Bladder cancer is the most common cancer of the urinary system. It is quite common throughout the world with the US alone reporting 79, 030 cases and 16, 870 deaths in the year 2017. In developing nations like India and other countries in South East Asia, this risk is almost twice as high as per review from the PubMed library. This significantly states the need for early diagnosis and treatment.
Risk Factors for Bladder Cancer
Age, Gender and Ethnicity
Older age individuals especially males are generally at increased risk of developing bladder cancer with most of the incidences observed in the 6th, 7th, and 8th decades of life.
Use of tobacco is one of the major risk factors for bladder cancer with the higher risk involved for more amount used over a short duration. Smokers are at 3 times higher risk of developing bladder cancer compared to non-smokers. The incidence increases with the intensity and duration of smoking.
Risk of developing bladder cancer increases in an individual with a history of bladder cancer in first-degree relatives (parents, brother, sister, or child). Previous history of bladder cancer in the family may increase the risk in other family members.
Genetic Cancer Predisposition Syndromes
Following are some examples:
- Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC, generally caused by a mutation in the MLH1 or MSH2gene);
- Cowden disease (caused by a mutation in PTEN/MMAC1 gene); and
- mutations in retinoblastoma (Rb1), SLC14A1 (a urea transporter gene), GSTM1, and NAT2.
Individuals with a personal history of cancer in the lining of any part of the urinary tract are generally at higher risk of developing another cancer.
Higher risk of bladder cancer is also associated with regular exposure to certain chemicals like paint, dye, heavy metals, or petroleum products generally experienced by dyestuffs workers, painters, leather workers, truck drivers, aluminum workers and workers in the dry-cleaning industry.
History of exposure to radiation and treatment with certain drugs like cyclophosphamide, ifosfamide, phenacetin, and pioglitazone is reported to be the independent risk factors for bladder cancer.
Infection with Schistosoma haematobium (a parasitic worm that is prevalent in certain parts of Africa and the Middle East) is associated with an increased risk of bladder cancer.
Exposure to a high level of arsenic or chlorine in drinking water can also increase the risk of bladder cancer.
Chronic irritation of bladder
Chronic irritation by urinary tract infection, kidney/bladder stones, or prolonged use of catheters have also been linked to a high incidence of bladder cancer.
Diabetes mellitus (especially type 2 diabetes), heavy alcohol consumption, high intake of coffee/tea, artificial sweeteners, and low intake of water are some other risk factors postulated for bladder cancer.
Bladder Cancer Symptoms and Signs
But, how will you seek treatment if you don’t suspect bladder cancer in the first place? To meet this gap, we will introduce you to the symptoms of bladder cancer so that you can easily speculate your risk.
Bladder cancer may present with any one or more of the signs or symptoms mentioned below. These may vary depending on the extent of disease, location of bladder tumor, site of metastasis, etc.
Sometimes, other conditions may present in a similar manner. So, it is important to consult your doctor if you notice any of these symptoms and undergo thorough testing.
Early Symptoms of Bladder Cancer
Blood in Urine (Hematuria)
In most cases, haematuria is the first sign of advanced bladder. It may in the form of microscopic or gross hematuria. Microscopic haematuria is the presence of blood in urine, which may not be visible to your naked eye. Gross hematuria is, the presence of blood in your urine, which will be very much visible to the naked eye. It may be in the passage of blood clots in urine in some cases. In other cases, it may simply be seen as change in the colour or your urine to a reddish colour.
The American Cancer Society classified this colour to be ranging from orange or pink to red and dark red, the latter being relatively uncommon.
You must note that you need not wait until you notice blood in your urine each day before suspecting bladder cancer. You may notice it on a day and then may not see it again for months. In most cases, there will be very little to no pain.
Increased Frequency of Urination (Poluuria)
You may feel the urge to feel more often than usual. Maybe at every hour or several times of the day. Further, you may repeatedly wake up at night to urinate or may face difficulty in sleeping because of frequent awakenings due to this desire.
It may be due to the bladder mass obstructing the urine flow causing incomplete emptying of the bladder. It may also be due to urinary tract infection causing bladder irritation leading to frequent passing of urine.
Burning or Painful Urination
Burning urination may be due to urinary tract infections, occuring as a result of long term retention of urine in bladder. This may be associated with increased frequency of urination also.
Painful urination and difficulty in urinating despite the presence of desire to urinate may occur due to bladder neck mass causing obstruction in the flow of urine.
Constitutional symptoms like fatigue, weight loss, loss of appetite and/or diminished desire to participate in daily activities such as going to work, exercise, etc may occur as a result of bladder cancer or coexistent urinary infections.
Symptoms of Late or Advanced Stage Bladder Cancer
Late stages of bladder cancer include cases with locoregional involvement of nearby structures and distant spread of the tumor. In addition to ones mentioned above, these may be one or more of the following-
Heaviness or Pain in Abdomen
Presence of a lower abdominal or pelvic mass, which may or may not be painful may be an indication of bladder cancer that has spread to surrounding areas. Or else, it may occur due to the spread of cancer to lymph nodes in lower abdomen.
Involvement of intestine may cause intestinal obstruction leading to constipation and feeling of heaviness in abdomen or bloating sensation.
Obstruction to the flow or passage of urine may cause bladder fullness that may cause discomfort in the pelvic region. Sometimes, bladder mass close to vesico-urteral junction may cause hydronephrosis and pain in back or loin region.
Spread of bladder cancer to liver may cause jaundice or yellowish discoloration of eyes and/or urine. It may sometimes be associated with pruritus or generalised itching over the body.
Breathlessness or Cough
Breathing difficulty, excessive coughing and/or pain on deep breathing may be a sign of bladder cancer spread to lungs or pleura (causing fluid accumulation around the lungs).
Pain at Bony Sites
Sometimes, spread of bladder cancer to one or more bones may cause pain in back, ribs, etc.
Can Bladder Cancer be mistaken for UTI?
Urinary tract infection is one of the commonest benign differential diagnosis of bladder cancer. As we have already discussed above, early symptoms of bladder cancer such as increased frequency of urination, nocturia, burning sensation during passage of urine are the most common symptoms of urinary tract infections also.
Moreover, microscopic or macroscopic hematuria may also be seen in some cases of UTI.
So, bladder cancer, especially in early stages could easily be mistaken for UTI. A high level of suspicion and adequate diagnostic work-up is very important to differentiate between the two.
Bladder Cancer Diagnosis
When someone is suspected of bladder cancer based on presence of signs or symptoms, certain diagnostic investigations are required to confirm and stage the disease.
These diagnostic tests discussed below help us confirm the presence of bladder tumor, and also other details, like type of tumor, number, depth of invasion, involvement of regional lymph nodes, and spread to distant sites.
All this information helps the oncologist to take an appropriate treatment decision. The infographic below lists some of the investigations.
Urinalysis helps us detect the presence of blood cells (RBCs) in urine. Patients with bladder cancer may have hematuria (blood in urine). It may be grossly visible (macroscopic hematuria) or may be detected only on microscopic examination of the urine sample (microscopic hematuria).
In this test, a urine sample is checked for the presence of abnormal (precancerous or cancerous) cells using a microscope. Presence of abnormal cells may indicate diagnosis of cancer in the urinary tract. Further investigation is required to find the location of the tumor.
Urine Tests for Tumor Markers
With the advancement of science, newer tests are now available to check the presence of certain markers in the urine which may suggest bladder cancer. For example, Telomerase (an enzyme usually found in cancer cells), bladder tumor-associated antigen (BTA), carcinoembryonic antigen (CEA), and NMP22 protein. But these tests are not very reliable and may provide with a supportive evidence of the tumor.
Cystoscopy is a diagnostic technique which uses a cystoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery. This enables to look inside the bladder by passing the cystoscope into the bladder via urethra to determine the presence and extent of the disease. Also, it helps in transuretheral resection of bladder tumor which is both, diagnostic as well as therapeutic.
As you can see in this figure, only cancer containing superficial layers of the bladder is removed, without damaging the deeper layers.
Transurethral resection of bladder tumor (TURBT)
If the abnormal area(s) are observed during cystoscopy, biopsy samples are collected from the abnormal area through a transurethral resection of bladder tumor (TURBT) or transurethral resection (TUR) technique. The tumor along with underlying muscle tissue is removed to check the extent of invasion into the bladder wall. Multiple biopsies may be obtained depending upon the cystoscopy observations. This technique helps in establishing the stage of the disease.
In this technique, various x-ray images are taken of the urinary system after injecting a contrast (dye) into patient’s vein. The dye outlines the complete urinary system on the x-ray images and is excreted in the urine by kidneys. This helps the doctor to examine the urinary tract for any abnormal areas.
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.
CT Scan or MRI
Bladder Cancer Staging
The bladder is an inflatable, hollow muscular organ situated in the pelvis. The main function of the bladder is to store urine until it is excreted from the body through the urethra. In a normal adult, it can hold up to 800 mL of urine.
The walls of urinary bladder consist of mainly three layers: mucosa (made up of transitional epithelium cells), lamina propria (made up of connective tissue), and muscularis propria (made up of 3 layers of smooth muscle fibers).
Staging for bladder cancer is called as TNM staging system. It helps in disease prognostication and choosing an appropriate treatment strategy.
Stage 0 Bladder Cancer
Stage 0 bladder cancer includes cases of TaN0M0 and TisN0M0. This means Tis or Ta disease (as discussed below) without the involvement of regional nodes or distant spread of tumor.
The figure below shows the epithelium, that is the innermost layer of the bladder wall.
Stage 1 Bladder Cancer
Stage 1 bladder cancer includes cases with T1N0M0 disease, that it T1 disease (as discussed below) without involvement of regional nodes or distant spread.
The layer of the bladder wall outside the epithelium is called as lamina propria, as shown in the figure below.
Stage 2 Bladder Cancer
Stage 2 includes cases with T2N0M0 disease, that it T2 disease (as discussed below) without spread to regional lymph nodes or distant organs.
To understand it better, let’s see the layers of the bladder wall first. Outer to lamina propria lies this layer, called an inner muscle layer. And on the outermost aspect lies the outer muscle layer.
Stage 3 Bladder Cancer
Stage 3 tumor can be further classified into Stage 3a and Stage 3b.
Stage 3 includes cases of T3N0M0, T4aN0M0, T1-4aN1-3M0.
Stage 4 Bladder Cancer
Based on the TNM staging discussed above, bladder cancer may be classified into 4 stages as mentioned below.
|0a||Ta N0 M0|
|0is||Tis N0 M0|
|I||T1 N0 M0|
|II||T2a N0 M0 T2b N0 M0|
|IIIa||T3 N0 M0 T4a N0 M0 T1-4a N1 M0|
|IIIb||T1-4a N2-3 M0|
|IVa||T4b Any N M0 Any T Any N M1a|
|IVb||Any T Any N M1b|
Survival Rate/Life Expectancy based on Stage
It is calculated based on whether the disease is Localised, Regional or Dstant.
- Cancer is limited to the bladder.
- 5 year survival 70%.
- Cancer has spread to nearby structures or lymph nodes
- 5 year survival 36%.
- Cancer has spread to distant body parts like lungs, liver or bones.
- 5 year survival 5%.
Treatment for Bladder Cancer
Treatment of bladder cancer depends on the stage, type, unifocal/multifocal, performance status of the patient, along with other factors. But the final treatment decision is taken by the oncologist after clinical evaluation of the patient.
Stage 0 Bladder Cancer Treatment
In intravesical therapy, drug is placed directly into the bladder using a catheter. It can produce local action without affecting other body parts. Drugs like mitomycin, valrubicin, docetaxel, thiotepa, and gemcitabine can be given by this technique. Bacillus Calmette-Guerin (BCG) (a modified tuberculosis bacterium) can also be given by this technique, which acts by activating the body’s immune system to destroy cancer cells. The most common side effects associated with intravesical therapy is irritation/burning in the bladder.
A bacterial vaccine– Bacillus Calmette-Guérin (BCG) (generally used to prevent occurrence of tuberculosis) is used in preventing early-stage bladder cancer recurrence. BCG stimulates the immune cells to attack bladder cancer cells.
Induction intravesical BCG therapy is usually given once a week for 6 weeks. Two or more rounds of BCG induction therapy may be employed with a treatment-free interval of 4 to 6 weeks. Maintenance therapy with a monthly BCG dosing for about 1 to 3 years may be employed in some patients with high risk of disease recurrence.
Stage 1 Bladder Cancer Treatment
Stage 2 Bladder Cancer Treatment
Stage 2 bladder cancer includes cases with T2 disease, without the involvement of regional lymph nodes or distant spread of the tumor.
Stage 3 Bladder Cancer Treatment
Stage 3 includes cases of T3N0M0, T4aN0M0, T1-4aN1-3M0.
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.
Stage 4 Bladder Cancer Treatment
Chemotherapy drugs that are part of bladder cancer treatment regimens are-
Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, and Avelumab. These immune-checkpoint inhibitors have been approved as the second-line treatment of locally advanced or metastatic urothelial cell carcinoma (most common type of bladder cancer) that has progressed on or after platinum-based chemotherapy. These agents can be employed for the treatment of patients who have progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. The PD-L1 expression levels estimation is not a pre-requisite for employing these agents as second-line treatment.
Best Bladder Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating bladder cancer patients. He has treated bladder cancer patients with Intravenous and Intravesical Chemotherapy and Immunotherapy . He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Cystoscopic Biopsy, Transurethral Resection of Bladder Tumor, Intravenous Pyelogram, Urine Cytology, etc. Other treatment facilities for Bladder Cancer available are Radical Cystectomy, Partial Cystectomy, Radiation Therapy etc.
Call +91 9686813020 for appointment.