Bladder cancer is the fourth solid tumor for incidence in male population. Well recognized risk factors are cigarette smoking and exposure to aniline, a colorant. Some data suggest that in smokers the prognosis can improve after smoking cessation.
In 95% of cases the tumor arises from urothelial mucosa. A recent study from UK has shown that bladder cancer screening with urinalysis  (searching for small amount of red blood cells) could improve cancer survival from 80% to 100% in screened population. 
When microscopic blood is present in urine, the incidence of bladder cancer ranges form 0.5 to 10.5%, with a 3% median.
Macroscopic (visible) blood in urine is a symptom that should always be investigated until the source is found. 
If there is a rapid onset of urinary urgency (a sudden and unavoidable need to rush to urinate) in the last weeks or months, the chance of a cancer irritating the bladder should be considered. In these cases urinary cytology (microscopic examination of cells in the urine) can help diagnosis. 
The first approach in case of haematuria (visible blood in the urine) or suspicion of bladder cancer is an ultrasound scan of bladder and kidneys. In case of negative ultrasound or if there is a doubdt about the presence of bladder cancer, a cystoscopy is mandatory. It is performed with a small fibre optic through the urethra, up to the bladder. Usually it is well tolerated and can be performed as office procedure. To avoid the risk of urinary infection, a culture of the urine should be performed before the procedure.
Once the diagnosis of bladder cancer is established, a CT scan of abdomen and pelvis

can be helpful, especially at first diagnosis. In fact, a tumor of upper urinary tract can be associated to bladder cancer in 2-5% of cases. CT scan is also useful when hydronephrosis (dilatation of excretory ways of the kidney) is present or an invasive disease



The first approach to bladder cancer is Transurethral Resection of the Bladder (TURB). The procedure is usually performed in loco-regional (epidural) anaesthesia. With a fibre optic instrument introduced trough the urethra, with a small wire loop all the visible tumor is resected under vision and extracted



Often it is necessary to maintain an indwelling catheter for 1-5 days, according to the depth of resection, to the number and extension of lesions.
The procedure obtains an effective local staging of disease. Prognosis and treatment of bladder cancer differ considerably according to local stage, whether the tumor is superficial (not extending beyond mucosa or submucosa) or muscle-infiltrating (invading the muscular layer of bladder wall or beyond)



Staging of bladder cancer
TX:Primary tumor cannot be assessed
T0: No evidence of primary tumor

• Ta:Noninvasive papillary carcinoma
• Tis:Carcinoma in situ: "flat tumor"

T1: Tumor invades subepithelial connective tissue T2: Tumor invades muscle

• pT2a: Tumor invades superficial muscle (inner half)
• pT2b: Tumor invades deep muscle (outer half)

T3: Tumor invades perivesical tissue

• pT3a: Microscopically
• pT3b: Macroscopically (extravesical mass)

T4: Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, or abdominal wall

• T4a: Tumor invades the prostate, uterus, vagina
• T4b: Tumor invades the pelvic wall, abdominal wall

Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension
N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension
N3: Metastasis in a lymph node, more than 5 cm in greatest dimension

Distant metastasis (M)

MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis


In superficial bladder cancer (Ta, T1), which represents 75-80% of all bladder cancers at diagnosis, the prognosis is usually good, since seldom it tends to progress to muscle invasion (15%) or to distant metastasis. In case of a superficial bladder cancer T1 at resection, especially if high grade (G2-3), it is advisable to perform a second transurethral resection at 2-4 weeks. In fact, even after TURB of a skilled urologist, at the second resection residual tumor can be found up to 40% of cases. Moreover, even if there is no residual disease, the second resection seems to improve anyhow the prognosis. In superficial bladder cancer TURB must be considered a staging and therapeutic procedure. Local recurrence rate can be high in superficial bladder cancer, up to 50%-70%. This is due to the fact that bladder cancer is a multifocal disease, and the tumor may recur in a bladder site different from the site of resection. That´s why endovesical therapy with instillations is often used to reduce recurrence rate. A drug (usually a chemotherapeutic agent - Mytomicin, Epirubicin, ThioTepa, Gemcitabine - or an immune system stimulating bacterium - BCG- Bacillus Calmette Guerin) is introduces by a small catheter in the bladder once a week, for 6-8 weeks. Local chemotherapy has not the side effect of a systemic chemotherapy, since the drug is poorly absorbed through the bladder wall. Local chemotherapy is effective only at bladder level, with reduction of recurrence rate. However, intravesical chemotherapy doesn´t decrease the risk of progression to muscle-invasive disease. Clinical studies suggest that in most cases the first cycle of intravesical chemotherapy could be substituted by an equivalent immediate single intravesical instillation within 24 hours (even better within 2-3 hours) from TURB. All intravesical chemotherapeutic agents have nearly similar efficacy. However, promising results have been obtained with the recent introduction of Gemcitabine.
In aggressive superficial bladder cancer (high grade or with multiple recurrences), the best treatment option is local immunotherapy with BCG. It is a mild form of the Tubercolosis Bacterium, used for vaccination. Today it is the most effective intravesical agent known. It is especially valuable in high risk superficial cancer (G3, Carcinoma in Situ). Possible side effects are usually stronger with BCG therapy, and they may include fever, bladder irritative symptoms, haematuria, and very rarely urinary or extensive tuberculosis.
With any kind of intravesical treatment (BCG or chemotherapy) the literature has shown that the efficacy is improved by maintenance protocols (repeated cycles after the first ones) at scheduled intervals.
Though superficial, high grade superficial bladder cancer (G3T1) deserves special care. This tumor when treated with transurethral resection only, has a 50% progression risk. BCG therapy reduces the progression risk to 10-20%, according to different series.
After TURB f a superficial bladder cancer, patients should undergo regularly cystoscopy, according to the following schedule:  every 3 months in the first 2 years, every 6 months from the third to the fifth year, and once a year from then on. To date, no test has shown to be as effective as cystoscopy to detect cancer recurrence. Bladder cancer infiltrating the muscular wall of the bladder requires an open procedure, with removal of the bladder and prostate in the male and of uterus in the female patient (radical cystectomy).
All the regional (pelvic) lymph nodes must be dissected and removed. An extended lymph node dissection (minimum 20 nodes) seems to improve survival. The operation involves a urinary diversion, which means a way to expel the urine outside the body once the bladder has been removed. In majority of case it is possible to create a new bladder with bowel tissue. A 30-60 cm segment of bowel is isolated, opened, and reconfigured in spheroid shape. The ureters are sutured to the new bladder; an anastomosis is created between the bladder and the residual urethral stump.
After the procedure, the patient can void through the urethra, with normal self-perception.
However, nighttime´s urinary leakage can occur in 25-30% of cases. A stricture (narrowing) of the suture between the ureter and the neobladder occurs in 5-15% of patients, and may require another surgical procedure to avoid renal damage.
In women there is also the risk of a hyperdistension of the new bladder, with increase of storage capacity and the risk of chronic urinary retention.
In poor conditions patients, in patients with impaired renal function, or with disease extending to the bladder neck and/or the prostatic urethra, a neobladder is contraindicated. In these cases an incontinent urinary diversion, the ileal conduit, is performed. A small pre-terminal ileal loop is isolated, and the ureters are sutured to one end. The other end of the loop is sutured directly to the skin. With this procedure there is no continence, and the urine is constantly drained into a stoma bag applied on the skin through an adhesive plate. Though aesthetically less attractive, this diversion has a lower risk of complications.
To avoid the discomfort of an incontinent diversion, and when it is not possible to use the urethral sphincter for the continence, alternative procedures can be used to obtain continent reservoirs, like the ileocecal valve, intussusception of the ileal loop, or reconfiguration of the ileal loop (Montie procedure) or of the appendix. However, these diversions require self- catheterization, and the mechanisms of artificial continence are not always reliable and effective.
In the last 3-4 years, in laparoscopically trained center, laparoscopic radical cystectomy is expanding. As laparoscopic radical prostatectomy, the operation is performed through a small hole in the abdominal wall, where a fibre optic is inserted. The abdomen is distended with CO2. Through additional holes (ports) further instruments are introduced, and the procedure is guided by a microcamera. Once the bladder has been isolated, through a small 7-8 cm incision the bladder is removed and the urinary diversion is performed in open fashion.  Laparoscopic radical cystectomy can´t be considered a standard procedure yet, but it can be done in specialized centers.
Five years survival after radical cystectomy for muscle infiltrating bladder cancer is 50% in older series, but can reach 80% in recent reports.
In patients at high surgical risk, or refusing surgery, or in highly selected (single lesion, no residual disease at a second transurethral resection) and motivated patients, non invasive protocols with combined approach (radiotherapy and chemotherapy) may be considered. With this modality, in selected patients five-years survival is about 50%, and nearly 40-60% of these patients can preserve the bladder. However, it must be kept in mind that such protocols are not standard, and have to be considered experimental.
In cases wit metastatic disease (bone, liver, lung), chemotherapeutic schedules may provide a prolonged survival, but the prognosis is usually poor and just a few patients are still alive at 3 years.