With more than 380,000 new cases and 150,000 deaths occurring every year in the world, bladder neoplasm is ranked among the most common malignancies in medical practice [1]. It was considered as the fourth most common cause of cancer in males [1]. But in 2016, data from the United States indicates that its incidence has risen to third place amongst malignant diseases in males (after prostate and lung cancer), with more than 75,000 new cases, of which almost 60,000 are in males [2]. Apart from male gender, cigarette smoking, known as the single most important risk factor for bladder neoplasm, as well as occupational exposure to aromatic amines (frequently in rubber and cable manufacturing) are well-established risk factors [3]. The main clinical presentation is gross painless hematuria, seen in almost 85% of patients when the diagnosis is made [4] [5]. The second important feature of bladder neoplasm is the appearance of asymptomatic microscopic hematuria [4]. In addition, lower urinary tract symptoms (LUTS), such as dysuria, frequent urination, nocturia, etc., have been strongly associated with the development of bladder neoplasms [3], and their unexplained occurrence must be evaluated thoroughly [4]. Unfortunately, their poor follow-up and misdiagnosis as infections or kidney stones are the main factors for a delayed diagnosis [5], and pelvic pain or a palpable pelvic mass, are signs of metastatic dissemination. A very important feature of bladder neoplasms is their recurrence after excision, often at sites rather than at the primary site of the lesion, making long-term monitoring of operated patients mandatory [6].

• Pathologist

  In 1998, the World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) established a new classification system for urothelial neoplasms. [ncbi.nlm.nih.gov]

  A workshop sponsored by the WHO consisting of pathologists, urologists, cytologists, oncologists and basic scientists interested in bladder tumours addressed this subject, and after a follow- -up meeting sponsored by the International Society of Urological [springer.com]

  After the tumor is removed, the pathologist looks at the tumor under the microscope. Depending on the results from the pathologist, further treatment may be needed. [urology.wustl.edu]

  Update for the practicing pathologist: the International Consultation on Urologic Disease — European Association of Urology consultation on bladder cancer. Mod. Pathol. 28, 612–630 (2015). [nature.com]

  Then a pathologist examines the sediment under a microscope. The idea is to detect malformed cancerous cells that may pass into the urine from a cancer. [medicinenet.com]

• Fever

  Medicines may also be given to treat fever or pain. Urinary tract stones (also called nephrolithiasis or urinary calculi) are made up of hard deposits of minerals (mostly calcium) that start forming in the kidney. [cancer.ca]

  Contact the hospital if you have pain or bleeding which becomes worse or lasts longer than two days or if you have signs of infection such as a fever or needing to pass urine more often. [cancerresearchuk.org]

  If you have a high fever after BCG treatment and/or persistent fevers, you should notify your physician. What Types of Surgery Treat Bladder Cancer? Surgery is by far the most widely used treatment for bladder cancer. [emedicinehealth.com]

  They include fever, fatigue, and a burning sensation in the bladder. Interferon is another biological therapy option. [medicalnewstoday.com]

  […] parts of the Middle East and Africa (for example, Egypt), this is the predominant form of bladder cancer and is associated with chronic infection caused by Schistosoma worm (a blood fluke, that causes schistosomiasis, also termed bilharzia or snail fever [medicinenet.com]

• Surgical Procedure

  Surgery Overview Transurethral resection (TUR) of the bladder is a surgical procedure that is used both to diagnose bladder cancer and to remove cancerous tissue from the bladder. [northshore.org]

  New long-term data from a large patient cohort confirm previous findings that emphasize the benefits of limiting the number of surgical procedures requiring anaesthesia and hospitalization in these, often elderly, patients. [nature.com]

  Partial cystectomy — A surgical procedure where the cancerous tissue is removed by cutting out a small piece of the bladder. [medical-dictionary.thefreedictionary.com]

  This procedure, known as radical cystectomy, is a major operation; the doctor and patient should have a thorough discussion about the risks, complications, and benefits prior to this surgical procedure. [medicinenet.com]

  There are a variety of different surgical procedures that can be performed. Some people wear a bag outside the body to collect urine, called noncontinent urinary diversion. [emedicinehealth.com]

• Weight Loss

  A persistent urge to urinate (urinary urgency) Frequent urination (urinary frequency) Back or abdominal pain Loss of appetite Unexplained weight loss Causes Like any cancer, bladder cancer is due to mutated cells that proliferate and form a tumor—in this [verywell.com]

  In the later stages, there may be back pain, weight loss, swelling in the feet, bone pain, and an inability to urinate. Symptoms of bladder cancer can resemble those of a less severe problem such as a bladder infection. [medicalnewstoday.com]

  And in the uncommon cases of widespread disease, the first symptoms of bladder cancer can be belly, back, or bone pain, or weight loss. [health.harvard.edu]

  People who took this herb as part of a weight loss program had higher rates of bladder cancer and kidney failure than the general population. Scientific studies on this herb have shown that it contains chemicals that can cause cancer in rats. [emedicinehealth.com]

• Chronic Infection

  […] the presence of gross hematuria in most cases.  The most frequent presenting symptom is gross hematuria, often in conjunction with a urinary tract infection.  Transurethral resection and elimination of the chronic irritation. 11. [slideshare.net]

  View/Print Table Table 1 Risk Factors for Bladder Cancer Behavioral Cigarette smoking Chemical exposure Arsenic in well water Chronic infection Bladder calculi, chronic bladder infection, genitourinary tuberculosis, long-term indwelling catheter, schistosomiasis [aafp.org]

  Long-term chronic infections of the bladder, irritation due to stones or foreign bodies, and infections with the blood fluke prevalent in certain regions of the world (as mentioned earlier) are some other factors that predispose to bladder cancer. [medicinenet.com]

• Dyspnea

  […] of incomplete voiding, intermittent stream, straining Signs and symptoms of metastases or advanced disease Abdominal, bone, flank, or pelvic pain; anorexia, cachexia, or pallor; lower extremity edema; renal failure; respiratory symptoms (e.g., cough, dyspnea [aafp.org]

  The most common adverse events were elevated lipase or amylase, fatigue, rash, dyspnea, lymphopenia, and neutropenia. [cancer.gov]

• Hematuria

  The main clinical presentation is gross painless hematuria, seen in almost 85% of patients when the diagnosis is made. The second important feature of bladder neoplasm is the appearance of asymptomatic microscopic hematuria. [symptoma.com]

  Herein, we reported a 59-year-old female patient consulted to our outpatient clinic with the incidents of hematuria. [ncbi.nlm.nih.gov]

  Hematuria was not noted on postoperative urinalysis. Discussion Gross hematuria in children is a relatively uncommon manifestation, accounting for about 1 in 1,000 outpatient visits. [e-ultrasonography.org]

• Incontinence

  Some common ones are Cystitis - inflammation of the bladder, often from an infection Urinary incontinence - loss of bladder control Overactive bladder - a condition in which the bladder squeezes urine out at the wrong time Interstitial cystitis - a chronic [icdlist.com]

  Instruct the patient on methods for performing Kegel exercises during and between voidings to minimize incontinence. Suggest wearing incontinence pads until full control is achieved. [medical-dictionary.thefreedictionary.com]

  View/Print Table Table 4 Signs and Symptoms of Bladder Cancer Hematuria (gross or microscopic) Irritative symptoms Dysuria, frequency, urge incontinence, urgency Obstructive symptoms Decreased force of stream, feeling of incomplete voiding, intermittent [aafp.org]

  This procedure is also termed incontinent diversion. [medicinenet.com]

  Prognosis Untreated bladder cancer produces significant morbidity, including the following: Hematuria Dysuria Irritative urinary symptoms Urinary retention Urinary incontinence Ureteral obstruction Pelvic pain The recurrence rate for superficial TCC of [emedicine.medscape.com]

• Nocturia

  In addition, lower urinary tract symptoms (LUTS), such as dysuria, frequent urination, nocturia, etc., have been strongly associated with the development of bladder neoplasms, and their unexplained occurrence must be evaluated thoroughly. [symptoma.com]

  Other symptoms may include suprapubic pain after voiding, bladder irritability, dribbling, and nocturia. Physical examination The physical examination is usually normal. [medical-dictionary.thefreedictionary.com]

  Less commonly, patients may complain of urinary frequency, nocturia, and dysuria, symptoms that are more common in patients with carcinoma in situ. [cancer.gov]

• Urinary Incontinence

  Some common ones are Cystitis - inflammation of the bladder, often from an infection Urinary incontinence - loss of bladder control Overactive bladder - a condition in which the bladder squeezes urine out at the wrong time Interstitial cystitis - a chronic [icdlist.com]

  […] continence; Urinary elimination; Knowledge: Disease process and treatment regime; Self-care: Toileting; Self-esteem Interventions Urinary elimination management; Urinary incontinence care; Teaching: Individual; Fluid monitoring; Urinary catheterization [medical-dictionary.thefreedictionary.com]

  Prognosis Untreated bladder cancer produces significant morbidity, including the following: Hematuria Dysuria Irritative urinary symptoms Urinary retention Urinary incontinence Ureteral obstruction Pelvic pain The recurrence rate for superficial TCC of [emedicine.medscape.com]

• Urinary Retention

  […] catheters (Medical Encyclopedia) Urinary Retention - NIH (National Institute of Diabetes and Digestive and Kidney Diseases) [ Read More ] [icdlist.com]

  Additionally, a tumor near the urethral orifice may result in bladder outlet obstruction and urinary retention. Occasionally patients only present once systemic symptoms of a metastatic disease are present. [radiopaedia.org]

  Prognosis Untreated bladder cancer produces significant morbidity, including the following: Hematuria Dysuria Irritative urinary symptoms Urinary retention Urinary incontinence Ureteral obstruction Pelvic pain The recurrence rate for superficial TCC of [emedicine.medscape.com]

Signs and symptoms of bladder neoplasm may be insidious and are often absent in its early stages, making the diagnosis difficult. In the setting of macroscopic hematuria, however, bladder cancer must be excluded as the underlying cause. A detailed patient history regarding the onset of symptoms and their progression is the first step, followed by a thorough physical examination of the abdomen and a prostate exam, as prostate cancer must be excluded as well. Urinalysis is also a valuable diagnostic procedure that can reveal microscopic hematuria, which is particularly valuable in the absence of other symptoms [5]. Urine cytology is also an important diagnostic method used to detect the presence of malignant cells that have been shed from the tumor into urine [5]. However, cystoscopy is considered to be the gold standard, although it is invasive and highly unpleasant [1] [5]. Cystoscopy provides a viable sample for biopsy and enables adequate classification according to TNM staging [7]:

• Tumor (T) - Depending on the depth of tissue infiltration, tumors are divided into the following stages: Noninvasive papillary lesions (Ta), carcinoma in situ (Tis), lesions that invade the subepithelial connective tissue (T1), muscle (either superficial or deep, demarcated as T2a and T2b, respectively), perivesicular tissue, either microscopic or macroscopic (T3a and T3b), and tumors that invade adjacent organs (infiltration of the prostate, uterus, or vagina are designated as T4a, whereas T4b denotes invasion of the pelvic or abdominal wall).
• Nodal involvement (N) - Infiltration of adjacent lymph nodes by the tumor is not seen in the initial stages of the disease (N0), but further development results in infiltration of only one node in the pelvis (N1), 2 or more in the same area (N2) or 1 or more iliac nodes (N3).
• Metastasis (M) - Presence of metastases (M1) confirms the advanced stage of the disease and carries a very poor prognosis.

In order to define the tumor stage, histopathological findings must be supported by imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI). However, the diagnosis primarily relies on the extent of the primary tumor and its spread such as nodal and metastatic involvement indicating advanced (IV) disease [7]. Recent studies have evaluated several markers that may be of use in the diagnostic workup such as apolipoprotein E (APOE), fibrinogen β chain precursor (FGB) and polymerase (RNA) I polypeptide E (POLR1E) which have shown promising results [1].

Treatment - Bladder neoplasm The treatment of bladder neoplasm depends on how deep the tumor invades into the bladder wall. [checkorphan.org]

Treatment Treatment for bladder cancer depends on the stage of the tumor. The patient's medical history, overall health status, and personal preferences also are taken into account when deciding on an appropriate treatment plan. [medical-dictionary.thefreedictionary.com]

Treatment The treatment of bladder cancer varies by the stage of the disease and whether other organs have been affected. Ta, Tis, and T1 tumors The mainstay of treatment of Ta, Tis, and T1 cancers is the surgical removal of visible tumors. [verywell.com]

These factors have led to braoder programs of combined integrated multimodal treatment earlier in the course of the disease process. [books.google.com]

The most striking features of this case included the histopathologic findings and rapid disease progression, despite treatment with agents known for their efficacy against tumors of epithelial and mesenchymal origin. [ncbi.nlm.nih.gov]

Prognosis  Non–muscle invasive bladder cancer has a good prognosis, with 5-year survival rates of 82-100%. [slideshare.net]

Bladder tumors rarely occur in the first two decades of life, and, in contrast to the cases in adults, 97% of transitional cell carcinomas of the bladder in childhood are low grade, superficial, and of good prognosis, with a progression rate of only 2% [ncbi.nlm.nih.gov]

Metastasis (M) - Presence of metastases (M1) confirms the advanced stage of the disease and carries a very poor prognosis. [symptoma.com]

Xanthogranulomatous cystitis is a rare, benign chronic inflammatory disorder with unclear etiology. Since its similar features to bladder neoplasm, it is extremely easy to be mistaken for malignant tumor. [ncbi.nlm.nih.gov]

Cancer of bladder 1) Incidence and prevalence. 2) Etiology/ Risk factors. 3) Pathology. 4) Clinical features. 5) Investigation and diagnosis. 6) Staging and Management. 7) Prognosis 18. [slideshare.net]

Even after 5 years, however, patients continue to fail not only locally and regionally but also with disseminated disease, thereby creating enigmas as to the continued influence of basic molecular changes, basic etiologic agents, and unsuspected more [books.google.com]

Neoplasms of the bladder account for a very small proportion of known etiologies. [e-ultrasonography.org]

The etiology in these cases is thought to be multifactorial, potentially involving exposure to numerous carcinogens. Arsenic exposure may be a factor in the development of bladder cancer. [emedicine.medscape.com]

[…] urothelial papilloma but with increased cellular proliferation exceeding the thickness of normal urothelium; appears to lack the capacity to invade or metastasize ICD-O: 8130 / 1 Terminology PUNLUMP: papillary urothelial neoplasm of low malignant potential Epidemiology [pathologyoutlines.com]

Bladder cancer: Epidemiology, staging and grading and diagnosis. Urology, 66: 4-34. Direct Link | Kundra, V. and P.M. Silverman, 2003. Imaging in the diagnosis, staging, and Follow-up of cancer of the urinary bladder. Am. J. [scialert.net]

[…] transitional cell carcinoma of the urinary tract TCCs in other locations: transitional cell carcinoma of the renal pelvis transitional cell carcinoma of the ureter other histologies: squamous cell carcinoma of the bladder adenocarcinoma of the bladder Epidemiology [radiopaedia.org]

C 19, 20 Epidemiology Bladder cancer is the fourth most common cancer in men and the eighth most common in women. [aafp.org]

Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009 Sep. 56(3):430-42. [Medline]. [emedicine.medscape.com]

Nonurothelial primary bladder tumors are extremely rare and may include small cell carcinoma, carcinosarcoma, primary lymphoma, and sarcoma (see Pathophysiology ). [emedicine.medscape.com]

It helps to prevent the tumor from coming back and helps prevent development of muscle invasive disease. About 6 weeks after completing the BCG, the doctor will do a cystoscopy again to make sure all of the cancer is gone. [urology.wustl.edu]

Preventing bladder cancer While it is not possible to prevent bladder cancer, it is possible to reduce your risks such as not smoking or quitting smoking, and avoiding exposure to chemicals listed above. [cancer.org.au]

Prevention Since the exact causes of bladder cancer are not known, there is no certain way to prevent it. Avoiding risk factors whenever possible is the best alternative. [medical-dictionary.thefreedictionary.com]

Immunotherapy by intravesicular delivery of Bacillus Calmette–Guérin (BCG) is also used to treat and prevent the recurrence of superficial tumors. [checkorphan.org]

What To Expect Following surgery, a catheter may be placed in the urethra to help stop bleeding and to prevent blockage of the urethra. When the bleeding has stopped, the catheter is removed. You may need to stay in the hospital 1 to 4 days. [northshore.org]

1. Lindén M, Segersten U, Runeson M, Wester K, Busch C, Pettersson U, et al. Tumour expression of bladder cancer-associated urinary proteins. BJU Int. 2013;112(3):407-415.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.
3. Zhou J, Kelsey KT, Smith S, Giovannucci E, Michaud DS. Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results from the Health Professionals Follow-Up Study. Urology. 2015;85(6):1312-1318.
4. Dobbs RW, Hugar LA, Revenig LM, Al-Qassab S, Petros JA, Ritenour CW, et al. Incidence and clinical characteristics of lower urinary tract symptoms as a presenting symptom for patients with newly diagnosed bladder cancer. Int Braz J Urol. 2014;40(2):198-203.
5. Garg T, Pinheiro LC, Atoria CL, et al. Gender Disparities in Hematuria Evaluation and Bladder Cancer Diagnosis: A Population-Based Analysis. J Urol. 2014;192(4):1072-1077.
6. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
7. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.