the renal pelvis mucosa, retrogradely invading the renal collecting ducts, and potentially infiltrating the renal parenchyma or surrounding tissues. It may also extend anterogradely to involve the distal ureter. Since the muscle layers of the renal pelvis and ureter are relatively thin, invasion into the muscle layer occurs early. The adventitial tissue contains abundant blood vessels and lymphatic vessels, leading to early lymphatic metastasis that often involves the renal hilum, aortic, inferior vena cava, ipsilateral common iliac, and pelvic lymph nodes. Hematogenous metastasis commonly occurs in bones, lungs, and the liver.
Clinical Manifestations
The most common symptom is intermittent, painless gross hematuria or microscopic hematuria, and occasionally, strip-like blood clots may be observed. Approximately 20% of patients experience dull pain in the lumbar region, which is primarily caused by tumor invasion leading to upper urinary tract obstruction and resulting hydronephrosis. In some cases, blood clots obstructing the ureter can cause renal colic. Advanced-stage disease may present with a palpable mass in the lumbar or abdominal region, weight loss, anemia, lower extremity edema, or bone pain. Signs of renal pelvis cancer and ureteral cancer are often nonspecific, and some cases are incidentally detected during physical examination or imaging studies.
Diagnosis
In middle-aged and elderly patients with painless intermittent hematuria, renal pelvis or ureteral cancer should be considered in addition to bladder cancer. Diagnosis requires further confirmation with imaging, ureteroscopy, urinary cytology, and tumor marker testing.
Urinary Cytology and Tumor Marker Testing
Urinary exfoliative cytology, fluorescence in situ hybridization (FISH), and urinary DNA methylation tests are commonly used noninvasive methods to diagnose urothelial tumors. Positive results suggest the presence of a urothelial tumor. If bladder and urethral tumors are excluded through cystoscopy, renal pelvis or ureteral cancer should be considered.
Imaging Studies
Ultrasound examination is a screening method for hematuria and can detect space-occupying lesions in the renal pelvis or ureters, as well as upstream dilation or hydronephrosis.
Intravenous urography is a conventional diagnostic method for renal pelvis and ureteral cancer. It can reveal filling defects, obstruction, or hydronephrosis in the affected region. Severe obstruction resulting in significant decreases in renal function may cause the collecting system to appear nonvisualized.
Computed tomography urography (CTU) is the primary technique for diagnosing renal pelvis and ureteral cancer. Findings include filling defects, wall thickening, or obstruction in the calyx, renal pelvis, or ureter. However, CTU may struggle to detect flat lesions. CTU can simultaneously evaluate tumor location, invasion depth, relationships to surrounding organs, and lymph node involvement. For patients unable to undergo CT scans, magnetic resonance urography (MRU) provides diagnostic efficacy similar to CTU.
Ureteroscopy or Flexible Ureteroscopy with Biopsy
Ureteroscopy directly visualizes tumors in the ureter or renal pelvis. Flexible ureteroscopy allows access to each calyx and facilitates biopsies of suspicious lesions for definitive diagnosis.
Retrograde Pyelography via Cystoscopy
Retrograde pyelography can be used to identify tumor location and the degree of hydronephrosis. The procedure can also collect urine samples or washings from the renal pelvis for cytology analysis. Cystoscopy findings may sometimes include blood emanating from the affected ureteral orifice or concurrently existing bladder tumors, as approximately 17% of renal pelvis and ureteral cancers coexist with bladder cancer.
Differential Diagnosis
Renal pelvis cancer should be differentiated from renal cancer, blood clots or necrotic tissue in the renal pelvis, while ureteral cancer needs to be distinguished from ureteral strictures, stones, or polyps. Imaging studies, urinary exfoliative cytology, FISH, and tumor marker tests can assist in the differential diagnosis.
Renal Cancer
When renal pelvis cancer invades the renal parenchyma, differentiation from renal cancer is often necessary. Clinically, renal pelvis cancer typically presents with gross hematuria earlier. On imaging, renal cancer on CT is often seen as a round or ovoid mass, frequently with a pseudocapsule, and shows a hypervascular pattern of "rapid enhancement and washout" on contrast-enhanced scans. Biologically, renal pelvis cancer is more prone to lymph node metastasis, while renal vein or inferior vena cava tumor thrombi are more commonly seen in renal cancer.
Blood Clots and Necrotic Tissue in the Renal Pelvis
On non-contrast imaging, these may resemble renal pelvis cancer, but contrast-enhanced CT or MRI shows no enhancement.
Ureteral Strictures or Stones
These conditions usually have a history of stones, infection, or surgery and manifest as varying degrees of upper urinary tract obstruction and hydronephrosis. Intravenous pyelography, CT urography (CTU), retrograde pyelography, or ureteroscopy can typically aid in differentiation.
Ureteral Polyps
These are rare benign tumors, often secondary to stones. Primary ureteral polyps often appear as long segments of polyps and usually do not cause hydronephrosis. Ureteroscopy and biopsy can confirm the location, number, and nature of the lesions.
Treatment
Radical Nephroureterectomy
This is the standard surgical approach for renal pelvis and ureteral cancer. Since urothelial carcinoma often originates multicentrically and spreads along the urinary tract, complete removal of the affected kidney and the entire length of the ureter, including the portion of the bladder wall surrounding the ureteral orifice, is needed. In recent years, minimally invasive approaches such as laparoscopic and robot-assisted laparoscopic techniques have been commonly used. Postoperative intravesical instillation of chemotherapeutic agents can reduce the incidence of bladder tumors.
Nephron-Sparing Surgery
For small, well-differentiated, non-invasive pedunculated papillary tumors, particularly in cases of solitary kidney or impaired contralateral renal function due to renal pelvis or upper ureteral cancer, endoscopic resection or laser ablation via ureteroscopy can be performed. For lower ureteral tumors, segmental resection of the tumor and distal ureter with subsequent ureteral reimplantation into the bladder may be conducted.
Comprehensive Treatment
For advanced renal pelvis and ureteral cancer, comprehensive treatments are required. Neoadjuvant chemotherapy before surgery or adjuvant chemotherapy or radiotherapy following surgical resection may be utilized. Systemic chemotherapy is the main treatment for advanced cases. In recent years, immunotherapy and antibody-drug conjugates have shown good efficacy in treating urothelial carcinoma. Combining immunotherapy with chemotherapy or antibody-drug conjugates offers the potential to further enhance treatment outcomes.
Prognosis
The prognosis of renal pelvis and ureteral cancers primarily depends on the tumor stage and pathological grade. The 5-year cancer-specific survival rate is approximately 86% for non-muscle-invasive tumors, 70% for muscle-invasive organ-confined tumors, and 44% for locally advanced tumors. Additionally, the incidence of bladder cancer after surgery for renal pelvis and ureteral cancers is around 20%–50%.