High grade papillary urothelial carcinoma

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

High-grade papillary urothelial carcinoma is a type of cancer that starts from specialized cells lining the urinary tract. The urinary tract includes the kidneys, ureters, bladder, and urethra, with the bladder being the most common site for these tumours. This type of cancer is described as high grade because the tumour cells appear very abnormal when examined under the microscope. The term papillary refers to the tumour’s growth pattern, characterized by long, finger-like projections of tissue extending from the inner surface of the urinary tract.

High-grade papillary urothelial carcinoma can be either non-invasive or invasive, depending on whether cancer cells have spread into deeper tissue layers beneath the surface lining (the urothelium). This distinction is critical because non-invasive tumours typically have a better outcome and may be cured by surgery alone, while invasive tumours usually require additional treatments, such as chemotherapy or radiation therapy, following surgery.

Understanding the urinary tract

The urinary tract is responsible for removing waste and excess water from your body in the form of urine. It includes:

• Kidneys: Organs that filter your blood and create urine.

• Ureters: Thin tubes that transport urine from the kidneys to the bladder.

• Bladder: A hollow organ that temporarily stores urine.

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

The inner lining of the entire urinary tract is made of specialized cells called urothelial cells, forming a protective barrier known as the urothelium.

What are the symptoms of high-grade papillary urothelial carcinoma?

Common symptoms include:

• Blood in the urine (hematuria), which might make urine appear red or brownish.

• Pain or burning sensation during urination (dysuria).

• A frequent or urgent need to urinate.

• Lower abdominal discomfort.

Symptoms may vary among individuals, and some people may initially experience only mild signs.

What causes high-grade papillary urothelial carcinoma?

Certain substances and conditions increase the risk of developing high-grade papillary urothelial carcinoma:

• Tobacco smoke (smoking is a major risk factor).

• Exposure to chemicals such as opium, benzidine dyes, aromatic amines, arsenic, and aristolochic acid from certain herbal medicines.

• Chronic inflammation or irritation in the urinary tract, due to long-term urinary catheter use or repeated urinary infections, such as with the parasite Schistosoma haematobium.

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

Non-invasive vs. invasive tumours

Non-invasive tumours

In non-invasive tumours, cancer cells are confined strictly to the urothelium and have not grown into deeper tissue layers. These tumours usually have an excellent prognosis and can typically be cured with surgery alone.

Invasive tumours

In invasive tumours, cancer cells have grown beyond the urothelium, spreading into deeper layers of the urinary tract (like the lamina propria or muscularis propria). Invasive tumours have the potential to metastasize (spread) to lymph nodes and other organs, requiring additional treatments beyond surgery.

When your pathologist examines the biopsy, they assess how deeply the cancer has spread. This information helps determine the cancer’s stage (see section on “Pathologic stage”) and guides further treatment decisions.

How is this diagnosis made?

Diagnosis typically involves multiple steps:

• Urine test: Checking for cancer cells in the urine.

• Biopsy: During a cystoscopy (a procedure that uses a thin camera inserted into the bladder), the doctor removes a small tissue sample, which a pathologist then examines.

• Transurethral resection (TURBT): A procedure where the surgeon removes the entire tumour from the bladder. This method provides both diagnosis and treatment.

• For larger or deeply invasive tumours, surgery to remove part or all of the bladder (partial or total cystectomy) or affected kidney (nephrectomy) might be required.

Why is it important to sample the muscularis propria?

The muscularis propria is the muscular layer within the bladder wall. Sampling this muscle is crucial because pathologists must examine it microscopically to determine if cancer cells have invaded into this deeper tissue. This assessment helps confirm whether the tumour is invasive (potentially aggressive and needing additional treatment) or non-invasive.

Because the presence or absence of muscle invasion significantly affects treatment decisions, pathology reports always specify whether the muscularis propria was included and evaluated.

Pathologic stage (pTNM)

The pathologic stage describes the extent and spread of the cancer, using an internationally recognized system known as the TNM staging system. This system includes:

• T (Tumour): Size of the tumour and how deeply it has invaded.

• N (Nodes): Involvement of nearby lymph nodes.

• M (Metastasis): Whether the cancer has spread to distant organs.

Tumour stage (pT)

• Ta: Non-invasive tumours (limited to urothelium)

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

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

• T3: Tumour cells have grown through the bladder muscle and into surrounding fatty tissue (perivesical tissue).

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

Nodal stage (pN)

• N0: No cancer cells detected in examined lymph nodes.

• N1: Cancer cells found in one lymph node within the pelvis.

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

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

• NX: No lymph nodes were provided or examined.

Understanding the stage helps your healthcare provider determine the best treatment options and estimate prognosis.

Questions to ask your doctor

• Is my tumour invasive or non-invasive?

• What is my tumour stage, and what does it mean for my treatment?

• Will I require additional treatment beyond surgery?

• Do I need regular follow-up tests or procedures?

• Am I at risk of the tumour returning or spreading?

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

• Should my family members be screened for similar cancers?

• How often should I have check-ups and imaging studies to monitor my condition?