Papillary urothelial carcinoma

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
June 11, 2025

Papillary urothelial carcinoma is a type of cancer that develops from specialized cells lining the inside of the urinary tract. The urinary tract includes the kidneys, ureters, bladder, and urethra. Most tumours occur in the bladder, but this type of cancer can arise anywhere along the urinary tract. The tumour is called papillary because it grows in finger-like projections extending from the inner surface of the urinary tract.

Pathologists classify this cancer into two main categories: non-invasive and invasive. Non-invasive tumours remain within the surface lining (urothelium), while invasive tumours grow into deeper layers of tissue. Determining whether the tumour is invasive is critical because non-invasive tumours typically are curable by surgery alone, whereas invasive tumours usually require additional treatments beyond surgery.

Understanding the urinary tract

The urinary tract is designed to remove waste and excess water from the body through urine. It is composed of the following parts:

• Kidneys: Two organs that filter blood to form urine.

• Ureters: Tubes that carry urine from the kidneys to the bladder.

• Bladder: A muscular organ that stores urine until urination occurs.

• Urethra: A tube through which urine exits the body.

The inner surface of the urinary tract is covered by a specialized lining of urothelial cells, forming a protective barrier called the urothelium.

What are the symptoms of papillary urothelial carcinoma?

Common symptoms of papillary urothelial carcinoma include:

• Blood in the urine (hematuria), causing urine to appear pink, red, or brown.

• Pain or burning sensation during urination (dysuria).

• Frequent or urgent urination.

• Lower abdominal discomfort or pain.

Symptoms can vary among individuals, and some may initially experience very mild or no symptoms at all.

What causes papillary urothelial carcinoma?

Certain factors are known to increase the risk of developing papillary urothelial carcinoma:

• Tobacco smoke (the most significant known risk factor).

• Exposure to certain harmful chemicals, including opium, benzidine-based dyes, aromatic amines, arsenic, and aristolochic acid from herbal medicines containing Aristolochia plants.

• Chronic (long-term) bladder inflammation or irritation from infections like the parasite Schistosoma haematobium, and long-term use of urinary catheters.

• Medical treatments such as pelvic radiation therapy or chemotherapy drugs (e.g., chlornaphazine, cyclophosphamide).

Tumour grade: low grade versus high grade

Pathologists classify papillary urothelial carcinomas into low grade and high grade, based on how the tumour cells appear under the microscope.

• Low-grade tumours: Cells look similar to normal urothelial cells. These tumours generally grow slowly and have a lower risk of becoming invasive or spreading.

• High-grade tumours: Cells appear more abnormal—larger, darker, and less organized. These tumours are more aggressive, grow more quickly, and have a higher likelihood of invading deeper tissue layers and spreading beyond their original site.

Grade is important for predicting tumour behaviour, risk of recurrence, and guiding treatment decisions.

Non-invasive and invasive tumours

Non-invasive tumours

Non-invasive tumours remain confined to the urothelium, the inner lining of the urinary tract. These tumours do not invade deeper tissues and cannot spread to lymph nodes or distant sites. Non-invasive tumours can usually be cured with surgical removal alone.

Invasive tumours

Invasive tumours have spread beyond the urothelium into deeper layers, such as the lamina propria or muscularis propria (muscle). Invasive tumours can potentially spread to lymph nodes and distant organs, requiring more comprehensive treatment beyond surgery.

When invasive tumours are identified, pathologists carefully evaluate how deeply the tumour cells have invaded. The depth of invasion helps determine the cancer’s stage and influences further treatment strategies.

How is papillary urothelial carcinoma diagnosed?

Diagnosis typically involves multiple steps:

• Urine test (urine cytology): Examining urine samples under the microscope for cancer cells.

• Biopsy: Removing a small tissue sample, often through a procedure called cystoscopy, to confirm the diagnosis microscopically.

• Transurethral resection of bladder tumour (TURBT): A procedure used to remove the entire visible tumour from the bladder, providing both diagnosis and treatment.

• Partial or complete resection: For larger or invasive tumours, more extensive surgical removal may be necessary.

Why is sampling the muscularis propria important?

The muscularis propria is the thick muscle layer within the bladder wall. When removing tumours, doctors often include a sample of this muscle tissue to examine under the microscope. This step is critical because pathologists must confirm whether cancer cells have invaded the muscle. Identifying muscle invasion significantly affects treatment choices and prognosis. Your pathology report will typically indicate if the muscularis propria was included and examined.

Pathologic staging (pTNM system)

The pathologic stage describes how advanced the cancer is, based on the TNM system, created by the American Joint Committee on Cancer. This system considers:

• T (Tumour): The depth and extent of the tumour invasion.

• N (Nodes): The presence or absence of cancer cells in nearby lymph nodes.

• M (Metastasis): Whether cancer has spread to distant areas of the body.

Tumour stage (pT)

Tumour stage describes how deeply the cancer cells have invaded:

• Ta: Non-invasive tumours confined to the urothelium.

• T1: Tumour cells have invaded the lamina propria directly beneath the urothelium.

• T2: Tumour cells have invaded into the muscularis propria (bladder muscle).

• T3: Tumour cells have invaded into surrounding fatty tissue around the bladder (perivesical tissue).

• T4: Tumour has spread to nearby structures such as the prostate, uterus, or pelvic wall.

Nodal stage (pN)

This describes lymph node involvement:

• N0: No cancer cells found in any examined lymph nodes.

• N1: Cancer cells were found in one pelvic lymph node.

• N2: Cancer cells were found in multiple pelvic lymph nodes.

• N3: Cancer cells were found in lymph nodes located outside the pelvis (common iliac lymph nodes).

• NX: No lymph nodes were submitted or examined.

Higher stages typically indicate more advanced disease and may require additional or more aggressive treatment approaches.

Questions to ask your doctor

• Is my tumour invasive or non-invasive?

• What is the grade and stage of my tumour, and how does it affect my prognosis and treatment?

• What treatments will I require beyond surgery, if any?

• What is the likelihood my tumour will recur, and how often should I have follow-up examinations?

• Can my tumour become more aggressive over time?

• Are there lifestyle changes or precautions I can take to reduce the risk of recurrence?

• Should my family members be screened for this type of cancer?

• What symptoms or signs should prompt immediate medical attention?