Introduction
The urinary bladder is a hollow organ in the pelvis that stores urine for a temporary period until it is passed during urination. Bladder cancer is a common cancer affecting the urinary system; and bladder is the most commonly affected cancer site in the urinary system. Most of the bladder cancers originate at the urothelium, which is a layer of mucosa lining the bladder (cancer.net). It is very common in the regions of the Americas, Europe, and Asia. Squamous cell carcinoma is the second most common carcinoma. Approximately, 2% of bladder cancers are adenocarcinomas and 0.3% to 0.7% are small cell carcinomas (Medscape).
Epidemiology
In the year 2012, there were 73,510 estimated cases of bladder cancer with 14,880 as the estimated mortality rate associated with bladder cancer. It is the fourth most common cancer in men. The incidence is almost double in white men as compared to black men in the US, but the prognosis is worse in blacks. Women too have a worse prognosis then men (Cancer.Net).
Medical Illustration
Figure shows the median sagittal for male and female body. The bladder wall with layers is shown. Most bladder cancers arise in the innermost layer – the urothelium. Adapted from:Cancer.Net. Available at: http://www.cancer.net/sites/cancer.net/files/styles/medical_illustration_web/public/bladder_print.jpg
Etiology
Approximately, 80% of bladder cancers are due to environmental conditions. Surprisingly, smoking is the most common cause. Smoking duration, frequency, and intensity are all directly proportional to its risk. Smokers have a 2.6 times higher risk of developing bladder cancer as compared to non-smokers. Harmful agents found in cigarette smoke like nitrosamine, 4-aminobiphenyl, and 2-naphthylamine are known to be the culprits behind development of the cancer (Medscape).
Some other causes are occupational exposures to aromatic amines, diesel exhaust, and petroleum products. Persons working as beauticians, dental workers, painters, or dry cleaners etc. are at an increased risk of developing bladder cancer (Medscape).
People living in urban regions are likely to be affected due to exposure to carcinogens. In most of the underdeveloped countries, an infection with Schistosoma haematobium causes the squamous cell type of cancer. It is also seen to run in families although convincing evidence does not exist (Medscape).
Besides, with an increasing age, the likelihood of being diagnosed with bladder cancer increases (Cancer.Net).
Signs and symptoms
As with any other cancer, bladder cancer too, is painless in the beginning. It presents itself with hematuria which is seen in maximum (80 to 90%) patients. Some patients may also have irritative symptoms like dysuria, and frequent and urgent urination. Sometimes, these symptoms may be present, but the diagnosis may show another medical condition instead of cancer. There are no symptoms as such which will specifically indicate that the illness is bladder cancer (Cancer.Net). In advanced disease, patient may present with pelvic pain, lower extremity edema due to iliac vessel compression, or flank pain (Medscape). There may also be anorexia and unexplained weight loss (Cancer.Net).
Diagnostic methods (physical exam, lab values, imaging modalities)
A bladder cancer patient usually presents with hematuria, which may be continuous or intermittent. Patient may have irritative voiding symptoms. A physical examination is often unremarkable. A bimanual examination may help with clinical staging of the cancer when done at the time of transurethral resection (The management of Bladder Cancer).
A complete blood check (CBC) may be indicative of anemia or an elevated WBC count. Renal function testing to see if kidneys are functioning normally is done by serum creatinine measurements. Urinalysis (urine tests) is done to evaluate the presence of RBCs, WBCs, and proteins. It can also indicate if tumor cells are present (Cancer.Net).
Since microscopic hematuria due to bladder cancer may sometimes be intermittent, even if urinalysis is repeated to give a negative result every time, it does not exclude the diagnosis of bladder cancer. Voided urine cytology is considered to be a standard non-invasive method to assess morphologic changes of the bladder cells. If urine cytology is suggestive of a cancerous growth, then a biopsy needs to be performed. Endoscopic biopsies establish the diagnosis and determine the extent of cancer. However, cytology is still considered to be the most reliable urine test. If positive, it should be treated as an indication of cancer (The management of Bladder Cancer).
Another test – cystoscopy – though expensive, time-consuming, and invasive test, it is now considered to be the gold standard in the evaluation of the disease. This technique helps to directly visualize the lower urinary tract structures and associated pathology. In recent times, ultrasonography seems to be a cost effective and well accepted diagnostic procedure, but it has certain limitations (Stamatiou, 2009).
Ultrasound Appearance
Renal USG is also commonly done, but limited to detect renal masses, bladder intraluminal masses, and hydronephrosis. The 2011 EAU guidelines state that renal USG cannot be used to detect tumors in the upper urinary tract (Emedicine).
The drawbacks with using USG for diagnosis of bladder CA are smaller lesions ( < 0.5cm) as well as lesions located in the neck or the dome of bladder seem to be difficult to visualize on USG. Also, certain external factors like obesity of the patient or degree of bladder distension may lead to misdiagnosis of the cancer (Stamatiou, 2009).
Differential Diagnosis
Since hematuria is the classic presentation, it may resemble a urinary tract infection. Urinary tract infections also cause symptoms like dysuria, and frequent and urgent urination. Carcinoma-in-situ (CIS) may often be misdiagnosed as bladder infection. Some other differential diagnoses in cases of bladder cancer are nephrolithiasis, non-infectious hemorrhagic cystitis, and ureteral trauma (Emedicine).
Treatment
For approach considerations in treatment of cancer, the cancer needs to be differentiated as muscle invasive or non-muscle invasive. Within each category, treatments can be medical or surgical. Patients who have a low grade, low stage tumor may benefit from intravesical chemotherapy. A single instillation is usually enough, but it should be immediate (Emedicine).
For intermediate risk patients and those with recurrence, Bacillus Calmette-Guérin (BCG) immunotherapy or other intravesical chemotherapies can be used. Due to a poor prognosis and substantial risk of recurrence, patients with CIS should be advised to undergo intravesical BCG immunotherapy (Emedicine).
Below table mentions the current treatment alternatives with indications for each of these treatment options (The management of Bladder Cancer):
Intravesical immunotherapy agents are BCG and interferons, whereas chemotherapeutic agents are Mitomycin C, Thiotepa, Doxorubicin, epirubicin, valrubicin, and gemcitabine (The management of Bladder Cancer).
Vigilant surveillance is required due to local recurrence and potential for stage progression. The cancer also necessitates lifelong follow-up (The management of Bladder Cancer).
Prognosis
The recurrence rate is high with 80 % of patients having recurrence at least once; however, the non-invasive bladder cancer has a good prognosis with almost 82 to 100% five- year survival rate. Risk factors for recurrence are female sex, larger size of the tumor mass, multiple tumors, diagnosis and treatment in advanced stage, and presence of CIS. Invasive bladder cancers have a poor prognosis. Factors that predict survival after a recurrence are location of the tumor after recurrence, the patient’s age at the time of diagnosis of recurrent tumor, and treatment given for recurrence (Emedicine).
Social impact of the disease
As with any other cancer, bladder cancer diagnosis too is perceived to be a traumatic event, both to the patient as well as his family and friends. It has a significant impact on patient’s social, emotional, physical, and functional adjustment. Patients have the right to know how different treatment options will influence their quality of life in short and long term; and physicians need to keep all the communication clear to the patient with respect to treatment and its side effects. The affected patient usually needs to change his goals in life and disengage himself from some of the commitments in order to cope with the social and psychological implications (Mohamed, 2012).
References:
Bladder Cancer. Cancer.Net. Available at: http://www.cancer.net/cancer-types/bladder-cancer
Bladder Cancer. Medscape. Available at: http://emedicine.medscape.com/article/438262-overview#aw2aab6b2b4aa
Chapter 1: The Management of Bladder Cancer: Diagnosis and Treatment Recommendations. (2007) American Urological Association Education and Research. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/bladcan07/chapter1.pdf
Stamatiou, K., Papadoliopoulos, I., Dahanis, S., Zafiropoulos, G., Polizois, K. (2009) The accuracy of ultrasonography in the diagnosis of superficial bladder tumors in patients presenting with hematuria. Annals of Saudi Medicine. 29, 134-137. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813642/?report=printable
Mohamed, NE., Diefenbach, MA., Goltz, HH., et al. (2012) Muscle Invasive Bladder Cancer: From Diagnosis to Survivorship. Advances in Urology, Article ID 142153 Available at: http://www.hindawi.com/journals/au/2012/142135/cta/
