Ureteral Cancer: Symptoms, Types, Causes and Treatment

Ureteral cancer, though rare, can have a profound impact on health and wellbeing. Early recognition, understanding the various types, identifying causes, and knowing the latest treatments are crucial for improving outcomes. This comprehensive guide draws on the latest research to provide a clear, evidence-based overview of ureteral cancer.

Symptoms of Ureteral Cancer

When it comes to ureteral cancer, the symptoms can be subtle at first but may become increasingly disruptive as the disease progresses. Detecting these signs early can lead to a faster diagnosis and better prognosis, but awareness remains a challenge due to the rarity of the condition.

Symptom	Description	Frequency/Impact	Source(s)
Hematuria	Blood in urine (visible/invisible)	Most common symptom	1 3 2
Flank Pain	Pain in side/back near kidneys	Frequent, sometimes severe	1 3
Dysuria	Painful or difficult urination	Occasional	1
Urinary Frequency	Need to urinate more often	Can accompany dysuria	1
Obstructive Symptoms	Blockage, hydronephrosis, possible infection	In advanced cases	3 2 5
Abdominal Symptoms	Pain, nausea, vomiting	Rare, may indicate advanced/metastatic disease	2 3
Bone Pain	Pain in bones due to metastasis	Rare, advanced disease	3

Table 1: Key Symptoms

Hematuria: The Most Telling Sign

• Hematuria—blood in the urine—is the most common and often the first symptom people notice. It can be either visible (gross hematuria) or microscopic, detected only by laboratory testing. Although painless, its presence should prompt further medical evaluation, especially in older adults or those with risk factors for urinary tract cancers 1 3 2.

Pain and Urinary Changes

• Flank pain arises when a tumor blocks the ureter, leading to a backup of urine (hydronephrosis) and pressure on the kidney. This pain can be dull or severe and is sometimes mistaken for kidney stones or infection 1 3.
• Dysuria and urinary frequency may occur, though these are less common than hematuria. They typically indicate irritation or partial obstruction of the urinary tract 1.

Symptoms of Advanced Disease

• As the cancer progresses, the tumor can cause obstructive symptoms such as severe hydronephrosis, urinary retention, or even infection. In rare cases, metastatic spread can lead to bone pain, or abdominal symptoms such as nausea, vomiting, or bowel obstruction if adjacent organs are affected 2 3.
• For example, one patient presented with heel pain due to bone metastasis as the first sign of ureteral cancer, illustrating how the disease can masquerade as other conditions 3.

Types of Ureteral Cancer

Ureteral cancer is not a single disease but rather a group of malignancies that can arise from different cell types and exhibit various behaviors. Understanding the types is essential for guiding treatment and estimating prognosis.

Type	Description/Features	Aggressiveness/Prognosis	Source(s)
Urothelial (Transitional Cell) Carcinoma	Most common (>90%); arises from urothelial lining	Varies; depends on grade/stage	1 5 8
Squamous Cell Carcinoma	Rare; associated with chronic irritation/infection	Aggressive, poorer prognosis	9
Adenocarcinoma	Very rare; glandular origin	Variable	9
Variant Urothelial Subtypes (e.g., Plasmacytoid, Papillary)	Rare, may behave aggressively	Prognosis varies by subtype	2 7 6
Lymphoma	Extremely rare; from lymphoid tissue	Prognosis depends on lymphoma type	9

Table 2: Major Types of Ureteral Cancer

Urothelial (Transitional Cell) Carcinoma

• By far the majority of ureteral cancers are urothelial carcinomas, formerly known as transitional cell carcinomas. They arise from the urothelial lining that coats the inside of the urinary tract 1 5 8.
• These can be classified further by their appearance (e.g., papillary vs. non-papillary) and grade, both of which influence the course of disease and response to treatment 7.

Rare and Variant Types

• Squamous cell carcinoma and adenocarcinoma are much less common forms, associated with chronic irritation or infection and carry a worse prognosis 9.
• Variant histological subtypes of urothelial carcinoma—such as plasmacytoid, micropapillary, and sarcomatoid—are rare but often more aggressive and challenging to treat 2 6 7.
  • For example, plasmacytoid urothelial carcinoma is highly aggressive, with frequent metastasis and poor outcomes 2.
• Lymphoma of the ureter is a medical rarity, requiring specialized diagnostic and therapeutic approaches 9.

Prognostic Implications of Type

• The histological subtype significantly impacts prognosis and response to therapy. Papillary urothelial carcinomas tend to have a better prognosis compared to atypical or variant subtypes 7.
• The stage at diagnosis (how far the cancer has spread) is also a critical determinant of survival, regardless of type 4.

Causes of Ureteral Cancer

Why do some people develop ureteral cancer when most do not? Several risk factors—both environmental and genetic—are known to play roles in the development of this uncommon malignancy.

Cause/Risk Factor	Mechanism or Association	Prevalence/Impact	Source(s)
Tobacco Use	Carcinogen exposure damages urothelium	Major risk factor	5 8
Occupational Carcinogens	Aromatic amines (dyes, chemicals)	Significant in some jobs	5 8
Analgesic Abuse	Phenacetin, NSAIDs	Historically important	5 8
Chronic Irritation	Stones, infections	Linked to squamous/adenocarcinoma	5 9
Balkan Endemic Nephropathy, Chinese Herb Nephropathy	Environmental nephrotoxins	Regional importance	8
Genetic Factors	SULT gene polymorphisms	Alters individual susceptibility	8
Bladder/Urinary Tract Cancer History	Field cancerization	20–50% coexistence	5

Table 3: Causes and Risk Factors for Ureteral Cancer

Environmental and Lifestyle Risks

• Tobacco use is the single most important risk factor, as carcinogens in smoke are excreted in urine and directly contact the urothelium 5 8.
• Occupational exposures—particularly to aromatic amines found in dyes, rubber, and chemical industries—increase risk, echoing patterns seen in bladder cancer 5 8.
• Prolonged analgesic (painkiller) abuse, especially with phenacetin (no longer widely used), historically led to increased risk. NSAIDs are under investigation, but the link is less clear today 5 8.
• Chronic irritation from kidney stones, long-term infections, or indwelling catheters is associated with non-urothelial types like squamous cell carcinoma and adenocarcinoma 5 9.

Geographic and Genetic Factors

• Certain regions, such as the Balkans, report higher rates of upper urinary tract cancers due to environmental nephrotoxins (Balkan endemic nephropathy, Chinese herb nephropathy) 8.
• Genetic polymorphisms, especially involving the SULT gene, may increase susceptibility to environmental carcinogens and thus to ureteral cancer in predisposed individuals 8.

Relationship to Other Urinary Tract Cancers

• There is a notable association with bladder cancer: up to half of people with upper tract urothelial cancer (including ureteral tumors) will have bladder cancer at some point, supporting the idea of “field cancerization” where the entire urothelium is at risk 5.

Treatment of Ureteral Cancer

Treatment strategies for ureteral cancer have evolved rapidly, offering a range of options from surgery to cutting-edge molecular therapies. The choice of approach is influenced by the cancer’s type, stage, location, and patient factors.

Treatment	Indication/Use Case	Outcomes/Considerations	Source(s)
Nephroureterectomy (NUE)	Standard for high-risk/advanced disease	Mainstay, controls local disease	5 13 11
Segmental Ureterectomy	Selected low-risk, distal tumors	Preserves kidney, risk of recurrence	13 11
Endoscopic/Conservative	Low-grade, localized tumors	Organ-sparing, requires surveillance	5 11
Chemotherapy	Advanced/metastatic, high-grade tumors	Variable benefit, based on histology/stage	7 5 3
Radiation Therapy	Palliative or symptom control	Limited efficacy	5 3
Lymphadenectomy	Upper/middle ureteral cancer (selected)	Reduces recurrence, improves survival	12
Targeted/Immunotherapy	Advanced, select cases	Emerging, based on molecular profile	10 6

Table 4: Main Treatments for Ureteral Cancer

Surgery: The Mainstay

• Radical nephroureterectomy (NUE)—removal of kidney, ureter, and a cuff of bladder—is the standard treatment for most high-risk or invasive ureteral cancers 5 13.
• Segmental ureterectomy or conservative surgery may be used for superficial, low-grade tumors, especially in the lower ureter, to preserve kidney function 13 11. These approaches require careful selection and close post-operative surveillance due to risk of recurrence.
• Endoscopic treatments (ureteroscopic or percutaneous) are increasingly used for small, low-grade tumors, particularly in patients with limited kidney function or high surgical risk 5 11.

Systemic and Adjunctive Therapies

• Chemotherapy is important for advanced or metastatic disease, and its benefit varies with histological subtype and tumor stage. It is more effective in high-stage disease (T3/T4) and for non-papillary subtypes, but may not benefit early-stage or papillary tumors 7 5 3.
• Radiation therapy is used mainly for symptom relief in advanced cases, as it does not significantly improve survival 5 3.
• Lymphadenectomy (removal of regional lymph nodes) may improve outcomes for upper/middle ureteral tumors, but its role is less clear for lower ureter cancers 12.

Emerging and Personalized Treatments

• Molecular profiling and immunotherapy are promising new areas. For select cases, especially those with advanced or variant urothelial carcinomas, targeted therapies and immune checkpoint inhibitors may offer hope, although evidence is still emerging 10 6.
• Pathology-driven therapy is increasingly relevant, with choices guided by tumor type, grade, molecular markers, and patient-specific factors 10 6 7.

Prognosis and Follow-Up

• Prognosis depends heavily on stage and grade at diagnosis. Early-stage, low-grade tumors have excellent outcomes with surgery alone, while more advanced cancers carry a higher risk of recurrence and metastasis 4 5.
• Close surveillance is essential after treatment, particularly for patients managed conservatively or those with high-risk features 11 13.

Conclusion

Ureteral cancer, though rare, poses significant diagnostic and therapeutic challenges. Prompt recognition of symptoms, an understanding of the diverse types and risk factors, and a tailored, multidisciplinary approach to treatment are key to optimizing outcomes.

Key Takeaways:

• Hematuria and flank pain are the most common presenting symptoms; unusual symptoms may indicate advanced disease 1 3.
• Urothelial carcinoma is the predominant type; rare subtypes and non-urothelial cancers require special consideration 1 2 6 7.
• Tobacco use, occupational exposure, and prior urinary tract cancers are major risk factors; genetic and geographic factors can also play roles 5 8.
• Radical nephroureterectomy remains the gold standard for most cases, while conservative and endoscopic treatments are suitable for select patients 5 13 11.
• Chemotherapy, lymphadenectomy, and emerging therapies play important roles in advanced disease, with outcomes influenced by tumor type and stage 7 12 10.
• Multidisciplinary care and careful follow-up are essential for best results and improved quality of life.

By staying informed and vigilant, patients and clinicians alike can better navigate the complexities of ureteral cancer and achieve the best possible outcomes.