Ureteral Cancer

Urine cytology and molecular urine markers

• Voided urine cytology detects malignant urothelial cells shed from the tumor surface and has the highest sensitivity for high-grade lesions. Selective upper tract urine cytology — collected through a catheter passed into the ureter or renal pelvis during ureteroscopy — improves diagnostic yield when localized upper tract disease is suspected. Emerging urinary biomarker tests offer additional diagnostic information but have not yet replaced cytology in routine clinical practice.

CT urogram (CTU)

• Multiphase CT with intravenous contrast, including a dedicated urographic phase, is the primary imaging study for suspected ureteral cancer. It provides high-resolution visualization of the entire urothelial tract, allowing characterization of filling defects, assessment of wall thickening, and evaluation of the degree of proximal ureteral and renal pelvic dilation. Concurrent thoracic imaging is performed for staging purposes to assess for pulmonary metastases.

Ureteroscopy and biopsy

• Flexible or rigid ureteroscopy allows direct endoscopic visualization of the ureteral lumen and targeted biopsy of suspicious lesions. The histopathological result establishes the tissue diagnosis and, critically, determines tumor grade — which is one of the most important factors in selecting between radical and kidney-sparing management strategies. Concurrent cystoscopic examination of the bladder is performed at the same setting to assess for synchronous urothelial tumors.

Ureteral cancer is staged using the AJCC TNM system.

Stage 0

• indicates non-invasive tumor or carcinoma in situ confined to the urothelial surface

Stage I

• describes invasion into the lamina propria — the connective tissue layer beneath the surface epithelium

Stage II

• indicates invasion into the muscularis layer of the ureter wall

Stage III

• encompasses invasion into the periureteric fat or extension into adjacent structures including the kidney or renal pelvis

Stage IV

• applies when regional lymph nodes are involved or when the cancer has spread to distant organs

Tumor grade — whether cells appear low-grade or high-grade under microscopic examination — is an independent prognostic factor of equal importance to pathological stage in guiding treatment decisions.

Radical nephroureterectomy

• Radical nephroureterectomy (RNU) — surgical removal of the kidney, the entire ipsilateral ureter, and a cuff of bladder tissue surrounding the ureteral orifice — is the standard of care for high-grade, muscle-invasive, or multifocal ureteral cancers. Complete excision of the bladder cuff is oncologically essential, as incompletely excised ureteral stumps carry a substantial risk of local recurrence. Minimally invasive techniques — laparoscopic or robotic RNU — have become the preferred surgical approach at experienced centers, achieving equivalent cancer control outcomes while offering reduced intraoperative blood loss and faster postoperative recovery. 

Kidney-sparing surgery

• Nephron-sparing management is considered when preservation of renal function is clinically imperative — most commonly in patients with a solitary kidney, bilateral tumors, pre-existing chronic kidney disease that would render the patient dialysis-dependent after nephrectomy, or low-grade, unifocal tumors amenable to complete endoscopic treatment. Endoscopic laser ablation through the ureteroscope, or segmental ureterectomy with ureteral reimplantation, may be appropriate in carefully selected cases. The trade-off is a higher rate of local recurrence, necessitating more intensive endoscopic surveillance.

Perioperative chemotherapy

• Cisplatin-based combination chemotherapy administered before surgery (neoadjuvant chemotherapy) is now recommended for patients with high-grade or locally advanced disease, as emerging data suggest a survival benefit when full-dose cisplatin can be delivered with intact bilateral renal function — a window that is lost after nephrectomy when the GFR invariably falls. Adjuvant chemotherapy after RNU is considered for patients with positive lymph nodes or adverse pathological features, though evidence remains less robust than for the neoadjuvant setting.
• Intravesical instillation of chemotherapy (gemcitabine or mitomycin-C) directly into the bladder at the time of or immediately following RNU is standard practice and is supported by randomized trial evidence demonstrating a reduction in the rate of early intravesical recurrence.

Immunotherapy

• For locally advanced or metastatic urothelial carcinoma, immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway — including pembrolizumab, nivolumab, and avelumab — are established treatment options for patients who are ineligible for platinum-based chemotherapy or who progress after platinum-based regimens.