How Does the Normal Bladder Work?

The bladder is a muscular, expandable sac in the pelvis, normally about 3 inches across. It collects urine from two ureter tubes, one from each kidney. These ureters enter the bladder at the top, and fill it.To empty, the bladder drains the collected urine down through the single urethra tube, which comes off of the bladder at it's bottom. In males the first part of this urethra is surrounded by the prostate gland, and the remainder surrounded by the penis. In females, the urethra is shorter an exits out to a hole ("meatus") between the upper vaginal folds. In both males and females, the front of the bladder rests against the muscular pelvic wall; the rear of the bladder rests against the rectum in males,while in females the uterus lies between the bladder and rectum. It's upper surface is covered with a protective membrane ("peritoneum") . A muscle,the"urethral sphincter", surrounds the urethra to control urine output.

The empty bladder it triangular, it assume an oval ("ovoid") shape and pushes up into the lower abdomen as it fills up. The inside of the bladder is lined with a layer of cells, called "transitional epithelial" cells, which slide over each other to expandthe bladder lining as it fills. These cells are about 7 cell layers thick in empty bladder, but only 2 layers thick in the full bladder. The bladder receives blood from major branches ("internal iliac") off of the body's main artery ("aorta"). It drains blood via large pelvic veins, ultimately back to the main main ("vena cava"). Another way that tissue fluids can drain from the bladder wall is via the "lymph system", which purifies the blood. Lymph channels collect these fluids, and connect to "lymph nodes", filled with white blood cells,which filter them. After being purified, these fluids are returned to the bloodstream. Both the blood vessels and lymph channels can act as conduits for spread of infections or cancers. The bladder has a supply of nerves to tell it when to contract, and squeeze out urine. If these nerves are malfunction from disease or medications, the bladder will not fully empty, that is have "residual" urine. A bladder that has completely lost it's nerve supply is called "atonic" and these patients need a tube place("catheter") to drain urine.The most common problem with the bladder is a urinary tract infection ("UTI") . Any process that infects or inflames the bladder is called "cystitis" in medical parlance.

What is Bladder Cancer?

The bladder is composed of various "cells", which are intricately combined together into "tissues" which form the "organ" . These cells divide to produce new ones, and grow very rapidly during womb life, early childhood and puberty. In adulthood, new cells are produced only to replace those that die of old age, injury or disease. Normally, division of cells is under very tight control. This control is exerted by the "genes" inside each cell, which are housed in long clumps forming "chromosomes", which are visible under a light microscope. The genes themselves are made up of DNA, the master genetic code material. If the genes are damaged, say by chemicals or radiation, the control over cell division may be lost in one particular cell. Ultimately, cancer is considered a disease of the DNA. Bladder cancer starts in a single cell . That cell starts dividing haphazardly, making millions and billions of copies of itself. It takes up the nourishment needed by other cells, depriving them so the cancer can continue to grow. Quickly growing cells can clump up to form a "tumor" . A tumor simply means a swelling, it can be caused by inflammation or infection. A "benign" tumor only grows in it's local area (although it may get quite large)-- it cannot spread and is not cancer. By contrast, a tumor which can spread to other body areas is called "malignant" and this is cancer . The process of cancer spread to other areas is called "metastasis", so only malignant tumors ( i.e. cancer) can metastasize. Theoretically, cancer can spread to any area of the body, and it often grows better in it's area of spread than in it's area of origin("primary site") . It is this capacity for spread that makes cancer so dangerous. If not treated successfully, bladder cancer ultimately kills by urinary blockage, debility, anemia, infection, and damage to distant organs like the liver and brain.

How Common is Bladder Cancer?

Each year in the U.S.A. there are 52,000 new cases of bladder cancer, and it causes 12,000 deaths . It thus accounts for about 6% of all new cancers. It is three times more common in men than women, and is the 4th most common cancer in males. The average patient is 65 years old; only 1% of patients are less than age 40.It is somewhat more common in White individuals than Blacks.

What are the Types of Bladder Cancer?

The most common type starts on the inner lining of the bladder, and arises from the "transitional cells" . Therefore, it is called"Transitional Cell Bladder Cancer" and makes up 92% of total cases. It can either be"Superficial" , meaning that is confined to the inner lining (and spreads along it), or"Invasive", meaning that it penetrates into the muscular wall of the bladder. The treatment for "Superficial" cancers is different than for the "Invasive" type. Furthermore,cancers have varying shapes or "morphologies" when examined without magnification. The Papillary type (70%) looks like raised bumps, while the Solid Infiltrating type (25%) invades deeply earlier. Another less common type of bladder cancer is called "Squamous Cell Carcinoma" ; it arises from cells similar to those of the mouth and anus. The squamous cell type represents 6% of bladder cancers. The remaining 2% of bladder cancer is comprised of rare types, like "sarcomas" which arise from muscle ("rhabdomyosarcoma") or fat ("liposarcoma") , and"lymphomas", which develop from the bodies immune system cells. The treatments discussed in this transcript are for the Transitional Cell and Squamous Cell types . Treatment forrare types is discussed in special transcripts on "Fat and Muscle Cancers", and "non-Hodgkin's Lymphomas".
What Causes, or Increases the Risk of Bladder Cancer?

Like any cancer, the precise reason why one person gets bladder cancer and another does not remainsunknown . However, several things have been noted, when studying groups of patients, that seem to increase the risk.These"risk factors" are:

For "Transitional Cell Bladder Cancer":

1) Cigarette Smoking increases the risk 3 times over non-smokers. If one quits smoking, the risk decreases after 5 years and nears normal at 15 years.
2) Carcinogen Exposure means being exposed to cancer-inducing chemicals. Examples include coal tar and synthetic dyes made from aniline. It often takes as long as 20 years after exposure (called a "latent period") to get the cancer.
3) Family History of bladder cancer in close relatives doubles the risk.
4) Place of Residence -- Bladder cancer is more common in Industrial than Undeveloped areas, and more common in Urban than Rural areas.
5) Medications like Phenacetin (not available in U.S.) and Chemotherapy agents like Cyclophosphamide and Chlornaphazin.
6) Being White, Older, and Male is higher risk than Black, Young and Female.
7) Having Bladder Polyps, especially"dysplastic" types. There are various types of polyps, including simple outpouchings of flesh which are totally benign ("hamartomatous polpys"), glandlike ("adenomatous")polyps and those with pre-malignant changes ("villous" or "dysplastic") polyps.

For "Squamous Cell Carcinoma":

1) Chronic Irritation of the bladder, such as from repeated Urinary Tract Infections or long-term "indwelling" catheter use to drain an atonic bladder.
2) Infection with a Parasite called "Schistosoma" (rare in the U.S.)

Alcoholic Beverages, Dietary Sweeteners, and Caffeine are NOT proven to increase risk for any type of bladder cancer in humans.

Can Bladder Cancer be Prevented?

Milk, Vitamin A, andVitamin D are thought to reduce the risk of bladder cancer by one-half. Early detection of new bladder cancer, and prompt treatment, will reduce death from this disease.

What are the Symptoms of Bladder Cancer?

Like any cancer, very early bladder cancer will have no symptoms, since the disease has not grown large enough to interfere with normal functioning. When symptoms do arise, they are most commonly:

Blood in the Urine ("Hematuria") is the most common sign of bladder cancer, found in 80% of cases. The bleeding may be either "gross" (easily visible) or "microscopic" (detected only on urinalysis at the doctor's office). However, blood in the urine is not necessarily from cancer; kidney stones, infection, medcations and trauma may all cause hematuria . In about one-third of bladder cancer patients, symptoms of Urinary Tract Infection ("UTI") including irritation and frequency, are noted which prompts the urinalysis. It is common for polyps of the bladder, especially dysplastic ones, to send scant bleeding into the urine, and to become infected if the patient is prone to UTI's. Infection of anatomically abnormal structures, like polyps, is often harder to treat since the distorted anatomy acts as a sanctuary to protect bacteria from antibiotics. Some of these polyps may be malignant.In cancer patients, anewly very irritable bladder often means invasion of the bladder's muscle wall by tumor. It is common to have a UTI along with a superficial cancer causing irritation.

Obstruction of Urine inflow by ureter blockage, or urine outflow by urethra blockage, are seen with larger cancers. If urination is blocked, the poisons in the urine (e.g. urea) will build up in the bloodstream, causing"uremia". When pressure backs up the kidneys, they get damaged ("hydronephrosis"). Patients with uremia itch ("pruritis"), get very tired, and their ability to think clearly decreases ("uremic encephalopathy"). It will become fatal unless the obstruction is cleared, or the patient's blood is purified with "dialysis".

Pain is felt in the flanks as blockage enlarges the kidneys, and pelvic pain as the cancer invades into nerves. This pain tends to worsen over time.

Signs of Distant Spread include liver pain from spread to this organ and stretching of it's capsule, bone pain from spread there, and neurological symptoms (paralysis, numbness, stumbling,memory loss, seizures) if it metastasizes to the brain. Bladder cancer can spread to any body area.

Nearly 20% of patients do not have ANY symptoms when their disease is found!

How does Bladder Cancer Spread?

As mentioned, bladder cancer starts in a single abnormal cell. This cell divides to make millions and billions of copies of itself, forming a tumor. A superficial malignant tumor tends to grow along the inner lining of the bladder, but an invasive ("lymphadenopathy") . This swelling may be noted in the groin, or cause back pain by involving lymph nodes there ("paraaortic nodes").Cancer cells shed into the tiny draining veins of the bladder, where they can travel to the liver, bone, lung and brain. The original tumor (called the "primary site" ) continues to grow, it can penetrate the outer wall of the bladder to invade into the rectum, kidneys, uterus, vagina or prostate. The cancer can metastasize to the bowel by spreading via the intestinal surfaces ("peritoneal spread"). As it invades nerve bundles, it causes pain. While the cancer may spread to any organ, over 80% of patients succumbing to bladder cancer have disease remaining in the pelvis area ("local disease") at their time of demise.

How is Bladder Cancer Detected and Evaluated?

Like any cancer, the only absolute way that bladder cancer can be diagnosed with certainty is by getting a sample of it, called a"BIOPSY", for examination. The cancer can be sampled by:
1) Looking for malignant cells shed into the urine ("cytology") .
2) Sampling a swollen lymph node.
3) Placing a scope up to the bladder ("cystoscope") and cutting off a piece of tumor from the bladder wall, or cutting off suspicious looking polyps to send for analysis.
4) At open pelvis surgery.The biopsy material is studied under the microscope by a"Pathologist", a physician who specializes in diagnosing diseases through tissue samples.

When a patient comes to the doctor with suspicion of bladder cancer, the following is done:

Complete History and Physical Examination with special attention to the groin, pelvis, and abdominal areas. The patient is carefully questioned about changes in urinary habit, new pain, bleeding and bowel movements.Signs of anemia, uremia, infections ,and recent weight loss are noted. The abdomen is checked for liver and spleen swelling (hepato-splenomegaly");the groin,armpits ("axilla") and area above the clavicles ("supraclavicular") for lymph node enlargement. Neurologic exam is done; the male prostate is checked, as is the vagina, uterus cervix, ovaries, vulva and breasts in females.

Cystoscopic Examination means placing a visualization tube with a special biopsy cutting scissors into urethral opening (at the tip of the penis or vagina), through the urethra, and into the bladder. This procedure is performed by a "Urologist", a surgeon specializing in care of the genito-urinary tract. Cystoscopy is performed. Spinal anesthesia may be used to completely numb the lower body; a mild mixture of demerol and valium may be used for a light ("twilight") anesthesia. The general condition of the bladder and is noted, with attention to the area of entry of the ureters, the urethra, the appearance of the lining, and tumors.A diagram is marked into the medical record to show the location of any abnormalities. A biopsy is taken of any suspicious areas, and sometimes "blind biopsies" are taken of areas most likely to develop cancer (back wall or neck). To get a better look at the ureters, "Retrograde Ureteropyelography", multifocal disease (separate cancers in more than one area of the bladder) or even a "second primary" (another simultaneous cancer elsewhere) when they first come to medical attention. Cystoscopyis a very safe procedure, it can easily take small biopsies, and is the clearest way (besides open surgery) to actually look at tissues of the genito-urinary tract.

Blood and Urine Tests are standard pre-operative ones to assess general health; there are no special blood tests("tumor markers") yet to detect spread of transitional bladder cancer as for some other cancers. Routine tests will include Complete Blood Count("CBC") to look for anemia and infection. If bladder tumor or polyps have been chronically bleeding, this can result in a "microcytic anemia" (with smaller than normal red blood cells); these smaller cells appear "washed out" as they are low in Iron, necessary for hemaglobin. Blood Chemistry Panel ("SMA") measures sodium, potassium, blood sugar, cholesterol and liver and kidney function. If a major surgery is contemplated, blood tests for clotting ability (PT, PTT and bleeding time ) are standard. A Urinalysis(UA) to check for protein, blood or infection completes the lab tests. If the specimen is carefully collected ("clean catch") it can be sent for"culture and sensitivity".

Imaging Tests are done in the radiology department and standardly include a Chest X-ray to look for signs of infection or lung tumors. "Free air"in the chest is seen if the tumor has penetrated the bladder. An Intra-Venous Pyelogram ("IVP") if often used to see if there is any obstruction blocking the kidneys, ureters, or bladder. It is usually the first test gotten when a patient presents with hematuria, but is not the most accurate. It is good for identifying radio-opaque kidney stones, a common cause of blood in the urine and pelvic pain. IVP is generally a safe test; the main danger is an allergic reaction to the injected dye, or the kidneys shutting down from this dye.

When cancer invades the bladder wall, tests are done for local spread. CT scan in "thin slices" of the tumor area helps define the extent of the tumor, and is excellent for looking for spread to lymph nodes around the bladder which cannot be detected on standard physical exam. Another excellent test to study the soft tissues in the pelvis is the expensive Magnetic Resonance Imaging(MRI) scan. MRI, which uses magnetism instead of radiation, allows the area to be viewed in three dimensions. It is great for looking at the tumor as well as checking local muscle, fat and nerves for signs of invasion by cancer. Contrast material can be injected into the blood stream prior to either CT scan or MRI, the contrast runs through and highlights blood vessels. If getting a CT with contrast, ask for"omnipaque" contrast; other types are less expensive but more likely to cause an allergic reaction. For MRI scans, a differ- ent type of contrast, called"gadolinium" is used. Other more exotic tests are only obtained in the presence of suspicious symptoms. For instance, a bone scan is gotten if there is new bone pain, a CT of the chest is ordered when the plain Chest -ray appears to show tumor in the lung, and a CT of the Brain is gotten if new neurological symptoms occur. Certainly, other areas of the gastrointestinal tract (such as the colon and rectum) may need to be examined. If major surgery is contemplated,Lung Function Tests("FEV") are done in the pulmonology dept.to assess lung capacity. AnEKG is gotten to rule-out recent heart attack, and if heart abnormalities are suspected a stress-thalliumand/or echocardiogram look at the heart. Tests can be ordered to look at any area of the body-- but only if necessary.

Biopsy (sampling)is crucial, since only by examining an actual sample of the tumor under the microscope can a diagnosis of cancer be made, and then the particular type known with certainty. For a very small tumor, the whole of it may be removed, along with a "safety margin" of surrounding normal tissue, and sent for evaluation ("Excisional Biopsy") . For a larger tumor, a cut is made into it so some tissue can be removed for examination("Incisional Biopsy") . It usually takes several days (of anxious waiting) for the pathology report to come back.

A pathologist is a physician who specializes in diagnosing disease from tissue samples. The pathologist will confirm or deny cancer in the "biopsy specimen", and name the particular type and "grade" if cancer is found."Grades" are given as I, II or III and indicate the probable aggressiveness of the cancer. "Grade III" is "high grade", shows rapid cell divisions, and doesn't look much like normal bladder tissue. It is likely to be aggressive. The most aggressive type tend to be "undifferentiated" carcinomas who's cell of origin is unclear. On the other hand, "Grade I " will look a lot like the normal tissue it arose from, have relatively few cell divisions, and tend to be more "indolent" (slower to grow and spread). "Grade II" is intermediate in behavior. The pathologist may need special stains and even an electron microscope to precisely characterize the cancer; there may be more than one type of cancer or grade within a given tumor ("mixed tumor").

The only sure way of accurately guaging the extent of cancer is by surgical exploration of the pelvis by exploratory laparotomy.

How is the Extent of Bladder Cancer Guaged?

Like all cancers, the extent of bladder cancer is given by the "stage" . A staging system in wide use is from the American Joint Cancer Committee ("AJCC") . This staging is numbered "0" through "IV" . The American Urological System is comparable, and labels the stages as "0" and"A" through "D" . Both systems are based upon a surgical knowledge of the depth of invasion into the bladder wall. Patients who are not going to be receiving surgery can be"clinically staged", basically meaning best-guess from the physical exam, cystoscopy and biopsy results, and imaging tests.

Stage 0 or "Carcinoma-in-Situ" (CIS) means the cancer doesn't invade into the bladder; it often does not progress any further at all. Often CIS is found in the head of dysplastic bladder polyps.
Stage I or "A" means the cancer is superficial, limited to the bladder's lining . This includes cancer in polyps which migrates down stalks.
Stage II or "B" means the cancer has spread into the bladder's muscle wall .
Stage III or "C" means the cancer has spread through the muscle wall into the fat that surround the bladder, called the "perivesical fat".
Stage IV or "D" means the cancer has spread to either lymph nodes around the bladder, or to other organs such as lung, bone, or brain.

How Curable is Bladder Cancer?

This depends upon many factors, including how aggressive the cancer is ( "grade") and how extensive it is("stage") . The cure rate also depends upon the general medical condition of the patient, their ability to tolerate treatment, and the treatment selected. In general, superficial bladder cancer, which accounts for 75% of total cases, is highly curable . The other 25% of cases are of higher grade, penetrating, and have been less curable . The survival by stage, given in standard textbooks:

Note that the above survivals include death from all causes in bladder cancer patients, including heart attack, accidents, other cancers, etc. Many bladder cancer patients are elderly and have other medical ("co-morbid") conditions. Furthermore, many patients live high quality lives with incurable bladder cancer, if the symptoms are properly treated ("palliation"). An important consideration is whether the patient keeps their bladder or not.Moreover, as will be seen, the latest therapies appear to boost the above survival rates, while increasing the chance for preserving the bladder.

What is the Conventional Treatment for Bladder Cancer?

This is different depending upon whether the cancer is superficial or invasive.

Superficial Bladder Cancer Options:

1) Trans-Urethral Resection of the Bladder ("TURB") means going in with a cystoscope equipped with a clipper, visualizing the tumor in the bladder, and cutting it out. The patient is carefully monitored afterward for any regrowth of the cancer. The "TURB" procedure may be repeated several times if the disease comes back.Although 90% of superficial tumors are controlled by TURB, they come back 80% of the time! Therefore the 5 year survival with TURB alone is only 60%, so it is not recommended to be used alone, except perhaps as initial therapy for the very smallest disease.
2) Intravesical Chemotherapy means instilling chemicals directly through the urethra, and into the bladder.This may be done after TURB as "adjuvant" (meaning "extra") therapy to help keep the cancer from returning. Various chemicals have been tried, including Thiotepa, Adriamycin, Mitomycin-C, and Cyclophosphamide. Used alone, Intravesical Chemotherapy has only resulted in 60% survival at 5 years (similar to TURB alone) for superficial bladder cancer. If given after TURB, average survival is boosted to 80% . As the chemotherapy is given into the bladder, and not the bloodstream, many of the usual side-effects of chemotherapy (nausea, hair loss) are avoided. This is very useful for treating superficial cancer in the heads of polyps too.

What is the Latest, Effective Treatment for Superficial Bladder Cancer?

Cystectomy, "total" or "partial" , means cutting out the bladder. This is a drastic procedure, since the bladder is lost, but it DOES cure superficial cancers. Pelvic surgery of this sort has a 3% death risk, 10% infections, 10% other "perioperative" problems like blood clots or heart attack, and a three week recovery time. After 3 weeks, the tissues are at least 75% back to normal strength, and weight can again be lifted. A new bladder may be formed using a sac of intestine; this is called a Koch Pouch . The patient may need to stick a tube ("catheter") up the urethra each time they need to urinate. Ideally they may regain continence by increasing their intra-abdominal pressure (as in a bowel movement) to empty the pouch.

Radiation Treatments alone have been used for superficial cancer, and the technique will be discussed in detail to follow. Complete resolution is seen in 50% of patients, so 50% relapse also. It isn't recommended alone . This has been gleaned from intensive study of what works and what doesn't. Even though all the treatments below are not available at all centers, they are more likely to be available at large University Academic Medical Centers (e.g. Memorial Sloan Kettering, Johns-Hopkins, UCSF, MD Anderson, Mayo Clinic):

Trans-Urethral Resection of the Bladder ("TURB") is still important to remove the bulk of the tumor, and should be performed by an experienced urologist. It is common to use "regional anesthesia" (spinal anesthesia) which produces complete lower body numbness. Recall that while short-term tumor control is 90%with TURB alone, nearly 80% will recur-- especially if there are multiple or high grade tumors. Thus, TURB should be followed by other therapy.

Intravesical Chemotherapy is the best treatment to follow TURB. Recall that various standard chemotherapy agents have been tried, but interestingly the most effective drug is NOT a usual chemotherapy agent! The most effective agent is BCG. This is an immune-system stimulating vaccine , instilled into the bladder once per week for 6 to 12 weeks. It even reduces cancer invading into muscle; it reduces the need for later bladder removal. It is proven to raise survival in superficial bladder cancer. It is a very safe, effective regimen, and used appropriately after TURB raises 5 year survival to 95%.

Radioactive Radium Implantation in the bladder has been used after TURB to prevent recurrence, and is obviously a highly specialized procedure. It gives over 80% survival free of disease (apparent cure) at 5 years, compared to less than 50% when TURB is used alone. It is a reasonable option to try and save the bladder if the Intravesical Chemotherapy above fails.

Photodynamic Therapy ("PDT") uses a special dye which attaches to cancer cells, then a medical laser light is shone onto the dye, which activates it. The activated dye kills the cancer cells which have absorbed it. PDT is 80% effective at preventing recurrence after TURB, but is only useful for very superficial disease . Any plaque or obstruction will prevent the laser light from properly activating the dye, so any deeper cancer cells will remain untreated. However, photodynamic therapy may be sufficient to kill cancer in pedunculated (stalk- like) polyps, which may be very superficial.

Salvage Cystectomy, that is cutting out the bladder, can be done if the above "bladder sparing" treatment fail. This will still cure the patient about 80% of the time, and a fake bladder (Koch Pouch) can be reconstructed surgically.

What is the Conventional Treatment for Invasive Bladder Cancer?

Recall that about 25% of patients are found to have "invasive disease" when they first come to medical attention. For these patients, more drastic treatment is required.

Total Cystectomy (complete bladder removal) was historically the only initial treatment for invasive bladder cancer, if it had not obviously spread to distant organs. Urologists were the first specialists to see the patient, did the operation, and hoped for the best. It was rare for any other specialist (i.e. Oncologist) to see a patient who still had their bladder, and it still is in most of America. The Urologist standardly removes any suspicious lymph nodes in the pelvis at the time of surgery, and tries to get a "gross total resection" -- that is the removal of all visible tumor. (S)he takes the perivesical fat from around the bladder, and may need to remove portions of the rectum, prostate, uterus or vagina. If the disease is "locally advanced" in the pelvis, the urologist may do an "anterior exenteration" (removing all pelvic organs except the rectum), or even a "total exenteration" (removal of the rectum also, with a colostomy pouch placed on the abdomen). Unfortunately, despite the availability of these drastic procedures, the 5-year survival rate after surgery averaged just 30% .

Radical Radiation Therapy for invasive bladder cancer was used for patients who were not medically operable (e.g. from heart problems) or for those whom the disease was obviously too extensive for curative surgery. Radiation therapy was very seldom used for patients in whom surgery could be done; the results were somewhat poorer for radiation than surgery-- of course, sicker patients and those with greater disease were being radiated . Thus, the effectiveness of radiation was not (until recently) as appreciated as it should have been. As radiation was, as is, useful for invasive bladder cancer, it is discussed in detail.

Like surgery, radiation therapy is a local treatment, but a wider "field" may be radiated than removed surgically. As will be seen, it can be combined with other therapies to increase "local control" of bladder cancer, since return of bladder area diseasehas been a major problem for unsuccessfully treated patients. Radiation Therapy can also help relieve ("palliate") the symptoms caused by distant spread of the disease. Treatment is administered under a "Radiation Oncologist", a cancer doctor who specializes in utilizing radiation. Radiation kills cancer cells by damaging their DNA, they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete.

Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cells can not. Nevertheless, it is important to be as exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells. Particular areas of concern when radiating the bladder include the rectum and small bowel .

To receive therapy, a patient is first seen in "consult" by a radiation oncologist, who reviews the patient's medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a "simulation" . This means the area to be treated is marked out on a replica treatment machine, and films are taken. Some barium contrast material is usually squirted up the patient's rectum, and other contrast may be placed into the penis opening ("urethra") to determine the lowest portion of the bladder ("urethrogram"). Watercolor marks are paintedon the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless.

Information from the simulation and relevant scans is placed into a "treatment planning computer", which generates a"plan" . This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. For bladder cancer, particular attention is paid for how much radiation is going to the bladder, rectum, and small intestine. Often, the beam is aimed from 4 directions (front, back, right and left sides) to uniformly dose the bladder. Higher energy treatment machines (over 15 Megavolts) also help smooth out the dose to the bladder.The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy. The patient then comes in for their "treatment start" . They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by "Radiation Therapists", or "R.T.T's", who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer. The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from different angles. The patient needs only to lie still. Areas that are not to be treated can be "blocked" with special lead-type blocks in the head of the treatment machine. Normally, patients area treated 5 days a week, Monday through Friday, taking only several minutes each day. The usual dose for bladder cancer is 70 Gray (units of radiation) given at 10 Gray per week. If a treatment is missed, it is simply tacked on to the end so full prescribed dose it given. It is common to "cone down""boost" . Be aware that treatment normally covers the major lymph nodes in the pelvis.

Radiation to the pelvis area is painless, the patient does not become "radioactive", nauseated or lose their scalp hair. The patient can usually maintain normal activities, such as working, driving, and intake of alcoholic beverages. The side-effects of External Beam treatments are classified as "acute" (during treatment) or "late"(months to years after treatment). The most common acute symptoms are reddening of the skin in the treatment area, and anal area irritation. After several weeks of radiation therapy, it is common to develop frequent urination and diarrhea as the bladder and rectum (respectively) become irritated. Prescription of soothing steroid suppositories and anti-diarrheal medicine is usually all that's necessary to treat these acute effects; some dietary modification (less fruit and fiber) may also help. There is often a sense of greater fatigue while receiving radiation. As the dose "builds up" with successive treatments, more blood in the urine may be seen. In general, however, radiation treatments are very well tolerated, the expected side-effects are confined to the treatment area, and abate after completion of therapy. Of more concern are possible "late"effects, which tend to be long lasting or permanent if they occur. Specifically, impotence develops in about 50% of irradiated patients, bladder constriction ultimately requiring cystectomy in 10%, chronic diarrhea in 5%, and bowel or urethral obstruction requiring eventual surgery in 5%. Incontinence is rare (2%) as are second cancers caused by radiation (<1%). Giving the treatment as many fractions, instead of in one large dose, helps reduce the incidence of late reactions. The patient returns for follow-up after completion of treatments, seeing both their urologist and radiation oncologist. If all goes well, they are ultimately seen once or twice yearly for routine check. Overall, radiation treatments are safer than surgery. The results of radiation therapy alone for invasive bladder cancer show about 30% of patients surviving 5 years-- which is the same as surgery! This is especially remarkable, as mentioned, since the irradiated patients are often sicker and have more advanced disease than the "surgerized" patients.

There is no question that local radiation is very valuable in relieving symptoms('palliation") of bladder cancer, whether from pain from spread to nerves, bone, or lymph nodes. It can help relief urinary obstruction caused by the tumor, and chronic blood in the urine.It can be used to relieve neurological symptoms from spread to the brain, or dangerous pressure upon the spinal cord from metastasis.Thus, radiation therapy is almost always used in advanced cancer to relieve symptoms, with up to 90% effectiveness.

Chemotherapy alone, or used as adjuvant ("extra") therapy after surgery, has NOT increased survival using conventional agents. While the initial"response" may be encouraging, Transitional Carcinoma of the Bladder becomes resistant to the chemotherapy, and the cancer starts growing again (usually within 6 - 8 months). However, chemotherapy combined with other treatments has shown benefit , as seen below.

What is the Latest, Effective Treatment of Invasive Bladder Cancer?

Bladder Conservation Therapy is the newer approach. This is accomplished by a combination of pre-operative external beam radiation therapy to 64 gray, along with chemotherapy Methotrexate, CisPlatin, and Vincristine. Then any remaining tumor is removed with TURB or a partial cystectomy. This method, also called "pre-operative chemo-radiation" , was pioneered at Harvard University in Massachusetts. It results in complete resolution of invasive bladder tumor in 80% of patients treated in this manner, andover80% of patients maintain good bladder function! The bladder is only removed ("total cystectomy")if the cancer persists.

TURB can be used to remove the gross tumor, followed by radiation therapy to 50 Gray along with "platinum based" (Cis-Platinum or Carbo-Platinum) chemotherapy. This approach has also met with 80% success, and over 80% preservation of the bladder. Even if the cancer recurs, it is usually the non-invasive type and can be treated with further TURB and BCG (see section on superficial bladder cancer).

The idea of both of the above methods is that the bladder can often be saved, with better survival than conventional radical cystectomy. We are treating with both a local therapy (radiation) and systemic therapy(chemotherapy). Surgical "debulking" of the tumor may occur before or after chemo-radiation. The elegant theory behind all this is called"spatial cooperation" - it basically means getting the most impact out of each of our available treatment methods, and leaving no cancer cells anywhere in the body untreated. However, the reality today is still that many patients are treated with conventional "up-front" cystectomy, as the older generation of urologist were taught as standard; thus they have no chance to participate in bladder-preservation trials.

Post-Operative Radiation Therapy means Radiation Therapy after surgery to remove the bladder. This was originally believed to be ineffective, and so was seldom sought by urologists for patients after cystectomy. However, it has now been re-examined, and shown not only to be effective, but even indispensable. Recall that simply removing the entire bladder in patients with invasive disease yields a 5 - year average survival of about30%. When regional Radiation Therapy is added to the pelvis after healing from the surgery, average 5-year survival increases to over 50%! This is crucial news for patients, since (as discussed above) pelvic radiation is generally well tolerated, and now is available at any cancer center. To reduce late effects even further, radiation treatments may be "hyperfractionated" - that is a lower dose given more than once per day (usually twice per day, 6 hours apart). Hyperfractionation (while less convenient that the conventional Radiation schedule) allows a higher total dose to be given for the same or less risk of late side effects as a lower dose with conventional treatment. It is truly unfortunate the the benefits of post-operative radiation were not better recognized sooner, as this fairly simple treatment would have saved upwards of 20% of invasive bladder cancer who succumbed to this disease.

What About Infected, Bleeding Polpys Harboring Bladder Cancer?

Having dysplasic changes in bladder polyps is a risk factor for developing eventual invasive bladder cancer in 36% of patients. If actual "Carcinoma in Situ" (the most superficial actual cancer) is found in bladder polyps, then 83% of untreated patients will progress to invasive bladder cancer. Furthermore, if the polyps remain in place, then 38% of patients will have recurrences after treatment (Reference - DeVita "Cancer" 4th ed. c1994 p. 1054). When the"urothelium" (inner lining) of the bladder is distorted, it may form stalk-like structures("pedunculated"), flat tumors ("sessile") or pit-like indentations("ulcerated") . It becomes difficult to treat infection, or cancer in any of these because of the irregular structure and surface which can hide disease causing cells .Infection itself can cause bleeding, either detectable only on urinalysis ("microscopic") or seen with the naked eye ("gross") .

This bleeding ("hematuria") will usually resolve when the infection is properly treated, in fact simple infection is the commonest cause of urinary tract bleeding! However, if a supervening cancer is present, the issue is complicated by the fact that the only sign of the early cancer may be infection, and the only symptom of that infection bleeding-- so if the bleeding ceases when antibiotics are given, the cancer will probably be missed. This is why it is so important for patients with "recurrent urinary tract infections" not just to be placed on constant suppressive antibiotics, but to have an evaluation of their urinary tract to obviate("rule-out") cancer.This evaluation will include IVP, cytology of the urine to look for cancer cells in it, and cystoscopy with a visualization tube to actually look at the inner surface of the bladder. Any suspicious lesions should be biopsied, and the stalks of pedunculated polyps may be cut with a scissors on the cystoscope.

Once cancer is confirmed or denied, it is appropriate to aggressively treat infection. There is a wide variety of oral antibiotics effective in usual "Lower Urinary Tract Infections" , that is involving the bladder and urethra. If an "Upper Urinary Tract Infection" exists, this means the ureters or kidneys have become infected ("pyelonephritis") and this usually requires intravenous antibiotic therapy while hospitalized. Pyelonephritis is usually caused by multiple bacteria, unlike simple "cystitis" (bladder infection) which is ordinarily caused by a single bacteria. A Kidney infection usually manifests as high fever with shaking chills, pain in the flank, and blood in the urine. Regular Cystitis has a low fever if any, dull pain above the pubic bone, frequency and irritation while urinating. The way to determine which antibiotic to use is to do a "culture and sensitivity" on an uncontaminated ("clean catch") urine specimen.

When over 100,000 colonies per mililiter of bacteria grow on the culture dish, this is a urinary tract infection. Urine is not usually completely sterile, since bacteria from the stool and skin get into the opening ("meatus") of the urethra and migrate up into the bladder to "colonize" it. Only when these bacteria start growing out of control does an actual clinical"infection" result. Many simple urinary tract infections are caused by the most common bacteria in the stool,E. Coli. These tend to be sensitive to Ampicillin or Sulfa drugs like "Bactrim" and "Septra". If the bacteria become resistant to these, an excellent drug is "Ciprofloxacin" for sterilizing the urinary tract. It is usually taken as a 500 mg. tablet twice per day. However, just like urinary tract infections are more likely to arise in an irregularly lined bladder, they are also harder to treat, and will require repeat testing of the urine to know they are vanquished. Nonetheless, occasional bacteria may hide in irregular polyps and cause the infection to recur. The best way then to treat both infection and cancer in polyps is to remove them . This will take care of superficial cancer, infection, and the bleeding problem all with one therapy - cystoscopic surgery. This can be done under either general or spinal anesthesia, usually as an outpatient procedure.

It may take several days for the operative blood in the urine to clear. Any suspicious area in the bladder, or area close by a superficial cancer, should be biopsied. If Carcinoma in Situ is detected in the neighboring urothelium, or there is any question that the cancer removal was incomplete, BCG instillation to irrigate the bladder should be done. (see section on Latest Effective Treatment for Superficial Cancer) The amount of BCG which will be absorbed into the bloodstream should not have side effects, it is primarily an immune system stimulant. If invasive cancer is found, the patient should generally NOT get an immediate bladder removal ("cystectomy"), but look into the methods discussed in "Latest Effective Treatments for Invasive Cancer". Antibiotics after the operation can be appropriate to prevent infection in the traumatized bladder lining. It is mandatory that whatever the treatment selected, close follow up be done afterward to detect any possible recurrence of cancer expediently. In general the results, as above, for bladder cancer should not be made worse by polyps, as long as they can be properly removed.

What About Advanced Bladder Cancer?

When bladder cancer is stage IV, or "D" , the most advanced type with distant disease spread through the body,the objective is no longer cure but palliation (meaning relief of pain and other symptoms). The patient should always be made as comfortable as possible, and narcotic medicines like morphine (which Osler called "G-d's own medicine) should never be withheld for fear of causing "addiction". Using "Fentanyl Patches"applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, "loss" of narcotics, and smoothing out the dosing for less disturbing "highs and lows". Importantly, Radiation Treatment can help pelvic pain, urinary obstruction, bleeding and bone pain in over 80% of patients. It is also useful for reducing the symptoms, and even extending survival, in patients with spread to the brain. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. Any patient with bladder cancer who experiences new weakness of the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these symptoms . Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression". If this is caught early, and treatment is given, permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms of paralysis once they have set it, however, so quick recognition is essential.

As mentioned,radiation treatment can be very helpful for metastatic bladder cancer. A relatively new method of radiation for spread to the brain (one of the most common areas of spread) is "Stereotactic Radiosurgery", where multiple beams of convergent radiation are aimed onto the area(s) of spread in brain, in a single painless session of one afternoon. This is usually followed by 10 to 20 treatments with conventional "External Beam" radiation. The advantage of Stereotactic Radiosurgery is that it can give a very high dose of radiation to areas of brain metastasis, and possibly enhance survival for these patients, without the risk of an open brain surgery from a neurosurgeon.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and "strontium-89". Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseants are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves can usually afford relief, to this small population of patients. Committing suicide because of unrelieved pain should never be necessary with pain science today.

The patient with newly diagnosed bladder cancer should not rely on any one therapy, but instead should use acombination approach to maximize the chance for success Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy that you believe in, a program of spiritual renewal, "mind over cancer', nutritional therapy and exercise. Keep the most positive attitude possible-- research has shown this to be an important factor in survival. CancerAnswers has a transcript available on reasonable alternative treatments which you can order through our web-site . Using a true"multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and certainly improve the current quality of life.

In conclusion, new techniques utilizing surgery, radiation therapy and chemotherapy are showing better survival rates than ever before for bladder cancer. If cure is the objective, consider getting treatments at a University Academic Center and joining ongoing research trials which offer the latest therapies. The National Cancer Institute keeps a listing of open cancer trials on their website (they change frequently). Especially look for ones listed as "Intergroup" studies, or in conjunction with the Radiation Oncology Therapy Group("RTOG") . The future has never looked brighter for bladder cancer patients