Bladder Cancer

Bladder cancer occurs on the inner lining of the urinary bladder, known as the bladder mucosa, which is only 5-6 cells in depth, but very much exposed to toxins excreted in the urine, which act to cause cell dysplasia and carcinoma. Most bladder cancers are superficial on the mucosal surface, with a low risk of progressing to a muscle invasive or metastatic cancer. These superficial cancers are known as Non Muscle Invasive Bladder Cancer (NMIBC) and comprise 75% of newly diagnosed bladder cancer.

The more serious form of bladder cancer is Muscle Invasive Bladder Cancer (MIBC) which has a high risk for invasion beyond the bladder and therefore requires more aggressive treatment.

A/Prof Peter Royce and Mr Dennis King administer treatment for bladder cancer at Cabrini Hospital Malvern, Cabrini Hospital Brighton, Epworth Eastern Hospital Box Hill and St. John of God Berwick, Melbourne, Australia. We have a special interest and expertise in bladder cancer treatment, using decades of experience, multidisciplinary oncology forums, European Association of Urology Guidelines and the support of our private Oncology Nurse for perioperative patient education and care.

We welcome your enquiries if you or someone you care for, has been diagnosed with bladder cancer.

What Are The Risk Factors For Bladder Cancer ?

Bladder cancer has been associated with exposure to a number of environmental factors. Smoking is the most consistent and common risk factor known to cause bladder cancer.

Association with heterocyclic amines is found in several industries including rubber manufacturing, petrochemical, dyestuffs and textile printing.

There has also been associations with cyclophosphamide exposure, previous pelvic radiotherapy, schistosomiasis infections and chronic bladder infection.

The molecular biology for bladder cancer has been thoroughly investigated, however at this stage molecular testing for DNA or mRNA defects is not at the level of clinical use, so we rely on tumour cytology, histopathology and radiology for selection of appropriate treatment and prognosis.

What Are The Signs & Symptoms Of Bladder Cancer

The most common symptom is the development of haematuria (blood in the urine). This may be either macroscopic (visible to the eye) or microscope (only detected by laboratory testing).

The amount of bleeding is not necessarily proportional to the severity of the cancer, and there are many other causes of blood in the urine. With cancer the bleeding is not always constant and may actually disappear before returning some time later. Hence the presence of haematuria should never be ignored since this may be the only sign of a problem in the urinary tract.

Tumours in the bladder may be found as an incidental finding discovered on Ultrasound or CT scanning or during a Cystoscopy (examination of the bladder with a telescope).

Urine cytology (examination of the urine for cancer cells) may also be performed. This is most useful for detecting high grade bladder tumours.

How Is Bladder Cancer Diagnosed ?

A Cystoscopy needs to be performed with resection of the tumour down to the detrusor muscle of the bladder wall. This procedure is known as TURBT for Trans Urethral Resection Bladder Tumour. The resected material is then removed and sent for histological analysis by an experienced Pathologist.

The EAU Guidelines for TURBT advise En bloc tumour resection using visual enhancement systems, to minimise the risk of overlooking multiple bladder tumours. In specific cases with high grade urine cytology, multiple biopsy of the bladder and prostate urethra is indicated to detect Carcinoma In situ.

Most bladder cancer is a type described as a Transitional Cell Carcinoma, which can be papillary, solid or carcinoma In situ, according to the pattern of tumour growth on the bladder surface.

There are some specific bladder cancer variants which can be present in 6% of bladder tumours, and these variants are more aggressive tumours which need to be recognised and treated with specific chemotherapy and surgery. These are the Micropapillary, Pure Squamous Cell, Pure Adenocarcinoma, Small Cell Carcinoma, Plasmacytoid variants.

Bladder Cancer at Cystoscopy

Transitional Cell Carcinoma is either Low Grade or High Grade and either Superficial or Invasive.

Staging TMN System

Staging reflects the degree of spread of the cancer which has important implications for treatment and overall outcomes.

• T (tumour).
• M (metastatic) spread outside the bladder to other organs.
• N (lymph node involvement).
• Ta involves the submocusa.
• T1 lamina propria invasion.
• T2 Muscle invasion.
• T3 invades the fat surrounding the bladder.
• T4 invasion of adjacent organs.

In general most bladder cancers are superficial (involving the mucosa or submucosa) and have not spread elsewhere. Only 10-20% of superficial cancers progress over time. After resection there is a high risk of tumour recurrence approaching 50%. This can be modified with the use of chemotherapy or immunotherapy (BCG) treatments which are placed in the bladder for a short period either immediately after TURBT, or for a 6 week course starting a few weeks after TURBT.

Intravesical Chemotherapy uses either Mitomycin C or Gemcitabine.

Intravesical Immunotherapy uses BCG (the same attenuated TB vaccine).

Muscle invasive cancers are generally very aggressive and require more urgent treatment using combinations of chemotherapy/surgery or chemotherapy/radiation therapy.

Staging of the cancer is indicated by the Pathologist assessment of the removed bladder tumour from TURBT. In the case of stage T1 tumours, the EAU Guidelines recommend a repeat TURBT to minimise the risk of missing a T2 cancer in the initial TURBT.

Determination of whether the cancer has spread outside the bladder is generally performed for higher risk/invasive cancers and involves the use of imaging techniques such as Computerised Tomography of the chest, abdomen and pelvis, MRI scan of pelvis, FDG PET scan of the body, whole body bone scan.

Treatment For Muscle Invasive Bladder Cancer (MIBC)

Radical Cystectomy

Radical Cystectomy is performed when cancers invade the bladder detrusor muscle wall.

In men the bladder is removed with the prostate, seminal vesicles, adjacent pelvic lymph nodes and if the prostate is involved then the urethra may also be excised. In selected cases the RC may be done with careful dissection and preservation of the neurovascular bundles for erections.

In women the bladder is removed with the uterus, ovaries, anterior vaginal wall and urethra.

Surgical reconstruction to replace the removed bladder then needs to be performed. There are different forms of reconstruction and this can involve either the creation of a conduit or the creation of a neobladder.

• Ileal Conduit - This procedure has been routinely performed since the 1950's. The internal pouch which holds the urine is made from a small portion of intestinal tract. One end is closed with sutures while the other end is attached to skin on the front side of the abdomen. A stoma is the open end of the conduit attached to the skin. An external appliance (urostomy bag) covers the stoma to collect urine. The ureters are implanted into the back of the ileal conduit.
• Catherisable Continent Diversion Pouch - This is a reservoir of bowel with a stoma that is catheterisable for emptying the bladder. The urine is siphoned out of the urinary reservoir with a small catheter every 4-6 hours. The catheterisable pouch may require surgical repair at some point after surgery due to the wear and tear of frequent catheterisation. This type of reconstruction is not performed on patients with a history of bowel disease.

• Neobladder - A neobladder is a new bladder made from 54 cm of small intestine, folded and sutured into a reservoir. This internal (new bladder) is connected to the urethra and ureters.

  We use the Studer Neobladder surgical technique as the preferred option, although there are many variations on the same idea. After this reconstruction the patient needs to relearn how to pass urine on the clock, using straining for abdominal compression of the neo bladder. The advantage is that there is no stoma or urostomy on the abdomen. Some disadvantages of this type of reconstruction are possibility of scar tissue formation at the connection of the urethra and neo bladder and incontinence of urine, particularly at night.

  Some patients will develop metabolic acidosis due to reabsorption of urinary acid from the neobladder, this requires regular monitoring of blood electrolytes, and may require daily oral sodium bicarbonate to restore blood pH balance.

  It is very important to keep the neobladder as empty as possible, so we advise all neobladder patients to learn the technique of Intermittent Self Catheter (ISC).

  ISC is instructed before surgery, in our private rooms with our Oncology Nurse.

  It is also very important to learn Pelvic Floor Exercises (Kegel Exercises) to restore urinary muscle control after RC and Neobladder surgery.

  A/Prof Royce and Mr King have treated men and women with bladder cancer utilising all of these surgical techniques. This includes patients with very complex situations, for example in men after previous prostate radiation or radical prostatectomy for prostate cancer. In women after previous radiation for cervical or uterine cancer. In men and women after previous surgery for rectal cancer. These cases can be surgically very difficult with higher than normal risks for complications, and should only be performed by Urologists with this level of surgical experience.

Neoadjuvant Chemotherapy

Neoadjuvant Chemotherapy is the terminology for administering chemotherapy prior to Radical Cystectomy. Transitional Cell Carcinoma is sensitive to Cisplatin and Gemcitabine which are used in combination for 3-4 cycles of treatment in the weeks before RC.

Carboplatin is a less toxic but less effective drug than Cisplatin, and should not be substituted for the drug of choice.

Neoadjuvant Cis-Gem therapy has been proven in randomised clinical trials to enhance patient survival by 5-10% compared to not having this treatment before surgery. The reason why Cis-Gem chemo improves survival is due to its effective treatment of micro metastases. Surgery is very effective in eradicating cancer in the organs removed ie. bladder and pelvic lymph nodes, but chemo is required to eradicate cancer cells that may be present but not detectable in other sites, such as lungs, liver, bones etc. Neoadjuvant chemo is administered by a Medical Oncologist working in conjunction with the Urologist, after discussion of the patients histopathology, radiology imaging and medical past history at a Multidisciplinary Oncology Meeting.

A/Prof Royce and Mr King both attend fortnightly Urology MDM at The Alfred Hospital, where they are both Consultant Urologists. They work in collaboration with specific Medical Oncologists who understand the EAU Guidelines and best practice for treating MIBC.

You can have Neoadjuvant Cis-Gem at either Cabrini Malvern or Alfred Hospitals, depending on your preference. You may also be asked to participate in clinical trials using the latest innovations in therapy, but there is no compulsion and the choice is always with the patient.

Immunotherapy

Immunotherapy using drugs such as Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab, Avelumab have shown to be effective in 30-54% of bladder cancer which is refractory to Cisplatin, these drugs are known as Immune Checkpoint Inhibitors or PD-L1 inhibitors, and have been used to treat metastatic bladder cancer.

The future of muscle invasive bladder cancer treatment will involve using Immunotherapy and Cis-Gem chemotherapy before surgery, and there are several global clinical trials assessing these various combinations for safety, efficacy and survival.