How is bladder cancer diagnosed?

The diagnostic investigation begins with a thorough medical history and a physical examination. The doctor will ask the patient about past exposure to known causes of bladder cancer, such as cigarette smoke (either through personal smoking or through "second-hand" smoke) or chemicals. Also, because hematuria can come from anywhere in the urinary tract, the doctor typically order radiological imaging of the kidneys, ureter and bladder to check for problems in these organs. In this era, this is most often accomplished by a CT Urogram (CT scan focused on the urinary tract).
Diagnostic tools to check for bladder cancer include various types of urinalysis. In one type, the urine is examined under a microscope to look for cancer cells that may have been shed into the urine from the bladder lining (urinary cytology). Urine cytology is analogous to a Pap Smear, in this case looking for cancer cells that are sloughed off in the urine. Urine can also be tested for substances known to be closely associated with cancer cells (tumor markers).
The urologist's most important diagnostic tool is cystoscopy, which is a procedure that allows direct viewing of the inside of the bladder. This is most commonly performed as an office procedure under local anesthesia or light sedation. First, a topical anesthetic gel is applied, so the patient will feel little or no discomfort. The doctor then inserts a viewing instrument called a cystoscope through the urethra and into the bladder. Looking through the cystoscope, the doctor is able to examine the bladder's inner surfaces for signs of cancer. Modern cystoscopes are soft and flexible, and this procedure is generally well tolerated.
If tumors are present, the doctor notes their appearance, number, location and size. As removal (resection) of the tumors cannot usually be done under local anesthesia, the patient is then scheduled to return for a surgical procedure to remove the tumor under general anesthesia or spinal anesthesia. In a manner as before, the doctor inserts an instrument, called a resectoscope, into the bladder. This is a viewing instrument similar to the cystoscope, but contains a wire loop at the end for removing tissue. This procedure is done through the urethra and is called a transurethral resection of bladder tumors. The removed tissue is sent to a pathologist for examination. Pathologists are specialists who interpret changes in body tissues caused by disease.
In addition to removing visible tumors, the doctor may remove very small samples of tissue of any suspicious-looking areas of the bladder. A pathologist also examines this tissue.
If a biopsy is taken and bladder cancer is found, the pathologist who examines the tissue will grade the tumor according to how angry the cells appear. The most widely used grading systems classify tumors into two main grades: low and high. The cells of low-grade tumors have minimal abnormalities. In high-grade tumors, the cells have become disorganized and many abnormalities are apparent. The grade indicates the tumor's "aggression level"—how fast it is likely to grow and spread. High-grade tumors are the most aggressive and the most likely to progress into the muscle.
Staging of bladder cancers is based on how deeply a tumor has penetrated the bladder wall.  Table 1 lists stages of penetration using the TNM classification system.

Table 1 -- Staging of primary bladder cancer tumors (T)
Ta:	Noninvasive papillary tumor (confined to urothelium)
Tis:	CIS carcinoma (high grade "flat tumor" confined to urothelium)
T1:	Tumor invades lamina propria
T2:	Tumor invades bladder muscle
T2a:	Invades superficial bladder muscle
T2b:	Invades deep bladder muscle
T3:	Tumor invades perivesical fat
T3a:	Microscopic perivesical fat invasion
T3b:	Macroscopic perivesical fat invasion (and progressing beyond bladder)
T4:	Tumor invades prostate, uterus, vagina, pelvic wall or abdominal wall
T4a:	Invades adjacent organs (uterus, ovaries, prostate)
T4b:	Invades pelvic wall and/or abdominal wall

Stages Ta and Tis (in the urothelium) and stage T1 (in the lamina propria) are the non-muscle-invasive stages. Most Ta tumors are low grade, and most do not progress to invade the bladder muscle. Stage T1 tumors may be much more likely to become muscle invasive but many, especially if not initially deeply invasive of the connective tissue, can be managed successfully by resection and medications placed in the bladder (see below). Stage Ta tumors often recur after treatment but they tend to do so with the same stage and grade. Stage T1 tumors must be watched carefully for the possibility that they may recur at a higher and potentially lethal stage.
The Tis stage classification is reserved for a type of high-grade cancer called carcinoma in situ (CIS). CIS usually appears through the cystoscope as a flat, reddish, velvety patch on the bladder lining. It is difficult to remove and is best treated with immunotherapy or chemotherapy. If untreated, CIS will likely progress to muscle-invasive disease. CIS in the bladder is a serious finding – it is cancer not just a premalignant lesion.