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Bladder Cancer – Watch Your Pee

Bladder Cancer Treatment and Surgery in India

What is bladder cancer?

Bladder cancer is the second most common urologic malignancy worldwideand also the fourth most common malignancy in men and thirteenth most common malignancy in women of United Kingdom. The incidence seems to be higher in developed countries than developing countries and twice more frequently in whites than the African-Americans. Peak incidence is seen between 60 and 70 years of age. It is estimated that more than 500,000 of the people in US are suffering from different stages of bladder cancer. Bladder cancer is usually suspected by the common presenting symptom of micro- or macroscopic hematuria.It represents a diverse diagnostic pathologyranging from the classic picture of urothelial carcinoma on one end of the spectrum to the rare morphologic variants such aspure squamous cell carcinoma and small cell carcinoma. High risk patients might require lifelong surveillance. The unique properties of the bladder make it suitable for local drug administration.Though 70-80% of patients undergo local surgical removal for non-muscle invasive bladder cancer approximately half of the cases eventually present with metastatic disease. Muscle-invasive bladder cancer has a more complex presentation and open radical cystectomy is the gold standard for surgical management. Complex involvement of the urogenital tract levies a physical as well as a strong psychological impact on the patient making it one of the most expensive cancers

Causes of bladder cancer

  • Tobacco: The impact of tobacco smoke on bladder cancer has been emphasized by multiple researches over the years. It is one of the most common modifiable risk factor associated with urinary bladder cancer. It is estimated that in Western countries, approximately half of the cases in men and one-third in women are attributable to tobacco. Tobacco contains at least forty types of carcinogens such as aromatic amines such as 2-naphthylamine, 4-aminobiphenyl, benzidine, ortho-tolouidine, which influence the incidence of bladder cancer. A two to three fold increase risk of developing bladder cancer has been reported in subjects smoking ten cigarettes a day. Black tobacco has been found to be more deleterious than blond tobacco. 
  • Combustion gases: Occupational exposure (textile, dye and rubber industries) to industry related gases and chemicals such as polycyclic aromatic hydrocarbon, aromatic amines and benzene compounds; are a source of mixed exposures that have been related convincingly to urinary bladder cancer. However, the results in these cases may also be influenced bydeviating dietary habits and abnormal voiding patterns. 
  • Drugs: Phenacetin may affect the bladder urothelium either directly or indirectly causing adverse changes when used at above optimal doses. Nevertheless the risk of urinary bladder cancer is lower when compared to renal pelvic cancer; possibly due to the inactivation of the responsible carcinogen (phenacetin or a metabolite) in the urine.Chlornaphazine was used for the treatment of polycytemiaverae for a relatively short time and was correlated with a high incidence of bladder cancer in a Danish cohort study. Cyclophosphamide used for treating cancers has also been documented to cause toxic effects on the bladder mucosa. 
  • Ionizing radiation: Radiotherapy of the pelvic region involving the urinary bladder using external beam radiation has been reported to be significantly associated with increased risk of induction of bladder cancer. The best documented cases involved radiotherapy for cervical cancer
  • Infection: Tissue damage induced by the parasite may lead to chronic inflammation predisposing for malignancy subsequently causing an increased cell proliferation associated with an increase in the frequency of random mutations promoting carcinogenesis. Studies have prompted that subjects suffering from bladder infection by Schistosomahaematobium, were at an increased risk for developing mutagenic alterations due to the release of N-nitroso compounds by the microorganism. 
  • Inherited Effect-Modification: Enzyme acetyltransferase is responsible for N-acetylation which in turn is encoded by two distinct genes, NAT1 and NAT2,and thisdetermines whether the individual is a slow or rapid N-acetylator. Data suggest that among cigarette smokers, the ones with relatively slow acetylation showed significantly higher levels of aromatic amines than relatively fast acetylators and acetylation may alter the bladder cancer risk after smoking. 

Signs & symptoms of bladder cancer

  • Hematuria or blood in urine: Micro or macroscopic hematuria is the most common presenting symptom. In most of the cases hematuria is painless and often intermittent which leads to a delay in diagnosis. 25% of adult patients presenting with gross hematuria develop bladder cancer. 17-18.9% of the patients present with macroscopic hematuria, 4.8-6% present with microscopic hematuria and 0.19%-21% present with asymptomatic hematuria. 
  • Voiding dysfunction: It is the direct effect of mechanical obstruction of the lower urinary tract, leading to an increase in the contact time of the potential carcinogens present in urine with the bladder urothelium. A minimum of 7–10 voidings other than those following vigorous physical or sexual activity or prolonged recumbencymay need to be tested. 
  • Urinary hesitancy: It is the delay between making an effort to urinate and the beginning of actual flow of urine leading to a high intravesical pressure. Urine hesitancy leads to higher volume of post-void residual urine and has been reported in approximately 50% of men. 
  • Bladder irritability:Burning sensation on urination
  • Urinary frequency: Frequent urination especially at night
  • Urine urgency: Constant need to but unable to urinate
  • Dysuria: Pain or discomfort on urination

Diagnosis of bladder cancer

  • Dipstick Hematuria Testing: It is an inexpensive technique to assess micro-hematuria in freshly voided urine and has a sensitivity of 0.91 and a specificity of 0.99. It can be done in the physician’s office or even by the patient at home after some training. However, many of the adult population exhibit micro-hematuria though they do not have bladder cancer. 
  • Urine cytology: It is frequently used to assess malignant, suspicious, or atypical cells in voided urine samples. It has a high specificity of 95-99%, yet it has a low level of sensitivity of approximately 34%, however it can be as high as 80–90 % for high-grade disease. It is widely accepted as a clinical tool fordetection of bladder transitional cell carcinoma. Urine cytology is a simple, non-invasive and cost-effective method and is recommended for all patients with risk factors for urothelial carcinoma.
  • Ultrasonography: It is primarily used to evaluate the renal parenchyma. It is a patient-friendly diagnostic method which is cost-effective, easily accessible, requires no patient preparation, and omits the hazards of radiation exposure. Newer contrast-enhanced techniques can improve its diagnostic efficacy.
  • Intravenous pyleography (IVU): Plain radiography is insignificant for the detection of bladder cancer and is limited to findings of calcifications. The addition of intravenous contrast to plain radiography i.e. IVU makes it a valuable tool for the evaluation of the urothelium, and identify filling defects within the bladder. An intravenous contast media is injected into the body and its course through the urinary system is traced via subsequent radiography and tomography. 
  • Computed Tomography (CT): Multidetector row CT, is presently the most widely used imaging modality for the detection of bladder cancer. CT urography is the imaging modality of choice in patients scheduled to undergo TURBT as it permits evaluation of both the renal parenchyma and the urothelium. CT is faster and more informative than IVU but is associated with significantly more radiation exposure. 
  • Magnetic resonance urography (MRU): It demonstrates a suspectable bladder tumor as an area of high signal intensity in contrast to the urine and the bladder wall. On T1-weighted images, urine or fluid is projected as region of low signal intensity making the bladder appear hypointense, whereas on T2-weighted images, fluid emits signals of high intensity.
  • Fluorescence In Situ Hybridization Assay (FISH): Chromosomal aneuploidy and loss of mutated cells in voided urine can be analyzed by FISH which is a laboratory multi-target essay. It has an overall sensitivity of 0.71 in subjects with a previous history of bladder cancer contrary to a specificity of 0.95 in healthy volunteers. Associated disadvantage is the considerable higher cost.
  • ImmunoCyt Test: It is an immunological test incorporating fluorescent labeled antibodies to identify bladder cancer markers in exfoliated cells in the urine. It is an FDA-approved test to be used in conjunction with cytology for the surveillance of bladder cancer and not for detection. It exhibits a sensitivity of 0.86 and a specificity of 0.79.
  • Bladder Tumor Antigen (BTA): It is a laboratory immunoassay of the voided urine used for the quantitative detection of complement factor H and related proteins. It has asensitivity of 0.71 and a specificity of 0.73. It is better utilized for detection of tumors with higher grades and higher stages.
  • Positron Emission Tomography (PET) for muscle invasive bladder cancer: PET is a functional study that detects the uptake of radio-isotopes by metabolically active cells in the body, such as tumor cells. It has reported a sensitivity of 67 %, specificity of 86 %, and accuracy of 80 % for staging of urothelial carcinoma.

Types of bladder cancer 

  • Non-invasive urothelial neoplasms: Based on the risk of recurrence and progression, these neoplasms can be further subdivided into:
    • Papilloma, which isessentially normal urothelium that lacks cellular atypia.
    • Papillary urothelial neoplasm of low malignant potential (PUNLMP), which shows aurothelium with markedly increased thickness.
    • Low-grade papillary urothelial carcinoma (LGTCC)shows a thickened urothelium with hyperchromatic nuclei and few mitotic figures.
    • High-grade papillary urothelial carcinoma (HGTCC) shows marked architectural disturbances.
  • Invasive urothelial carcinoma or transitional cell carcinoma: Accounts for more than 90% of bladder cancers. Histologically it shows invasive nests of nondescript urothelial cells showing minimal to marked nuclear atypia. Variants are urothelial carcinoma with squamous differentiation which accounts for approximately 3–8% of all malignant bladder tumors, urothelial carcinoma with glandular differentiation accounting for 1% of all bladder tumors, small cell carcinoma that accounts for 0.7% of bladder cancers, nested, microcystic, urothelial carcinoma with small tubules, urothelial carcinoma with rhabdoid features, lipoid rich or glycogen rich, and undifferentiated forms. 
  • Non-urothelial bladder cancer form:  Conventional urothelial carcinoma occurring concurrently with a variant, then the carcinoma is considered to be urothelial in nature.

Stages of bladder cancer:

  • pTx: Insuffiecient specimen or cautery artifact
  • pT0: Non-invasive disease; often employed after neoadjuvant therapy 
  • pTa: Non-invasive high-grade papillary urothelial carcinoma
  • pTis: Flat Carcinoma In Situ (CIS)
  • pT1: Invasion into the lamina propria involving the fibrovascular core of the papillary lesion
  • pT2: Invasion into the muscularispropria or involving the detrusor muscle
  • pT2a: Invasion of inner half of muscularispropria
  • pT2b: Invasion extends beyond inner half of muscularispropria
  • pT3: Invasion into the perivesical fat; performed selectively on cystectomy samples
  • pT3a: Microscopically visible invasion
  • pT3b: Macroscopically visible extravesicular mass
  • pT4: Invasion into adjacent organs
  • pT4a: Invasion into prostatic stroma or uterus or vagina
  • pT4b: Invasion into pelvic or abdominal walls

Treatment procedures for bladder cancer

  • Treatment of bladder cancer varies between conservative treatment such as bladder biopsy, transurethral resection of bladder tumor, partial cystectomy and radical treatment such as radical cystectomy, pelvic exenteration. 
  • Transurethral resection of bladder tumor (TURBT): It’s the treatment of choice for most of the localized superficial bladder tumors. The first step is panendoscopy wherein the entire urethra, the prostate, and the entire bladder mucosa are surveyed via a wide angle lens. A continuous flow resectoscope sheath allows safe resection of the tumor associated with the mobile portions of the bladder wall while constantly maintaining the bladder volume. In case of high grade tumors, muscle is also resected. Lasers such as neodymium:YAG laser can also be used for tumor ablation. 
  • Intravesical chemotherapy: It is indicated in patients who are at high risk of recurrence and for tumors that are confined to the bladder mucosa.  T1 tumors are best treated with mitomycin C or doxorubicin. BCG or bacillus of Calmette and Guerin is also a powerful therapeutic agent used against superficial bladder cancer cases especially the aggressive ones. Prior to intravesicular therapy the patient needs to be dehydrated, a diuretic can be taken later in the day. 
  • Preoperative radiation therapy: It is indicated in cases of invasive bladder cancer. It reduces the primary bladder tumor burden andmay make radical cystectomy technically easier.
  • Radical cystectomy: It is the treatment of choice for high grade invasive bladder tumor. Radical cystectomy involves the resection of the pelvic-iliac lymph nodes along with the pelvic organs anterior to the rectum: the bladder, urachus, prostate, seminal vesicles, and visceral peritoneum in men; the bladder, urachus ovaries, fallopian tubes, uterus, cervix, vaginal cuff, and the anterior pelvic peritoneum in women. 
  • En bloc radical cystectomy and pelvic-iliac lymphadenectomy: Radical cystectomy with en bloc pelvic lymphadenectomy is effective in local control of the tumor. During en bloc the perivesical fat, pelvic and iliac lymph nodes are also removed with the specimen. Firstly a careful bimanual examination is preformed followed by a transurethral resection or deep biopsy of the tumor under general anesthesia determine of depth of tumor invasion.Patient is advised a clear liquid diet until midnight, at which time the patient takes nothing per mouth.

Complications associated with treatment of bladder cancer

  • Metabolic acidosis: Symptoms are fatigue, nausea, anorexia, and vomiting. It can be relieved by ingestion of bicarbonates. 
  • Urinary incontinence: Approximately 90 % of patients may develop daytime continence and 80 % might develop nighttime continence by 18 months. It can be relieved by timed voiding.

Risk factors for bladder cancer

  • Genetics: A family history of urinary bladder cancer has been reported to pose anincreased disease risk probably due to the shared life habits.
  • Age: Incidence of bladder cancer increases with age with peak incidence at the seventh to eighth decade of life. 
  • Gender: Males are more predisposed to developing bladder cancer than women in ratio of 3:1.
  • Race: In the United States, bladder cancer has shown to affect twice as many whites than blacks.
  • Geographical distribution: In United States, bladder cancer has shown a decrease in incidence at the rate of 0.8% per year. In Sweden, men have shown a decrease in incidence of bladder cancer while women have shown an increase. In Europe and United States, urinary bladder cases were found to be higher in urban than rural areas. 

Am I a Good Candidate for surgical Treatment? 

If you are suffering from urinary urgency but unable to pass urine, experience presence of blood clots in urine, change in color of urine to reddish brown, pain and burning sensation on urination, then it’s time you visit your physician. Following diagnostic tests you will be advised appropriate treatment. A delay of longer than 90 days in surgical intervention if required especially in patients with muscle invasion at diagnosis, can adversely affect the prognosis as the disease progresses to a more advanced pathologic stage.

Recovery time and aftercare

Broad-spectrum antibiotics are to be continued for 24 hours. Patients are ambulated on the first post-operative day and are encouraged to sit in a chair from the night of surgery. On the first post-operative day nothing is to be taken by mouth, on the second day noncarbonated clear liquids are to be taken every 8 hours, followed by unrestricted non-carbonated clear liquids on third day, and finally a regular diet on postoperative from fourth day onwards. Patient is instructed to cycle their pouch by gradually increasing the time interval between urination so as to achieve a full bladder capacity. Practice times voiding of urine guided by an alarm clock. Pelvic floor exercises are to be practiced till complete recovery. 

Success Rate of surgical resection

Randomized trials have reported that 49% of patients treated with transurethral resection alone remained free of recurrence. Following radical cystectomy pelvic recurrences were reported to be less than 10% for subjects with node-negative bladder tumors, and 10%–20% for subjects with resected pelvic nodal metastases and an overall survival rate of 62% at 5 years.  

Benefits of bladder cancer treatment

  • Eradication of existing tumor
  • Prevention of recurrence
  • Halting tumor progression
  • Enhanced survival

Cost comparisons

A transurethral resection might cost up to $3000 while radical cystectomy might cost up to $4900. Prices may vary depending on the stage of bladder cancer at the time of diagnosis, surgical intervention planned, days of hospital admission and expertise of the surgeon. 

Why choose MedcureIndia? 

Urologic diseases are one the most distressing and perturbing conditions affecting the adults. Bladder cancer should be treated promptly following diagnosis for better survival. MedcureIndia aims to make surgical interventions and hospital stays convenient and comfortable for the patient. We provide strategic treatment planning, painless treatment procedures and complete assistance through recovery. With our proficient team of doctors you can be assured of quality treatment and advanced medical care. 

 

FAQ’s -

• How many days do I have to stay in the hospital?

Following a transurethral resection for superficial tumors the patient might be discharged the same day or the next. Complete recovery so as to be able to resume daily activities may take 2-3 weeks. Patient undergoing radical cystectomy might have to stay in the hospital for 4-5 days depending on the stage of bladder cancer. If the patient suffers from additional chronic conditions that complicate the procedure, the surgical intervention will be planned accordingly and may affect the number of days of hospital stay. Complicated cases may take more time for recovery as well. 

Will I be able to urinate normally after bladder surgery?

In patients who have undergone radical cystectomy, a new way for passage of urine is constructed via urostomy. Such patients are instructed to vacatetheirurostomybag periodically or put a catheter into your stoma. Patient is instructed to cycle their pouch by gradually increasing the time interval between urination so as to achieve a full bladder capacity. Practice times voiding of urine guided by an alarm clock. Pelvic floor exercises are to be practiced till complete recovery.

• Does cystectomy affect my sexual life?

Radical cystectomy removes the prostate, seminal vesicles, and visceral peritoneum in men and fallopian tubes, uterus, cervix, vaginal cuff in women. In men, this may lead to inability to produce semen and erection problems. Young men have a tendency to regain their ability to have an erection with time. Women can undergo vaginal reconstruction to make sex more comfortable. Consult your surgeon for newer and better surgical options that spares the reproductive functions postoperatively

• What is the possibility of recurrence of bladder cancer?

Recurrence depends upon the stage of the cancer. Non invasive cancer has a recurrence chance of 20 to 30%.  Invasive cancer have recurrence chance of about 70%. Those having pure “adenocarcinoma” or “squamous cell carcinoma” bladder cancer seem to have a higher chance of recurrence 

• Will I be tested for cancer in future?

Yes. Patient is tested frequently to check the recurrence if any. Though the frequency depends on the stage of the cancer which patient has survived

Can the cancer be diagnosed early?

Yes. Cancers can be diagnosed early if the patient is aware of the warning symptoms and consults doctors in time

• Can cancer be completely cured?

Yes, early detection and proper targeted treatment can completely cure of some cancers. Many cancer patients have returned to their normal life activities after a successful cure.

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