Bladder Cancer

The bladder is located in the pelvis and stores urine.

Urothelial carcinoma is the most common type of bladder cancer. Less common types include squamous cell carcinoma, adenocarcinoma, and other rare tumors.

Urothelial bladder cancer is commonly divided into two major groups:

Non-muscle-invasive bladder cancer (NMIBC), including Ta, T1, and carcinoma in situ (CIS), has not invaded the muscular layer of the bladder. Most newly diagnosed bladder cancers fall into this group, although the risk of recurrence and progression varies substantially.

Muscle-invasive bladder cancer (MIBC) has grown into the bladder muscle and carries a greater risk of lymph node or distant spread.

One of the most important questions after diagnosis is therefore whether the tumor has invaded the muscle layer.

Bladder cancer is associated with long-term exposure to certain carcinogens and chronic injury to the urinary tract. Major risk factors include:

• Smoking, one of the most important established risk factors

• Occupational exposure to aromatic amines and other chemicals used in some dye, rubber, leather, paint, and printing industries

• Previous treatment with certain medications such as cyclophosphamide

• Previous pelvic radiation therapy

• Chronic bladder inflammation or long-term irritation

• Schistosomiasis in endemic areas, particularly in relation to squamous cell carcinoma of the bladder

• Older age

• Male sex

Smoking-related risk increases with the amount and duration of tobacco exposure.

Blood in the urine is the most common symptom of bladder cancer.

The urine may appear red, pink, or tea-colored, or blood may be detected only on a urine test. Hematuria can come and go, so the disappearance of visible blood does not necessarily mean that the underlying problem has resolved.

Other symptoms may include:Frequent urination、A sudden or urgent need to urinate、Pain or burning during urination、Difficulty urinating、Increased nighttime urination.

These symptoms can also occur with urinary tract infections, prostate conditions, or urinary stones and therefore do not diagnose bladder cancer on their own.

More advanced disease may cause pelvic or lower abdominal pain, back pain, hydronephrosis, fatigue, loss of appetite, unexplained weight loss, or swelling of the legs.

Visible, painless blood in the urine—particularly in an older adult or someone with risk factors such as smoking—should be medically evaluated.

Common tests include:

• Urine testing. Urinalysis can confirm the presence of blood. Urine cytology may also be used to look for abnormal urothelial cells, particularly when high-grade disease or carcinoma in situ is suspected.

  
  

• Cystoscopy. Cystoscopy is a central test for evaluating suspected bladder tumors. A thin instrument is passed through the urethra into the bladder so the doctor can directly examine suspicious areas.

  
  

• Transurethral resection of bladder tumor (TURBT). Suspicious tumors are generally removed or sampled through TURBT. The procedure provides tissue to determine the tumor type, grade, and whether it has invaded the bladder muscle. TURBT is also an important initial treatment for NMIBC.

  
  

• Imaging. CT urography, contrast-enhanced CT, MRI, or other imaging may be used to evaluate the urinary tract, surrounding tissues, lymph nodes, and distant organs.

Non-muscle-invasive bladder cancer (NMIBC)

Most patients with NMIBC are initially treated with TURBT.

Further treatment depends on the risk of recurrence and progression rather than being the same for every patient.

Patients with lower-risk disease may receive a single postoperative dose of intravesical chemotherapy followed by regular cystoscopic surveillance.

Patients with intermediate- or high-risk disease may require additional intravesical therapy. Bacillus Calmette-Guérin (BCG) is an important treatment for high-risk NMIBC, while intravesical chemotherapy is also used in selected settings.

For high-risk disease that persists or returns despite adequate BCG treatment, options may include radical cystectomy or selected bladder-preserving treatments.

Muscle-invasive bladder cancer (MIBC)

For nonmetastatic MIBC, radical cystectomy with pelvic lymph node dissection remains an important standard treatment.

For patients who are eligible for cisplatin, neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy has long been an important standard approach.

This area is evolving rapidly. In 2026, the U.S. FDA expanded approval of enfortumab vedotin plus pembrolizumab as perioperative treatment for patients with MIBC who are candidates for cystectomy, with treatment given before surgery and continued afterward. Availability and indications vary by country and region.

For selected patients who wish to preserve the bladder and meet appropriate criteria, a bladder-preserving trimodality approach may be considered. This generally combines maximal TURBT with concurrent chemotherapy and radiation therapy, followed by close surveillance.

Locally advanced or metastatic bladder cancer

Systemic treatment for advanced urothelial bladder cancer has changed substantially in recent years.

For patients who are candidates for combination systemic therapy, enfortumab vedotin plus pembrolizumab is now an important standard first-line option recommended by international guidelines. Enfortumab vedotin is an antibody-drug conjugate directed against Nectin-4.

When this combination is not appropriate or available, platinum-based chemotherapy remains important. Gemcitabine plus cisplatin may be used for cisplatin-eligible patients, while gemcitabine plus carboplatin may be used in selected patients who cannot receive cisplatin.

For patients whose disease does not progress after first-line platinum-based chemotherapy, maintenance immunotherapy with avelumab may be considered.

Molecular Testing and Targeted Therapy

Molecular testing has become increasingly important in locally advanced or metastatic urothelial cancer.

FGFR2 and FGFR3 alterations, particularly FGFR3 alterations, can provide an actionable treatment target. Erdafitinib may be considered for appropriately selected patients with susceptible FGFR alterations after prior therapy.

HER2 and other molecular features may also influence treatment options in selected patients as precision therapies and antibody-drug conjugates continue to develop.