Urinary Bladder Cancer – Risk Factors, Symptoms, Investigations, Staging, Treatment

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How a Patient with Bladder Cancer Presents?

To further understand the disease in a better way, have a look at the video below where CancerBro meets Mr. Blake who has recently been diagnosed with bladder cancer.

We will meet Mr. Blake today, who has recently been diagnosed with bladder cancer.
Mr. Blake had difficulty and pain in passing urine for the last few days and recently, he also noticed reddish discoloration of urine. He also had increased frequency of urination and had to pass urine several times a day.
For these complaints, he consulted a doctor. After complete workup, he was diagnosed to have cancer of the urinary bladder. And was admitted to the hospital for treatment, let us meet him.
Cancerbro: Hi Mr. Blake, how are you feeling now?
Mr Blake: CancerBro, I was very worried when I was diagnosed with bladder cancer, but after talking to you, I am feeling a bit relaxed.
CancerBro: Okay Mr. Blake, please tell me how old are you and where are you from?
Mr. Blake: I am 70 years old and I am from the USA.
CancerBro: What work do you do Mr. Blake?
Mr. Blake: I am a worker in the dye industry.
CancerBro: Are you addicted to smoking?
Mr. Blake: Yes CancerBro, I smoke about a pack daily for almost the past 10 years.
CancerBro: Do you have a history of cancer previously, and received any form of treatment for the same?
Mr. Blake: No this is the first time.
CancerBro: Did anyone else in your family had been diagnosed with any cancer previously?
Mr. Blake: No CancerBro, no one had cancer in my family earlier.
CancerBro: Okay Mr. Blake the bladder cancer patient, thank you very much. I think you people must have got an idea of how a patient of bladder cancer presents, and what are the risk factors for the same.
What are the Bladder Cancer Risk Factors?

Whites are about twice as likely to develop bladder cancer as African Americans. Asian Americans and American Indians have slightly lower rates of bladder cancer.
It is more commonly seen in the elderly as the risk of bladder cancer increases with age.
Also, it is more common in men than in women.
Smoking is one of the most common risk factors for bladder cancer, and the incidence increases with the intensity and duration of smoking.
Exposure to industrial chemicals like aromatic amines, used in dye industry can cause bladder cancer.
The risk factors are occupational exposure to organic chemicals used in rubber, leather, textile, and paint industries.
Heavy exposure to dyes in painters, printers, and machinists also predisposes to bladder cancer.
Previous history of cancer treatment with certain chemotherapy agents or radiation may also predispose to bladder cancer.
Previous history of bladder cancer in the family may increase the risk in other family members.
Other probable causes of bladder cancer are repeated bladder catheterizations, Schistosoma hematobium infection, and recurrent UTIs.

breast cancer risk factors

What are the Symptoms and Signs of Bladder Cancer?

Most common symptoms are reddish discoloration of urine due to blood, increased frequency of urination, painful or burning urination, or weak urinary stream.

Less commonly, it may cause lower back pain, bone pain, or feet swelling.

So these were the symptoms of bladder cancer. These symptoms if kept in mind may help to diagnose the disease at an early stage before it becomes very advanced.

Presence of one or more of above symptoms may require further investigations to diagnose and stage the disease.

bladder cancer symptoms infographic

What are the Symptoms of Advanced Stage Bladder Cancer?

Symptoms of advanced disease may be caused due to local involvement of nearby structures and metastasis to distant sites. Local spread may cause:

  • Difficult and painful urination
  • Increased frequency of urination
  • Reddish urine

Distant spread may cause:

  • Pain in the bony sites
  • Abdominal distension and/or pain
  • Breathlessness, cough, chest discomfort
  • Jaundice, pruritus

What are the Investigations for Diagnosis and Staging of Bladder Cancer?

Urine analysis is a useful investigation to diagnose bladder cancer. It helps in detecting the presence of blood, malignant cells, and tumor markers in urine. The next important investigation for the diagnosis of bladder cancer is cystoscopy.
cystoscopy In this technique, a hollow tube called a cystoscope which is fitted with a camera is inserted into the urethra and is slowly advanced into the bladder. It helps to confirm the presence of a bladder tumor and see it’s number, location, and extent. Also, it helps in transuretheral resection of bladder tumor which is both, diagnostic as well as therapeutic.
cancer containing superficial layers are removed

As you can see in this figure, only cancer containing superficial layers of the bladder is removed, without damaging the deeper layers.

The next imaging modality used for diagnosis of bladder cancer is Intravenous Pyelogram. In this technique, a dye is injected into the arm vein and then a series of X-ray pictures are taken of the urinary tract.
In some cases, we may require a Retrograde Pyelogram in which a dye is injected into the ureter with the help of cystoscope, followed by a series of images.
Pyelogram may be complemented with other imaging modalities, like CT scan or MRI, which help in better delineating the urinary tract.
Also, CT scan or MRI of the abdomen and pelvis helps to understand the local extention of the tumor to other structures and the involvement of regional lymph nodes. It also helps to diagnose the metastatic involvement of other structures.
Imaging of the chest with X-ray or CT scan may be required if clinically indicated. Also, a bone scan may be done if there is a clinical suspicion of bone metastases.
bladder cancer investigations infographic

What is TNM staging for Bladder Cancer?

So after discussing this normal anatomy of the bladder, let’s have a look at the T-staging for bladder cancer. Tis is the carcinoma in situ which is a flat tumor limited to the epithelium.

Tis - carcinoma in situ And Ta is the papillary tumor which is limited to the epithelium.
Ta - papillary tumor Both Tis and Ta are the non-invasive sub-types of bladder cancer. When the tumor infiltrates into the lamina propria it is called T1.
T1 - infiltrates into the lamina propriaWhen it infiltrates into the inner muscle layer, it is called as T2a.
T2a - infiltrates into the inner muscle And T2b when it infiltrates into the outer muscle layer. Till T2 the tumor is limited to the bladder wall, but when the tumor infiltrates through the bladder wall to involve the perivesical tissue it is called as T3 disease.
t3 - infiltrates to perivesical tissue And in T4 disease, the tumor infiltrates through the bladder wall to involve the adjacent structures. It may extend downwards to infiltrate prostate gland in male, as you can see in this figure.
t4 - prostate gland involvementWhereas in females, it may extend posteriorly to involve the uterus or vagina.
t4 - extends to uterus or vagina It may also extend laterally to involve the pelvic or abdominal wall.
t4 - extends to involve the pelvic or abdominal wall T Staging for bladder cancer can briefly be summarised in the figure below.
urinary bladder cancer T staging infographic
Now, let’s come to the N staging or the nodal staging. This figure shows the pelvic and iliac group of lymph nodes which are the regional lymph nodes for the bladder.
N staging Depending upon the number and location of the lymph nodes involved, it can be N1, N2, or N3.Now let’s come to the M staging or the metastatic staging for the bladder cancer. Distant metastases from bladder cancer may occur to the bones. Or to the liver in the form of multiple nodular deposits.
metastasis to liverIt may also spread to one or both the lungs as seen in this figure.
metastasis to lung Or to the peritoneum in form of multiple peritoneal deposits.
metastasis to peritoneum   The image below summarizes the bladder cancer staging.

urinary bladder cancer N and M Staging Infographic

T Staging

Ta  – Non-invasive papillary carcinoma also known as the papillary urothelial neoplasm of low malignant potential (PUNLMP)

Tis  – Carcinoma in situ (Flat tumor; Pre-cancerous or cancer cells present only in the superficial layer of bladder mucosa)
T1  – Tumor invades lamina propria (subepithelial connective tissue)
T2a  – Tumor invades the inner muscular layer (superficial muscularis propria)
T2b  – Tumor invades the outer muscular layer (deep muscularis propria)
T3  – Tumor invades the perivesical tissue (fatty tissue around bladder)
T4a  – Tumor invades the surrounding structures like prostate, seminal vesicles, uterus, vagina

T4b – Tumor invades the pelvic wall or abdominal wall

N Staging

N1 – Tumor has spread to one regional lymph node in true pelvis

N2 – Tumor has spread to multiple regional lymph node in true pelvis

N3 – Tumor has spread to common iliac lymph nodes

M Staging

M1a – Tumor spread to lymph nodes beyond common iliacs (non-regional)

M1b – Tumor spread to one or more distant organs such as lungs, bones, liver, peritoneum, etc.

What is the Treatment of Localised and Locally advanced Bladder Cancer?

We will first discuss the treatment for Localised bladder cancer. In this technique, a hollow tube called a cystoscope which is fitted with a camera is inserted into the urethra and is slowly advanced into the bladder. It helps to confirm the presence of a bladder tumor and see its location, number, and extent. Also, it helps in transurethral resection of bladder tumor which is both diagnostic and therapeutic.
transurethral resection of bladder tumor As you can see in this figure, only cancer containing superficial layers are removed, without damaging the deeper layers.
cancer containing superficial layers are removed This is carcinoma in situ which is a flat tumor, limited to the epithelium. Tis - carcinoma in situ Intravesical chemotherapy should be given in all cases of This disease. As you can see in the figure, in this procedure the chemotherapy drug is directly instilled into the bladder, with the help of a catheter. chemotherapy drug instilled into the bladder And Ta is the papillary tumor which is limited to the epithelium. Ta - papillary tumor For Ta disease also, intravesical chemotherapy may be given. But in some cases, intravesical chemotherapy may not be required, when we can keep the patient under observation. When the tumor infiltrates into the lamina propria, it is called as T1. T1 - infiltrates into the lamina propria For T1 disease, the treatment depends on whether the tumor is low grade or high grade. Intravesical chemotherapy is the treatment of choice for low-grade tumors.
Whereas, for high-grade tumors, the preferred modality of treatment is cystectomy or surgical resection of the bladder. When it infiltrates into the inner muscle layer, it is called as T2a. And T2b, when it infiltrates the outer muscle layer.
T2- tumor infiltrates into the muscle layer For T2 disease, Cystectomy and chemotherapy if preferred. But for non-cystectomy candidates, combination of chemotherapy and radiation therapy may be used.
localised bladder cancer treatment infographic Till T2, the tumor is limited to the bladder wall. But when the tumor infiltrates through the bladder wall to involve the perivesical tissue, it is called T3. t3 - tumor infiltrates into the perivesical tissue And in T4 disease, the tumor infiltrates through the bladder wall to involve the adjacent structures. It may extend downwards to infiltrate prostate gland in males, as you can see in this figure. T4 - tumor infiltrates into prostate Whereas in females, it may extend posteriorly to involve the uterus or vagina. t4 - extends to uterus or vagina
For T3 disease, and selected patients of T4 disease, as discussed above, with nodes negative, the preferred modality of treatment is cystectomy, with chemotherapy, which may be given before or after surgery.
But for non-cystectomy candidates, in which we are not planning surgery, a combination of chemotherapy and radiotherapy may be used.
locally advanced cancer treatment
The tumor may also extend anterolaterally, to involve pelvic or abdominal wall.
t4 - extends to involve the pelvic or abdominal wall This figure shows the pelvic and iliac group of lymph nodes, which are the regional nodes for a bladder. Depending upon the number and location of the nodes involved, it can be N1, N2 or N3.
regional nodes for bladder

In selected patients of T4 disease, with abdominal or pelvic wall extension, and any patient with the node-positive disease, the preferred modality of treatment is chemotherapy, with or without radiation therapy. And further therapy maybe decided to depend upon the response to initial treatment.

What is the Treatment for Metastatic Bladder Cancer?

Now let’s come to the treatment for metastatic bladder tumor. Distant metastasis from bladder cancer may occur to the bones. Or to the liver in form of multiple nodular deposits.

metastasis to liver   It may also spread to one or both the lungs as seen in the figure.
metastasis to lung Or to the peritoneum in form of multiple peritoneal deposits.
metastasis to peritoneum Chemotherapy or immunotherapy is the mainstay of treatment for metastatic disease. But other modalities like surgery, radiation therapy, or bone-directed therapy may be used for palliation or relief of symptoms.
metastatic cancer treatment
Always remember that metastatic disease is not generally curative. So the intent of the treatment is a prolongation of life, reduction of symptoms, and improvement in the quality of life of the patient.

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