Polip or Cancer ?
At the level of the bladder, we speak of polyp, tumor, or cancer of the bladder indifferently. If the term “polyp” usually describes the benign superficial tumors, there is no practical distinction between polyp and cancer.
Bladder tumors are like a grey scale, with benign polyps being white, and the cancers being black. What really counts is the stage of the lesion, because this stage determines the prognostic and the treatment.
Kidneys, bladder: better prevent than cure. The risk of kidney and bladder cancers can be increased by the way of life and personal environment. Be careful with smokes, vapours and colourings. Tobacco is the main risk factor: it triples the risk of developing a cancer of the bladder (10700 new cases in 2000) especially in patients that started smocking early and in a high amount. “Stopping cigarette smoking decreases the risk, but also tumor progression” says Dr Jean Louis DAVIN, chairperson of the French urology association of cancer committee and urologist in Avignon.
Professional risks are also to be considered: persons exposed to the solvent: trichloroethylene, used in textile industry, or petrochemical, metallurgical and certain paints, are especially affected by kidney cancers (8300 new cases per year in France, increasing by 2% per year). Other products, especially colourings, are pointed at in the appearance of certain bladder cancers. The disease can manifest itself many years after exposure, doctors advice everyone, including retired people, to consult if in doubt.
What are the different types of bladder tumors?
The majority (90%) of bladder tumors keeps some characteristics of normal bladder mucosa and are said to be urothelial (from urothelium: internal lining of the bladder). Rarely, bladder tumors are different, and are said to be “non-urothelial” (in particular when the tumor is linked to the chronic irritation of the bladder wall by calculus, probe, bilharziosis…). Certain tumors are exceptional: melanoma, pheochromocytoma, lymphoma, choriocarcinoma).
How to determine the severity and prognosis of tumor?
The prognosis depends on the grade and the stage of the tumor. The grade depends on the prominence of cellular abnormalities within the tumor, the grade increases with more cellular abnormalities. The stage is determined by the depth of invasion of the tumor through the bladder wall (depth reached by the tumor “roots”) , the eventual extension of the tumor beyond the bladder (invasion of the surrounding fat tissue, neighbouring organs such as the prostate) and the occurrence of lymph nodes invasion or other distant organs (metastasis).
The stage is defined by the TMN classification, the most recent one. The different stages: in practice regarding the treatment and the prognosis, there is a distinction between superficial and infiltrative tumors.
The majority of bladder tumors are superficial, meaning the roots only invade the bladder wall superficially. There are called superficial polyps, papilloma, superficial tumors…. The polyp usually resembles a raspberry or an anemone with the fringes implanted in the bladder wall (it’s the base of the polyp) and also float in urine, like algae. We can have either single or multiple tumor, papilloma (fringes) or sessile (large base). Sometimes polyps occupy a large part of the vesical lining, leaving little disease free bladder mucosa: bladder papillomatosis.
Carcinoma in situ:
It is a flat tumor, non papillomatous, located in the mucosa depth. It can be single (10%) but most of the time associated with one or more polyps.
Those tumors usually have less fringes, they are said to be infiltrative because their roots go deep in the bladder wall, reaching the muscular layer (that contains the muscular fibers of the bladder)
What is the frequency of bladder tumor?
The average age of patients at diagnosis is 65 years old. Bladder cancer is 3 times more frequent in men than in women. Half of the cases can be attributed to tobacco, the major risk factor; which mainly explains the highest frequency in men. There are other risk factors: toxic products exposure in industry workers (colorings, chemicals), chronic infection especially chronic parasitic infection (bilharziosis) in West Africa and Egypt.
At the time of diagnosis, 75-85% of patients have a superficial tumor invading the mucosa (Ta, 70%), the chorion (T1, 30%) or intra epithelial (carcinoma in situ). Basically, 50-70% of superficial tumors recur, most of the time in the next 12 month and with the same stage and grade.
In case of superficial region, the natural history of the patient is unpredictable: recurrence more or less early, with more or less localizations, with same grade and same stage, or with a progression to an invasive tumor (5-30%). 80% of infiltrative tumors start as infiltrative without previous bladder lesion.
What are the signs for bladder cancer?
The most frequent, common and specific sign for bladder cancer is blood in urine. The urine can be bright red in case of abundant bleeding, or recent bleeding, but it can also be dark brown (wine color). In case of bladder tumor the bleeding usually occurs at the end of the flow (terminal hematuria). Generally, the bleeding is isolated, not associated with fever, pain or other symptoms. The bleeding is usually intermittent, and the fact of having bleeding and then clear urine should not reassure.
In case of abundant bleeding, clots can form and obstruct or stop the flow. The amount or duration of bleeding doe not relate to the cause of the bleeding: benign lesion can lead to heavy bleeding whereas infiltrative tumor may not bleed at all.
Sometimes there is no visible blood in urine, but blood is detected during a routine exam. This type of bleeding (microscopic) should be investigated like a heavy bleeding.
It is important to know that many other causes can lead to bleeding: infection (cystitis in women, or prostatic infection in men), renal stones, or recent prostatic biopsies.
Polyps can lead to the urge of voiding many times per day (frequency), a strong urge to urinate (urgency) or recurrent urinary infection ( due to the polyp)
What are the tests to be done in case of suspicion ?
It is the first test ordered by the doctor. It can confirm the presence of blood in urine and evidence of urinary infection that could explain this blood. In the particular case where blood has been detected by the urinary dipstick (during a regular check up for instance) it is essential to double check the presence of blood in a specialized laboratory. There are a lot of false positive tests with dipsticks.
Bladder fibroscopy (Cystoscopy):
This tests allows examinantion of the inner bladder via an optical technique. Flexible instruments with painless insertion in the urethra, has replaced the regular cystoscopy with hard instruments. This test can be done in the office after anesthesia of the urethra by an anesthetizing gel. Fibroscopy allows detection of a polyp, to determine its aspects, and its localization.
In case of tumor detection, its removal can be planned via the natural tract (endoscope resection)
It is the exam of desquamated cells that are naturally eliminated in the patient’s urine. Their exam allows detection of anomalies, which is very useful for the diagnosis, the follow up and in particular detection of recurrence after treatment.
Radiography if the urinary tract that is done by the intra venous infusion if an iodine product. This test is not very sensitive for tumor diagnosis (fibroscopy is more sensitive) but it allows for the imaging of kidney and urethers for an associated tumor.
Bladder ultrasound :
It allows detection of a papillary tumor according to the size of the lesion, the filling of the bladder, the skills of the operator. Usually the tumor is an incidental finding found when doing an ultrasound for another reason (gynecology evaluation in women, evaluation of prostate adenoma in men).
What is the treatment of bladder cancer ?
Stage dependent treatment. The first step in treatment is the ablation of the polyp through the natural ways (endoscopy) which removes any visible lesion, and allows for microscopic analysis in order to determine the stage and grade of the tumor. The treatment then depends on the stage, grade and general state of the patient. In superficial tumors, disease control and long term survival are obtained by simple ablation of the tumor with or without additional treatment by intravesicle infusion (BCG or Mitomycine).
For the majority of infiltrative tumors (deep), the ablation of the tumor is the most effective treatment. With those that invade locally (lymph nodes) or distally (metastasis) the usual treatment needs chemotherapy with or without concomitant radiotherapy.
Endoscopic resection of bladder tumor
In all cases of bladder polyp, the first step is to remove it. It is done under general anesthesia, or by anesthetizing only the lower part of the body (spinal anesthesia). We use an instrument (resector) introduces in the urethra, which allows to scrape the polyp and to coagulate the implantation zone.
At the end of the operation, we introduce a urinary catheter that allows for lavage of the bladder. It is removed 24 to 48 hours post-operation. The polyp(s) are examined microscopically, which allows for detection of their superficial or deep characteristics.
It consists of infusing a liquid in the bladder which will act on its wall. Their goal is to decrease the risk of recurrence of superficial tumors. This procedure is used in case of recurrence of superficial tumor one year after resection of the primary one. Also used in case of multiple bladder tumors, and if the tumor is mildly infiltrative (pT1). BCG and Mitomycine are the 2 most common products used. The infusion is done after removal of all the bladder polyps. BCG: The bacillus Calmette-Guérin s usually used for Tuberculosis vaccination.
It’s mechanism of action is unknown, but it seems that it activates the immunity of the bladder wall leading to it rejecting tumor cells. It efficacy in prevent or delay the recurrence of bladder tumors has been discovered in 1975. The prophylactic activity of BCG is about 60% in recurring superficial tumor, and 70% in carcinoma in situ. The treatment consists of one infusion of BCG every week for 6 weeks, then 3 infusions 3 month later. The treatment protocols can vary.
In case of multiple recurrences, some advice a maintenance treatment once a month, but the benefits are not proven. Different strains of BCG have been used, but the one now used in France is the lyophilised one (Immucyst®). Mitomycine C (Amétycine®): this antibiotic is also used against tumors, with weekly infusion for 8 weeks. Thiotépa®: this product was used in the 80’s.
How does the infusion happen?
To infuse the products a small catheter in inserted in the urethra and the product is injected in the bladder. The catheter is then removed and the patient keeps the product in the bladder. A contraindication for this procedure is if there is blood in the urine. (Risk of infection by BCG). The infusions are done on an outpatient basis and don’t require anaesthesia. To improve the efficacy of the treatment, it is advised to stop drinking the night before. In addition it is asked of the patient not to drink and not to urinate for 2 hours after the infusion (to increase the duration of contact between the product and the wall).
The treatment is usually well tolerated except for irritative symptoms 24 to 48h after infusion. It is common with BCG to have urinary troubles (frequency and urgency) or even mild fever at night or on the next day. These troubles are usually transient. If they persist, we can separate the infusions by more time, or advise an analgesic/anti inflammatory treatment. It is essential to contact the urologist in case of high grade or persistent fever.
The infusion is repeated once a week for 6 weeks (BCG) or 8 (Mitomycin C). A check up of the bladder by fibroscopy is usually scheduled for 4-6 weeks after the last infusion.
Bladder ablative surgery (Cystectomy)
Cystectomy and its derivatives are done by our team, through laparoscopy.
Bilateral ilio-obturator resection
It’s the ablation of lymph nodes located on both sides of the bladder. It’s done right before the bladder ablation, and analysis is done immediately (frozen section). In case the lymph nodes are affected, we do not remove the bladder, but prefer chemotherapy.
Complete ablation of the bladder (radical cystoprostatectomy)
It consists in removal of the bladder, the fat tissue surrounding it, the prostate, the seminal vesicles as well as the urethra.
Ablation of the bladder in women
It is done by both an abdominal and a vaginal approach. It consists in removal of the bladder and its surrounding fat tissue, the urethra, the uterus as well as a part of the anterior vaginal wall.
Partial ablation of the bladder (partial cystectomy)
This option is attractive when the invasioin of the tumor is limited to the superior bladder wall. But it is usually not advised due to the risk of recurrence cause by the opening of the bladder. This procedure is reserved for single tumors at the top of the bladder, well circumscribed, with normal marginal biopsies, and no carcinoma in situ, especially in elderly patients. This corresponds to about 5% of invasive bladder tumors. Radiotherapy can be added to decrease the recurrence rate.
Re establishment of the urinary continuity
If the bladder is removed, a new circuit has to be created for the urine to flow from the kidney through the urethers. Urine can be diverted through the skin (they are accumulated in a pocket stuck on the skin), in the colon (it is evacuated through the rectum with the stools), or a new bladder made by intestinal wall can be inserted so that the patient continues to urinate through the natural circuit.
It is the direct anastomosis of the urethers to the skin. The patient has 2 pockets (one on each side) This technique is not used anymore.
Cutaneous tran-ileal diversion (Bricker):
It is the diversion of the urine to the skin through a piece of intestine between the urethers and the skin opening. The advantage of this technique is that the patient only carries one pocket that drains urine from both urethers. This technique is widely used because of reliability and easiness for the patient.
Replacement of the bladder after cystectomy (bladder removal)
It’s the diversion of the urine trough the colon. We anastomose the urethers above the rectum. But before that, the anal sphincter tone (that closes the rectum) is good enough to retain urine.
Bladder replacement allows the patient to obtain a semi normal function; since the urine is still eliminated by the natural way. This technique is feasible in men, but more difficult in women because of the short length of the urethra. In certain selected cases where it is possible to keep the urethra, bladder replacement can be done in women.
In general, within weeks (8-10) patients obtain a normal continence during the day, and semi normal at night, with 2-3 times to the bathroom. In the bowels, the intestinal mucosa still produces mucus, which is eliminated in urine as whitish threads, not to be mistaken for an infection. Drinking a large amount of fluids is necessary to prevent urethra obstruction by a mucus plug. The follow up after cystectomy is simple: Ultrasound and/or intra venous urography are done every 2 years, and kidney function is also regularly assessed.
A piece of intestine is used to create a pocket between the urethers and the urethra.
Diversion of urine to the skin according to Becker’s technique Intestinal piece is positioned between the urethers and the skin.
Alone, it is used in a palliative goal, in case the surgery is contra indicated (patient old, fragile…)
Chemotherapy is used in case the tumor has overgrown the bladder, in particular when the lymph nodes are affected, having the bladder removed or not. The best responses rates and survival rates were obtained by the M-VAC protocol, that associates methotrexate, vinblastin, adriamycin and cisplatinum. A cycle is done every 28 days. Other protocols are also used:
This technique associates moderate dose radiotherapy with a “mild” chemotherapy. Synergy of both treatments can prevent bladder removal in certain minimally infiltrative tumor. Biopsies of the bladder are usually obtained at half the dose, in order to decide on the rest of the protocol: If normal biopsies, bladder salvage and continuation of the protocol. If residual tumor: removal of the bladder.
- Protocol CMV: (cisplatinum, methotrexate, vinblastin) especially when adriamycin is contra indicated due to cardiac problems.
- Protocl CISCA (cyclophosphamide, doxorubicine, cisplatinum)
In case of superficial tumor, the survival rate at 5 years after treatment (endoscopic resection/or intra vesicle instillations) is 80 to 90%. The response rate after BCG is 70-100% in case of carcinoma in situ and 80-90% in case of superficial tumor. Patients with carcinoma in situ that respond to BCG treatment have a progression risk at 5 years of about 20%, whereas patients with incomplete response have a progression risk of 95%.
The survival rate at 5 years post cystectomy is of 40-70% incase of T2 infiltrative tumor, and 15-40% for T3 infiltrative tumor.
Kidney and uretheral epithelial tumors
These are tumors of the internal lining of the kidneys (wall in direct contact with urine) and the urethers. The lining has the same characteristics as the bladder, therefore the tumors are urothelial in type. Compared to bladder cancer, these cancers are rare, and consist of 4% of all the urothelial tumors. Among those patients, 30% have an associated bladder tumor.
The most frequent symptom is blood in urine (hematuria) and pain (due to the obstruction by tumor or stone) The diagnosis is made by radiography after infusion of contract (intra venous urography), unprepared scan (in case diagnosis is doubted for stone), flexible uteroscopy, urether retrograde opacification.
Treatment of upper genitor urinary tumors
The usual treatment is nephro-ureterectomy, which consists of removal of the kidney and the urether all the way to the bladder. In case of isolated tumor of the terminal urether, next to the bladder, we can do a segmented removal of the urether with re implantation of the urether to the bladder. In case of metastatic tumor, we use chemotherapy with the MVAC protocol, similar to the one used in bladder tumor.