Ureter Cancer

The ureters are tubes that carry urine from the kidneys to the bladder.

Ureter cancer is relatively uncommon. Most tumors arise from urothelial cells lining the ureter and are therefore classified as urothelial carcinoma. Squamous cell carcinoma, adenocarcinoma, and other histologic types are much less common.

Cancers of the renal pelvis and ureter are commonly grouped together as upper tract urothelial carcinoma (UTUC) because they share many risk factors, pathologic features, and systemic treatment approaches.

Treatment depends not only on tumor location but also on grade, depth of invasion, whether the disease is multifocal, and whether lymph nodes or distant organs are involved.

The exact cause of ureter cancer is often unknown, but several risk factors are well established.

These include:

Smoking、Long-term occupational exposure to aromatic amines and other carcinogenic chemicals、Exposure to aristolochic acid、Certain chronic inflammatory or stone-related conditions of the upper urinary tract、A personal history of bladder cancer or other urothelial cancers、Lynch syndrome and other inherited cancer-predisposition conditions、Certain endemic kidney diseases associated with aristolochic acid exposure.Smoking is one of the most important modifiable risk factors.

Blood in the urine is the most common symptom of ureter cancer. It may be visible to the eye or detected only on a urine test.

Hematuria can come and go, so temporary disappearance of blood does not necessarily mean the underlying condition has resolved.

Other possible symptoms include:Flank or back pain、Renal colic、Hydronephrosis、Urinary discomfort、Fatigue、Loss of appetite、Unexplained weight loss.

Flank pain or hydronephrosis may occur when the tumor blocks the flow of urine.Some patients have no symptoms and are diagnosed incidentally on imaging.

Evaluation of suspected ureter cancer usually combines imaging, cystoscopy, urine cytology, and ureteroscopy when needed.

CT urography is one of the most important imaging tests for UTUC. It can help identify the location and extent of the tumor, urinary obstruction, local invasion, lymph node involvement, and distant spread.

MRI-based urinary tract imaging may be used when contrast-enhanced CT is not appropriate.

Urine cytology may detect abnormal urothelial cells and is particularly useful in higher-grade disease, although a negative result does not rule out cancer.

Cystoscopy is also commonly performed because patients with UTUC have an increased risk of synchronous or subsequent bladder cancer.

When imaging and cytology do not provide enough information, ureteroscopy may be used to directly visualize the tumor and obtain a biopsy for pathologic diagnosis and grading.

Risk Stratification

Not every patient with UTUC needs immediate removal of the kidney and ureter.

Doctors estimate whether the disease is low or high risk based on factors such as tumor size and number, pathologic grade, imaging evidence of invasion, hydronephrosis, and urine cytology.

Low-risk tumors are generally localized, low grade, and lack clear invasive features. Kidney-sparing treatment may be preferred in these patients.

High-grade tumors, invasive features on imaging, larger tumors, or multifocal disease generally require more intensive treatment.

Current EAU guidance recommends kidney-sparing management as the primary option for low-risk UTUC and radical nephroureterectomy for high-risk nonmetastatic disease.

Low-Risk UTUC

For low-risk UTUC, preserving the kidney is now preferred whenever oncologically appropriate.

Treatment may include ureteroscopic removal or laser ablation of the tumor. Selected low-risk tumors in the distal ureter may also be treated with segmental ureterectomy.

Close surveillance is essential after endoscopic treatment. Current EAU guidance also recommends considering a second-look ureteroscopy within about eight weeks after initial endoscopic management.

High-Risk UTUC

For high-risk UTUC without distant metastases, radical nephroureterectomy remains the standard treatment.

The procedure generally removes the affected kidney, the entire ureter, and a small cuff of bladder tissue around the ureteral opening.

Open, laparoscopic, and robot-assisted approaches may all be used depending on the clinical situation. For selected high-risk patients, template-based regional lymph node dissection may also be considered.

Selected high-risk tumors confined to the distal ureter may sometimes be managed with distal ureterectomy to preserve kidney function.

Perioperative Systemic Therapy

Perioperative systemic treatment may be considered for selected patients with high-risk UTUC.

Cisplatin-based chemotherapy before surgery can be considered in some patients. One reason is that kidney function may decline after nephroureterectomy, making cisplatin treatment more difficult afterward.

After radical nephroureterectomy, current EAU guidance recommends adjuvant platinum-based chemotherapy for eligible patients with pathologic stage pT2–T4 and/or lymph node-positive disease.

Adjuvant immunotherapy may also be considered in selected high-risk patients who are not candidates for or decline platinum-based chemotherapy, depending on biomarker status, treatment history, and local approvals.

Postoperative Bladder Instillation

Bladder recurrence is an important issue after treatment for UTUC.

For patients without a previous history of bladder cancer, current EAU guidance recommends a single postoperative intravesical chemotherapy instillation after radical nephroureterectomy to reduce the risk of subsequent bladder tumors.

Locally Advanced or Metastatic Ureteral Cancer

The statement that chemotherapy and radiation are generally ineffective is no longer accurate.

Advanced ureteral urothelial cancer is treated using systemic strategies similar to those used for advanced urothelial bladder cancer.

Enfortumab vedotin plus pembrolizumab is now an important first-line treatment for advanced or metastatic urothelial carcinoma. About one-quarter of patients in the EV-302 trial had UTUC, and the benefit was seen regardless of primary tumor location.

When this combination is not appropriate or available, platinum-based chemotherapy remains an important option. Cisplatin-based combination chemotherapy may be used in eligible patients, while gemcitabine plus carboplatin can be considered when cisplatin is not suitable.

Patients whose cancer does not progress after first-line platinum chemotherapy may be candidates for maintenance avelumab.

Molecular Testing and Targeted Therapy

Molecular testing should be considered early in advanced or metastatic UTUC.

FGFR2 and FGFR3 alterations are particularly relevant, and FGFR3 alterations are relatively common in upper tract disease.

For selected previously treated patients with susceptible FGFR2/3 alterations, the FGFR inhibitor erdafitinib may be an option. Current EAU guidance recommends considering early FGFR testing in advanced or metastatic UTUC.