Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Bladder Cancer

  • Author: Gary David Steinberg, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Jun 02, 2016
 

Practice Essentials

Bladder cancer is a common urologic cancer that has the highest recurrence rate of any malignancy. In North America, South America, Europe, and Asia, the most common type is transitional cell carcinoma. Other types include squamous cell carcinoma (see the image below) and adenocarcinomas.

Cross-section through the bladder, uterus, and vag Cross-section through the bladder, uterus, and vagina with squamous cell carcinoma of the bladder infiltrating through the bladder wall into the vaginal wall.

Signs and symptoms

Clinical manifestations of bladder cancer are as follows:

  • Painless gross hematuria - Approximately 80-90% of patients; classic presentation
  • Irritative bladder symptoms (eg, dysuria, urgency, frequency of urination) - 20-30% of patients
  • Pelvic or bony pain, lower-extremity edema, or flank pain - In patients with advanced disease
  • Palpable mass on physical examination - Rare in superficial bladder cancer

See Clinical Presentation for more detail.

Diagnosis

Urine studies include the following:

  • Urinalysis with microscopy
  • Urine culture to rule out infection, if suspected
  • Voided urinary cytology
  • Urinary tumor marker testing

Urinary cytology

  • Standard noninvasive diagnostic method
  • Low sensitivity for low-grade and early stage cancers
  • Fluorescence in situ hybridization (FISH) may improve the accuracy of cytology

Cystoscopy

  • The primary modality for the diagnosis of bladder carcinoma
  • Permits biopsy and resection of papillary tumors

Upper urinary tract imaging

  • Necessary for the hematuria workup
  • American Urologic Association Best Practice Policy recommends computed tomography (CT) scanning of the abdomen and pelvis with contrast, with preinfusion and postinfusion phases
  • Imaging is ideally performed with CT urography, using multidetector CT
  • Ultrasonography is commonly used, but it may miss urothelial tumors of the upper tract and small stones

The diagnostic strategy for patients with negative cystoscopy is as follows:

  • Negative urine cytology and FISH - Routine follow-up
  • Negative urine cytology, positive FISH - Increased frequency of surveillance
  • Positive urine cytology, positive or negative FISH - Cancer until proven otherwise

No blood tests are specific for bladder cancer, but a general evaluation is necessary prior to initiating therapy with intravesical bacillus Calmette-Guérin (BCG) vaccine. Laboratory tests include the following:

  • Complete blood count (CBC)
  • Liver function tests
  • Bony fraction of alkaline phosphatase assay (if bone metastasis suspected)
  • Kidney function studies

See Workup for more detail.

Management

The treatment of non–muscle-invasive bladder cancer (Ta, T1, carcinoma in situ [CIS]) begins with transurethral resection of bladder tumor (TURBT). Subsequent treatment is as follows:

  • Small-volume, low-grade Ta bladder cancer - An immediate single, postoperative dose of intravesical chemotherapy
  • High-risk Ta, T1, and CIS urothelial carcinoma - Intravesical BCG vaccine
  • Persistent or recurrent high-risk disease - Repeat resection prior to additional intravesical therapy (eg, interferon alfa or gamma); consider cystectomy for high-risk disease

The treatment of muscle-invasive bladder cancer is as follows:

  • Radical cystoprostatectomy in men
  • Anterior pelvic exenteration in women
  • Bilateral pelvic lymphadenectomy (PLND), standard or extended
  • Creation of a urinary diversion
  • Neoadjuvant chemotherapy - May improve cancer-specific survival

Alternatively, a bladder-sparing approach of TURBT followed by concurrent radiation therapy and systemic chemotherapy (trimodality therapy) may be used.

Chemotherapeutic regimens for metastatic bladder cancer include the following:

  • Methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC)
  • Gemcitabine and cisplatin (GC)

See Treatment and Medication for more detail.

Next

Background

Bladder cancer is a common urologic cancer. Almost all bladder cancers originate in the urothelium, which is a 3- to 7-cell mucosal layer within the muscular bladder.

Transitional (urothelial) cell carcinoma

In North America, South America, Europe, and Asia, the most common type of urothelial tumor diagnosed is transitional (urothelial) cell carcinoma (TCC); it constitutes more than 90% of bladder cancers in those regions. TCC can arise anywhere in the urinary tract, including the renal pelvis, ureter, bladder, and urethra, but it is usually found in the urinary bladder. Carcinoma in situ (CIS) is frequently found in association with high-grade or extensive TCC. (See the image below.)

The classic appearance of carcinoma in situ as a f The classic appearance of carcinoma in situ as a flat, velvety patch. However, using special staining techniques such as 5-aminolevulinic acid, it has been shown that significant areas of carcinoma in situ are easily overlooked by conventional cystoscopy. Courtesy of Abbott and Vysis Inc.

Squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common cell type associated with bladder cancer in industrialized countries. In the United States, around 5% of bladder cancers are SCCs.[1] Worldwide, however, SCC is the most common form of bladder cancer, accounting for 75% of cases in developing nations (see Epidemiology).

In the United States, the development of SCC is associated with persistent inflammation from long-term indwelling Foley catheters and bladder stones, as well as, possibly, infections. In developing nations, SCC is often associated with bladder infection by Schistosoma haematobium (see Etiology).

Other types of bladder cancer

Approximately 2% of bladder cancers are adenocarcinomas. Nonurothelial primary bladder tumors are extremely rare and may include small cell carcinoma, carcinosarcoma, primary lymphoma, and sarcoma (see Pathophysiology). Small cell carcinoma of the urinary bladder accounts for only 0.3-0.7% of all bladder tumors. High-grade urothelial carcinomas can also show divergent histologic differentiation, such as squamous, glandular, neuroendocrine, and sarcomatous features.

Phenotypes

Clinical and pathologic data indicate that at least 3 different phenotypes, as follows, exist in urothelial carcinoma[2, 3] :

  • Low-grade proliferative lesions that develop into non–muscle-invasive tumors; these account for approximately 80% of bladder cancers
  • Highly proliferative invasive tumors with a propensity to metastasize
  • CIS, which can penetrate the lamina propria and eventually progress

Clinical course

The clinical course of bladder cancer is marked by a broad spectrum of aggressiveness and risk. Low-grade, superficial bladder cancers have minimal risk of progression to death; however, high-grade non–muscle-invasive cancers frequently progress and muscle-invasive cancers are often lethal (see Prognosis).

The classic presentation of bladder cancer is painless gross hematuria, which is seen in approximately 80-90% of patients. Physical examination results are often unremarkable (see Presentation). Cystoscopy, cytology, and biopsy when necessary are the principal diagnostic tests (see Workup).

Upon presentation, 55-60% of patients have low-grade, noninvasive disease, which is usually treated conservatively with transurethral resection of bladder tumor (TURBT) and periodic cystoscopy. Intravesical agents may also be given selectively to decrease the frequency of recurrences. The remaining patients have high-grade disease, of which 50% is muscle invasive and is typically treated with radical cystectomy or with trimodality therapy (ie, TURBT followed by concurrent radiation therapy and systemic chemotherapy; see Treatment).

Carcinoma in situ (CIS) is managed by TURBT and instillation of chemotherapeutic or immunotherapeutic agents—most commonly, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine—into the bladder via catheter. These intravesical treatments are not effective in the 20% of patients in whom cancer has invaded the bladder wall muscle; those cases require cystectomy or a combination of radiation therapy and chemotherapy (see Treatment).

Bladder cancer has the highest recurrence rate of any malignancy. Although most patients with bladder cancer can be treated with organ-sparing therapy, most experience either recurrence or progression, creating a great need for accurate and diligent surveillance (see Treatment).

For more information on bladder cancer, see the following:

Previous
Next

Anatomy

The bladder is an extraperitoneal muscular urine reservoir that lies behind the pubis symphysis in the pelvis. At the dome of the bladder lies the median umbilical ligament, a fibrous cord that is anchored to the umbilicus and that represents the obliterated urachus (allantois). The ureters, which transport urine from kidney to bladder, approach the bladder obliquely and posterosuperiorly, entering at the trigone (the area between the interureteric ridge and the bladder neck). The intravesical ureteral orifices are roughly 2-3 cm apart and form the superolateral borders of the trigone. The bladder neck serves as an internal sphincter, which is sacrificed during a radical cystectomy.

In males, the seminal vesicles, vas deferens, ureters, and rectum border the inferoposterior aspect of the bladder. Anterior to the bladder is the space of Retzius, which is composed of fibroadipose tissue and the prevesical fascia. The dome and posterior surface of the bladder are covered by parietal peritoneum, which reflects superiorly to the seminal vesicles and is continuous with the anterior rectal peritoneum. In females, the posterior peritoneal reflection is continuous with the uterus and vagina.

The vascular supply to the bladder arrives primarily via the internal iliac (hypogastric) arteries, branching into the superior, middle, and inferior vesical arteries, which are often recognizable as lateral and posterior pedicles. The arterial supply also arrives via the obturator and inferior gluteal artery and, in females, via the uterine and vaginal arteries. Bladder venous drainage is a rich network that often parallels the named arterial vessels, most of which ultimately drain into the internal iliac vein.

Initial lymphatic drainage from the bladder is primarily into the external iliac, obturator, internal iliac (hypogastric), and common iliac nodes. Following the drainage to these sentinel pelvic regions, spread may continue to the presacral, paracaval, interaortocaval, and para-aortic lymph node chains.

Almost all bladder cancers originate in the urothelium, which is a 3- to 7-cell mucosal layer within the muscular bladder. Squamous cell carcinoma of the bladder can involve multiple sites; however, the lateral wall and trigone are more commonly involved by this tumor. All small cell carcinomas of the urinary system identified so far have been located in the urinary bladder, most commonly in the dome and vesical lateral wall.[4]

See Bladder Anatomy.

Previous
Next

Pathophysiology

Bladder cancer is often described as a polyclonal field change defect with frequent recurrences due to a heightened potential for malignant transformation. However, bladder cancer has also been described as resulting from implantation of malignant cells that have migrated from a previously affected site. The latter occurs less often and may account for only a small percentage of cases.

Use of the common term superficial bladder cancer should be discouraged. The term implies a harmless nature, which is misleading in many instances. Because it was used to describe the disparate disorders of low-grade papillary bladder cancer and the markedly more aggressive form, carcinoma in situ (CIS), the World Health Organization (WHO) has recommended it be abandoned.

In its place, the term non–muscle-invasive bladder cancer should be used and qualified with the appropriate American Joint Committee on Cancer stage (ie, Ta, T1, Tis). Stage T1 cancer invades lamina propria but not the muscle of the bladder. High-grade T1 tumor associated with CIS carries a relatively high risk for disease recurrence and progression (approximately 60%).

The WHO classifies bladder cancers as low grade (grades 1 and 2) or high grade (grade 3). Tumors are also classified by growth patterns: papillary (70%), sessile or mixed (20%), and nodular (10%). (See the images below.)

Papillary bladder tumors such as this one are typi Papillary bladder tumors such as this one are typically of low stage and grade (Ta-G1). Courtesy of Abbott and Vysis Inc.
Sessile lesions as shown usually invade muscle, al Sessile lesions as shown usually invade muscle, although occasionally a tumor is detected at the T1-G3 stage prior to muscle invasion. Courtesy of Abbott and Vysis Inc.

Transitional cell carcinoma

Transitional cell carcinoma (TCC) arises from stem cells that are adjacent to the basement membrane of the epithelial surface. Depending on the genetic alterations that occur, these cells may follow different pathways in the expression of their phenotype.

The most common molecular biologic pathway for TCCs involves the development of a papillary tumor that projects into the bladder lumen and, if untreated, eventually penetrates the basement membrane, invades the lamina propria, and then continues into the bladder muscle, where it can metastasize. Nearly 90% of transitional cell bladder tumors exhibit this type of behavior.

This progression occurs with high-grade cancers only. Low-grade cancers rarely, if ever, progress and are thought to have a distinct molecular pathway, different from the high-grade cancers and CIS.

The remaining 10% of TCCs follow a different molecular pathway and are called CIS. This is a flat, noninvasive, high-grade urothelial carcinoma tumor that spreads along the surface of the bladder and, over time, may progress to an invasive form of cancer that behaves the same as invasive TCC.

Many urothelial tumors are primarily composed of TCC but contain small areas of squamous differentiation, squamous cell carcinoma (SCC), or adenocarcinoma.

Squamous cell carcinoma

SCC of the urinary bladder is a malignant neoplasm that is derived from bladder urothelium and has a pure squamous phenotype.[5, 6, 7] SCC of the bladder is essentially similar to squamous cell tumors arising in other organs. Because many urothelial carcinomas contain a minor squamous cell component, a diagnosis of SCC of the bladder should be rendered only when the tumor is solely composed of squamous cell components, with no conventional urothelial carcinoma component.

Reportedly, SCC has less of a tendency for nodal and vascular distant metastases than does urothelial carcinoma.[8, 9]

Rare forms of bladder cancer

Adenocarcinomas account for less than 2% of primary bladder tumors. These lesions are observed most commonly in exstrophic bladders and are often associated with malignant degeneration of a persistent urachal remnant.

Other rare forms of bladder cancer include leiomyosarcoma, rhabdosarcoma, carcinosarcoma, lymphoma, and small cell carcinoma. Leiomyosarcoma is the most common sarcoma of the bladder. Rhabdomyosarcomas most commonly occur in children. Carcinosarcomas are highly malignant tumors that contain a combination of mesenchymal and epithelial elements. Primary bladder lymphomas arise in the submucosa of the bladder. Except for lymphomas, all these rare bladder cancers carry a poor prognosis.

Small cell carcinoma of the urinary bladder is a poorly differentiated, malignant neoplasm that originates from urothelial stem cells and has variable expression of neuroendocrine markers. Morphologically, it shares features of small cell carcinoma of other organs, including the lung.

Genetic factors in pathogenesis

Divergent, yet interconnected and overlapping, molecular pathways are likely responsible for the development of noninvasive and invasive bladder tumors. Somatic mutations in fibroblast growth receptor3 (FGFR-3) and tumor protein p53 (TP53) in tumor cells appear to be important early molecular events in the noninvasive and invasive pathways, respectively.

FGFR-3, Ras, and PIK3CA mutations occur with high frequency in noninvasive tumors, leading to upregulation of Akt and mitogen-activated protein kinase (MAPK).[10, 11] Loss of heterozygosity (LOH) on chromosome 9 is among the most frequent genetic alterations in bladder tumors and is considered an early event.[12]

Large numbers of genomic changes have been detected using karyotyping and comparative genomic hybridization (CGH) analysis in urothelial carcinoma. Numerically common are losses of 2q, 5q, 8p, 9p, 10q, 18q, and Y. Gains of 1q, 5p, 8q, and 17q are frequently present, and high-level amplifications can be found; however, the target genes in the regions of amplifications have not been conclusively identified.[13]

Alterations in the TP53 gene are noted in approximately 60% of invasive bladder cancers. Progression-free survival is significantly shorter in patients with TP53 mutations and is an independent predictor of death among patients with muscle-invasive bladder cancer.[14]

Additionally, alterations in retinoblastoma (Rb), PTEN, and p16 are common in high-grade invasive cancers.[15] Overexpression of JUN, MAP2K6, STAT3, and ICAM1 and molecules associated with survival (Bcl-2, caspase-3, p53, survivin), as well as insensitivity to antigrowth signals (p53, p21, p16, pRB), has been demonstrated.[16]

In advanced disease, multiple mechanisms may lead to tumor progression. These include those that promote proliferation, survival, invasion, and metastasis, as well as those that involve deficiencies in DNA damage repair and the finding of stemlike cells.

In addition to tumor cell alterations, the microenvironment may promote tumor growth by paracrine influences, including vascular endothelial growth factor (VEGF) production and aberrant E-cadherin expression. Finally, a growing body of research over the last decade indicates that epigenetic alterations may silence tumor suppressor genes and that they represent important events in tumor progression.[17, 18, 19]

Previous
Next

Etiology

Up to 80% of bladder cancer cases are associated with environmental exposure. Tobacco use is by far the most common cause of bladder cancer in the United States and is increasing in importance in some developing countries. Smoking duration and intensity are directly related to increased risk.[20, 21, 1]

The risk of developing bladder carcinoma is 2-6 times greater in smokers than in nonsmokers. This risk appears to be similar between men and women.[22] Nitrosamine, 2-naphthylamine, and 4-aminobiphenyl are possible carcinogenic agents found in cigarette smoke.

A number of occupations involve exposure to substances that may increase risk for bladder cancer. Of occupationally related bladder cancer cases, the incidence rate is highest in workers exposed to aromatic amines, while mortality is greatest in those exposed to polycyclic aromatic hydrocarbons and heavy metals.[23]

Numerous occupations associated with diesel exhaust, petroleum products, and solvents (eg, auto work, truck driving, plumbing, leather and apparel work, rubber and metal work) have also been associated with an increased risk of bladder cancer. In addition, increased bladder carcinoma risk has been reported in persons, including the following, who work with organic chemicals and dyes:

  • Beauticians
  • Dry cleaners
  • Painters
  • Paper production workers
  • Rope-and-twine industry workers
  • Dental workers
  • Physicians
  • Barbers

People living in urban areas are also more likely to develop bladder cancer. 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. Results of a population-based case-control study in Maine, New Hampshire, and Vermont support an association between low-to-moderate levels of arsenic in drinking water and bladder cancer risk in those states, where incidence rates of bladder cancer have long been about 20% higher than in the United States overall.[24] A likely source of the arsenic is residue of arsenic-based pesticides, which were used extensively on crops such as blueberries, apples, and potatoes in that region from the 1920s through to the 1950s.[25]

Several medical risk factors are associated with an increased risk of bladder cancer, including the following:

  • Radiation treatment of the pelvis
  • Chemotherapy with cyclophosphamide - Increases the risk of bladder cancer via exposure to acrolein, a urinary metabolite of cyclophosphamide [26]
  • Spinal cord injuries requiring long-term indwelling catheters - A 16- to 20-fold increase in the risk of developing SCC of the bladder

Although certain common genetic polymorphisms appear to increase susceptibility in persons with occupational exposure associated with increased bladder cancer risk,[27] no convincing evidence exists for a hereditary factor in the development of bladder cancer. Nevertheless, familial clusters of bladder cancer have been reported.

Schistosomiasis

In many developing countries, particularly in the Middle East, Schistosoma haematobium infection causes most cases of bladder SCC. In a study from Egypt, 82% of patients with bladder carcinoma harbored S haematobium eggs in the bladder wall. In egg-positive patients, the tumor tended to develop at a younger age (with SCC predominant) than it did in egg-negative persons. A higher degree of adenocarcinoma has also been reported in schistosomal-associated bladder carcinomas.[28]

Along with S haematobium, the species S mansoni and S japonicum are responsible for schistosomiasis in humans. The eggs reside in the pelvic and mesenteric venous plexus. In the bladder, a severe inflammatory response and fibrosis secondary to the deposition of Schistosoma eggs is common. (See the image below.)

Histopathology of bladder shows eggs of Schistosom Histopathology of bladder shows eggs of Schistosoma haematobium surrounded by intense infiltrates of eosinophils and other inflammatory cells.

The eggs are found embedded in the lamina propria and muscularis propria of the bladder wall. Many of the eggs are destroyed by host reaction and become calcified, resulting in a lesion commonly known as a sandy patch, which appears as a granular, yellow-tan surface lesion.

In normal epithelial cells, S haematobium total antigen reportedly induces increased proliferation, migration, and invasion and decreases apoptosis.[29] Keratinous squamous metaplasia has been associated with the increased risk of developing SCC, with approximately one half of the cases arising subsequent to the metaplasia.[30, 31]

The majority of schistosomiasis-related cases of SCC will arise in the setting of chronic cystitis.[32] Chronic irritation secondary to lithiasis,[5, 6] urinary retention, and indwelling catheters has also been linked to the development of SCC.[6]

Other squamous cell carcinoma risk factors

Having bladder diverticula may increase an individual’s chance of developing SCC.[33] Rarely, bacillus Calmette-Guerin (BCG) treatment for CIS has been reported to lead to development of SCC.[34] Development of bladder cancer at a younger age has been associated with bladder exstrophy.[35, 36, 37, 38] SCC has also been described in urachal remnants.[39, 40, 41, 42, 43]

Coffee consumption does not increase the risk of developing bladder cancer. Early studies of rodents and a minority of human studies suggested a weak connection between artificial sweeteners (eg, saccharin, cyclamate) and bladder cancer; however, most recent studies show no significant correlation.

Previous
Next

Epidemiology

Occurrence in the United States

The American Cancer Society estimates that 76,960 new cases of bladder cancer will be diagnosed in the United States in 2016 and that 16,390 people will die of the disease.[44] The incidence of bladder cancer increases with age, with the median age at diagnosis being 65 years; bladder cancer is rarely diagnosed before age 40 years.[45]

Bladder cancer is about 3 times more common in men than in women. Over the past 2 decades, however, the rate of bladder cancer has been stable in men but has increased in women by 0.2% annually.[46] The male predominance in bladder cancer in the United States reflects the prevalence of transitional cell carcinoma (TCC). With SCC—in contrast to TCC—the male-to-female incidence ratio is 1:2.

Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer, but it is not among the top 10 cancers in women. Accordingly, more men than women are expected to die of bladder cancer in 2016, with 11,820 deaths in men versus 4570 in women.[44] Nevertheless, women generally have a worse prognosis than men.

The incidence of bladder cancer is twice as high in white men as in black men in the United States. However, blacks have a worse prognosis than whites.[46, 47]

Limited data indicate that small cell carcinoma of the urinary bladder probably has the same epidemiologic characteristics as urothelial carcinoma. Patients are more likely to be male and older than 50 years.[48, 49]

International occurrence

Worldwide, bladder cancer is diagnosed in approximately 275,000 people each year, and about 108,000 die of this disease. In industrialized countries, 90% of bladder cancers are TCC. In developing countries—particularly in the Middle East and Africa—the majority of bladder cancers are SCCs, and most of these cancers are secondary to Schistosoma haematobium infection. Recent studies report that urothelial carcinoma is the most common urologic cancer in China.

In Africa, the highest incidence of SCC has been seen in schistosomal-endemic areas, notably Sudan and Egypt, where SCC ranges from two thirds to three quarters of all malignant tumors of the bladder. In recent years, a few studies from Egypt have shown a reversal of this trend due to the better control of schistosomiasis in the region, whereas in other parts of Africa the association is unchanged.[9, 50, 51] Increased smoking incidence is believed to have contributed to the shift in Egypt toward TCC, which has a stronger smoking association.

Previous
Next

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 the bladder is high. As many as 80% of patients have at least one recurrence.

The most significant prognostic factors for bladder cancer are grade, depth of invasion, and the presence of CIS. In patients undergoing radical cystectomy for muscle-invasive bladder cancer, the presence of nodal involvement is the most important prognostic factor. To date, there is no convincing evidence of genetic factors affecting outcome.[52]

Non–muscle invasive bladder cancer has a good prognosis, with 5-year survival rates of 82-100%. The 5-year survival rate decreases with increasing stage, as follows:

  • Ta, T1, CIS – 82-100%
  • T2 – 63-83%
  • T3a – 67-71%
  • T3b – 17-57%
  • T4 – 0-22%

Prognosis for patients with metastatic urothelial cancer is poor, with only 5-10% of patients living 2 years after diagnosis.

The risk of progression, defined as an increased tumor grade or stage, depends primarily on the tumor grade, as follows:

  • Grade I – 2-4%
  • Grade II – 5-7%
  • Grade III – 33-64%

Prognosis in carcinoma in situ

CIS in association with T1 papillary tumor carries a poorer prognosis. It has a recurrence rate of 63-92% and a rate of progression to muscle invasion of 50-75% despite intravesical BCG. Diffuse CIS is an especially ominous finding; in one study, 78% of cases progressed to muscle-invasive disease.[53]

Prognosis in squamous cell carcinoma

Tumor stage, lymph node involvement, and tumor grade have been shown to be of independent prognostic value in SCC.[54, 55] However, pathologic stage is the most important prognostic factor. In one relatively large series of 154 cases, the overall 5-year survival rate was 56% for pT1 and 68% for pT2 tumors. However, the 5-year survival rate for pT3 and pT4 tumors was only 19%.[52]

Several studies have demonstrated grading to be a significant morphologic parameter in SCC.[52] In one series, 5-year survival rates for grade 1, 2, and 3 squamous cell carcinoma was 62%, 52%, and 35%, respectively.[52] In the same study of patients undergoing cystectomy, the investigators suggested that a higher number of newly formed blood vessels predicts unfavorable disease outcome.

In SCC, the survival rate appears to be better with radical surgery than with radiation therapy and/or chemotherapy. In locally advanced tumors, however, neoadjuvant radiation improves the outcome.[56] Sex and age have not been prognostically significant in SCC.[52]

Prognosis in small cell carcinoma

Patients with small cell carcinoma of the bladder usually have disease in an advanced stage at diagnosis, and they have a poor prognosis.[57, 58, 59] Overall median survival is only 1.7 years. The 5-year survival rates for stage II, III, and IV disease are 64%, 15%, and 11%, respectively.[60]

Recurrent bladder cancer

Bladder cancer has the highest recurrence rate of any malignancy (ie, 70% within 5 y). Although most patients with bladder cancer can be treated initially with organ-sparing therapy, most experience either recurrence or progression. The underlying genetic changes that result in a bladder tumor occur in the entire urothelium, making the whole lining of the urinary system susceptible to tumor recurrence.

Risk factors for recurrence and progression include the following[61, 62] :

  • Female sex
  • Larger tumor size
  • Multifocality
  • Larger number of tumors
  • High tumor grade
  • Advanced stage
  • Presence of CIS

The time interval to recurrence is also significant. Patients with tumor recurrences within 2 years, and especially with recurrences within 3-6 months, have an aggressive tumor and an increased risk of disease progression.

Previous
 
 
Contributor Information and Disclosures
Author

Gary David Steinberg, MD, FACS The Bruce and Beth White Family Professor and Vice Chairman of Urology, Director of Urologic Oncology, Section of Urology, Department of Surgery, The University of Chicago Medical Center and Cancer Center

Gary David Steinberg, MD, FACS is a member of the following medical societies: American Association for Cancer Research, Society of Laparoendoscopic Surgeons, American Society of Clinical Oncology, Societe Internationale d'Urologie (International Society of Urology), American College of Surgeons, American Urological Association, Society of Urologic Oncology

Disclosure: Received consulting fee from Abbott Molecular for consulting; Received consulting fee from Endo Pharmaceuticals for consulting; Received consulting fee from Bioniche for consulting; Received consulting fee from Tengion for consulting; Received consulting fee from Archimedes for review panel membership; Received consulting fee from PhotoCure for review panel membership; Received consulting fee from Taris Biomedical for review panel membership; Received none from Cold Genesys for other; Received h for: Photocure; Taris Biomedical; Heat Biologics: Cold Genesys; Merck; Roche/Genentech; Karl Storz; Mdx Health, Telesta.

Coauthor(s)

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.

Bagi RP Jana, MD Associate Professor of Medicine (Genitourinary Oncology), Division of Hematology and Oncology, University of Texas Medical Branch

Bagi RP Jana, MD is a member of the following medical societies: American Cancer Society, American Medical Association, SWOG, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Chief Editor

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Acknowledgements

Sujeet S Acharya, MD Resident Physician, Department of Surgery, Section of Urology, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Disclosure: Nothing to disclose.

Brendan Curti, MD Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center

Brendan Curti, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, Oregon Medical Association, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Edward M Gong, MD Fellow, Department of Surgery, Division of Urology, Children's Hospital Boston

Disclosure: Nothing to disclose.

Mark H Katz, MD Fellow in Urologic Oncology and Minimally Invasive Surgery, University of Chicago Medical Center

Mark H Katz, MD is a member of the following medical societies: Alpha Omega Alpha, American Urological Association, Endourological Society, and Society of Urologic Oncology

Disclosure: Nothing to disclose.

Hyung L Kim, MD Associate Professor, Cedars-Sinai Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

References
  1. Kantor AF, Hartge P, Hoover RN, Fraumeni JF Jr. Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder. Cancer Res. 1988 Jul 1. 48(13):3853-5. [Medline].

  2. Escudero DO, Shirodkar SP, Lokeshwar VB. Bladder Carcinogenesis and Molecular Pathways. Lokeshwar VB. Bladder Tumors: Molecular Aspects and Clinical Management. New York: Springer Science; 2010. 23-41.

  3. Spruck CH 3rd, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Miyao N, Tsai YC, et al. Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res. 1994 Feb 1. 54(3):784-8. [Medline].

  4. Trias I, Algaba F, Condom E, Español I, Seguí J, Orsola I, et al. Small cell carcinoma of the urinary bladder. Presentation of 23 cases and review of 134 published cases. Eur Urol. 2001 Jan. 39(1):85-90. [Medline].

  5. Bessette PL, Abell MR, Herwig KR. A clinicopathologic study of squamous cell carcinoma of the bladder. J Urol. 1974 Jul. 112(1):66-7. [Medline].

  6. Faysal MH. Squamous cell carcinoma of the bladder. J Urol. 1981 Nov. 126(5):598-9. [Medline].

  7. Lagwinski N, Thomas A, Stephenson AJ, Campbell S, Hoschar AP, El-Gabry E, et al. Squamous cell carcinoma of the bladder: a clinicopathologic analysis of 45 cases. Am J Surg Pathol. 2007 Dec. 31(12):1777-87. [Medline].

  8. El-Sebaie M, Zaghloul MS, Howard G, Mokhtar A. Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of etiological features, natural history, and management. Int J Clin Oncol. 2005 Feb. 10(1):20-5. [Medline].

  9. Heyns CF, van der Merwe A. Bladder cancer in Africa. Can J Urol. 2008 Feb. 15(1):3899-908. [Medline].

  10. Tomlinson DC, Baldo O, Harnden P, Knowles MA. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007 Sep. 213(1):91-8. [Medline]. [Full Text].

  11. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr. 16(2):139-49. [Medline].

  12. Fadl-Elmula I. Chromosomal changes in uroepithelial carcinomas. Cell Chromosome. 2005 Aug 7. 4:1. [Medline]. [Full Text].

  13. Knowles MA. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese?. Carcinogenesis. 2006 Mar. 27(3):361-73. [Medline].

  14. Salinas-Sánchez AS, Lorenzo-Romero JG, Giménez-Bachs JM, Sánchez-Sánchez F, Donate-Moreno MJ, Rubio-Del-Campo A, et al. Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: a long-term study. Urol Oncol. 2008 Nov-Dec. 26(6):620-6. [Medline].

  15. Miyamoto H, Shuin T, Ikeda I, Hosaka M, Kubota Y. Loss of heterozygosity at the p53, RB, DCC and APC tumor suppressor gene loci in human bladder cancer. J Urol. 1996 Apr. 155(4):1444-7. [Medline].

  16. Karam JA, Lotan Y, Karakiewicz PI, Ashfaq R, Sagalowsky AI, Roehrborn CG, et al. Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol. 2007 Feb. 8(2):128-36. [Medline].

  17. Campbell SC, Volpert OV, Ivanovich M, Bouck NP. Molecular mediators of angiogenesis in bladder cancer. Cancer Res. 1998 Mar 15. 58(6):1298-304. [Medline].

  18. Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M, et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A. 2009 Aug 18. 106(33):14016-21. [Medline]. [Full Text].

  19. Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C. Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol. 2006 Feb 10. 24(5):778-89. [Medline].

  20. Brennan P, Bogillot O, Cordier S, Greiser E, Schill W, Vineis P, et al. Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies. Int J Cancer. 2000 Apr 15. 86(2):289-94. [Medline].

  21. Fortuny J, Kogevinas M, Chang-Claude J, González CA, Hours M, Jöckel KH, et al. Tobacco, occupation and non-transitional-cell carcinoma of the bladder: an international case-control study. Int J Cancer. 1999 Jan 5. 80(1):44-6. [Medline].

  22. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011 Aug 17. 306(7):737-45. [Medline]. [Full Text].

  23. Cumberbatch MG, Cox A, Teare D, Catto JW. Contemporary Occupational Carcinogen Exposure and Bladder Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2015 Dec. 1 (9):1282-90. [Medline].

  24. Baris D, Waddell R, Beane Freeman LE, Schwenn M, Colt JS, et al. Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic. J Natl Cancer Inst. 2016 Sep. 108 (9):[Medline].

  25. Nelson R. Arsenic-Contaminated Well Water Boosts Bladder Cancer Risk. Medscape Medical News. Available at http://www.medscape.com/viewarticle/862914. May 5, 2016; Accessed: May 7, 2016.

  26. Stein JP, Skinner EC, Boyd SD, Skinner DG. Squamous cell carcinoma of the bladder associated with cyclophosphamide therapy for Wegener's granulomatosis: a report of 2 cases. J Urol. 1993 Mar. 149(3):588-9. [Medline].

  27. Figueroa JD, Koutros S, Colt JS, Kogevinas M, Garcia-Closas M, et al. Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms. J Natl Cancer Inst. 2015 Nov. 107 (11):[Medline].

  28. El-Bolkainy MN, Mokhtar NM, Ghoneim MA, Hussein MH. The impact of schistosomiasis on the pathology of bladder carcinoma. Cancer. 1981 Dec 15. 48(12):2643-8. [Medline].

  29. Botelho M, Ferreira AC, Oliveira MJ, Domingues A, Machado JC, da Costa JM. Schistosoma haematobium total antigen induces increased proliferation, migration and invasion, and decreases apoptosis of normal epithelial cells. Int J Parasitol. 2009 Aug. 39(10):1083-91. [Medline].

  30. Ahmad I, Barnetson RJ, Krishna NS. Keratinizing squamous metaplasia of the bladder: a review. Urol Int. 2008. 81(3):247-51. [Medline].

  31. Khan MS, Thornhill JA, Gaffney E, Loftus B, Butler MR. Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience. Eur Urol. 2002 Nov. 42(5):469-74. [Medline].

  32. Newman DM, Brown JR, Jay AC, Pontius EE. Squamous cell carcinoma of the bladder. J Urol. 1968 Oct. 100(4):470-3. [Medline].

  33. Faysal MH, Freiha FS. Primary neoplasm in vesical diverticula. A report of 12 cases. Br J Urol. 1981 Apr. 53(2):141-3. [Medline].

  34. Yurdakul T, Avunduk MC, Piskin MM. Pure squamous cell carcinoma after intravesical BCG treatment. A case report. Urol Int. 2005. 74(3):283-5. [Medline].

  35. STUART WT. Carcinoma of the bladder associated with exstrophy. Report of a case and review of the literature. Va Med Mon (1918). 1962 Jan. 89:39-42. [Medline].

  36. Ribeiro JC, Silva C, Sousa L, García P, Santos A. [Squamous cell carcinoma in bladder extrophy]. Actas Urol Esp. 2005 Jan. 29(1):110-2. [Medline].

  37. Gupta S, Gupta IM. Ectopia vesicae complicated by squamous cell carcinoma. Br J Urol. 1976 Aug. 48(4):244. [Medline].

  38. Rieder JM, Parsons JK, Gearhart JP, Schoenberg M. Primary squamous cell carcinoma in unreconstructed exstrophic bladder. Urology. 2006 Jan. 67(1):199. [Medline].

  39. Sheldon CA, Clayman RV, Gonzalez R, Williams RD, Fraley EE. Malignant urachal lesions. J Urol. 1984 Jan. 131(1):1-8. [Medline].

  40. Lin RY, Rappoport AE, Deppisch LM, Natividad NS, Katz W. Squamous cell carcinoma of the urachus. J Urol. 1977 Dec. 118(6):1066-7. [Medline].

  41. SHAW RE. Squamous-cell carcinoma in a cyst of the urachus. Br J Urol. 1958 Mar. 30(1):87-9. [Medline].

  42. Chow YC, Lin WC, Tzen CY, Chow YK, Lo KY. Squamous cell carcinoma of the urachus. J Urol. 2000 Mar. 163(3):903-4. [Medline].

  43. Fujiyama C, Nakashima N, Tokuda Y, Uozumi J. Squamous cell carcinoma of the urachus. Int J Urol. 2007 Oct. 14(10):966-8. [Medline].

  44. Cancer Facts & Figures 2016. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed: May 7, 2016.

  45. [Guideline] NCCN Clinical Practice Guidelines in Oncology. Bladder Cancer, Version 1.2016. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed: May 9, 2016.

  46. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb. 62(1):10-29. [Medline].

  47. Dawson C, Whitfield H. ABC of Urology. Urological malignancy--II: Urothelial tumours. BMJ. 1996 Apr 27. 312(7038):1090-4. [Medline]. [Full Text].

  48. Abrahams NA, Moran C, Reyes AO, Siefker-Radtke A, Ayala AG. Small cell carcinoma of the bladder: a contemporary clinicopathological study of 51 cases. Histopathology. 2005 Jan. 46(1):57-63. [Medline].

  49. Lohrisch C, Murray N, Pickles T, Sullivan L. Small cell carcinoma of the bladder: long term outcome with integrated chemoradiation. Cancer. 1999 Dec 1. 86(11):2346-52. [Medline].

  50. Gouda I, Mokhtar N, Bilal D, El-Bolkainy T, El-Bolkainy NM. Bilharziasis and bladder cancer: a time trend analysis of 9843 patients. J Egypt Natl Canc Inst. 2007 Jun. 19(2):158-62. [Medline].

  51. Felix AS, Soliman AS, Khaled H, Zaghloul MS, Banerjee M, El-Baradie M, et al. The changing patterns of bladder cancer in Egypt over the past 26 years. Cancer Causes Control. 2008 May. 19(4):421-9. [Medline].

  52. Elsobky E, El-Baz M, Gomha M, Abol-Enein H, Shaaban AA. Prognostic value of angiogenesis in schistosoma-associated squamous cell carcinoma of the urinary bladder. Urology. 2002 Jul. 60(1):69-73. [Medline].

  53. Griffiths TR, Charlton M, Neal DE, Powell PH. Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without maintenance. J Urol. 2002 Jun. 167(6):2408-12. [Medline].

  54. Pycha A, Mian C, Posch B, Haitel A, Mokhtar AA, El-Baz M, et al. Numerical chromosomal aberrations in muscle invasive squamous cell and transitional cell cancer of the urinary bladder: an alternative to classic prognostic indicators?. Urology. 1999 May. 53(5):1005-10. [Medline].

  55. Shaaban AA, Javadpour N, Tribukait B, Ghoneim MA. Prognostic significance of flow-DNA analysis and cell surface isoantigens in carcinoma of bilharzial bladder. Urology. 1992 Mar. 39(3):207-10. [Medline].

  56. Ghoneim MA, Ashamallah AK, Awaad HK, Whitmore WF Jr. Randomized trial of cystectomy with or without preoperative radiotherapy for carcinoma of the bilharzial bladder. J Urol. 1985 Aug. 134(2):266-8. [Medline].

  57. Cheng L, Pan CX, Yang XJ, Lopez-Beltran A, MacLennan GT, Lin H, et al. Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients. Cancer. 2004 Sep 1. 101(5):957-62. [Medline].

  58. Shahab N. Extrapulmonary small cell carcinoma of the bladder. Semin Oncol. 2007 Feb. 34(1):15-21. [Medline].

  59. Mackey JR, Au HJ, Hugh J, Venner P. Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J Urol. 1998 May. 159(5):1624-9. [Medline].

  60. Choong NW, Quevedo JF, Kaur JS. Small cell carcinoma of the urinary bladder. The Mayo Clinic experience. Cancer. 2005 Mar 15. 103(6):1172-8. [Medline].

  61. van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, et al. 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].

  62. Fernandez-Gomez J, Solsona E, Unda M, Martinez-Piñeiro L, Gonzalez M, Hernandez R, et al. Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: multivariate analysis of data from four randomized CUETO trials. Eur Urol. 2008 May. 53(5):992-1001. [Medline].

  63. Cha EK, Tirsar LA, Schwentner C, Christos PJ, Mian C, Hennenlotter J, et al. Immunocytology is a strong predictor of bladder cancer presence in patients with painless hematuria: a multicentre study. Eur Urol. 2012 Jan. 61(1):185-92. [Medline].

  64. Strittmatter F, Buchner A, Karl A, Sommer ML, Straub J, Tilki D, et al. Individual learning curve reduces the clinical value of urinary cytology. Clin Genitourin Cancer. 2011 Sep. 9(1):22-6. [Medline].

  65. Lotan Y, Roehrborn CG. Cost-effectiveness of a modified care protocol substituting bladder tumor markers for cystoscopy for the followup of patients with transitional cell carcinoma of the bladder: a decision analytical approach. J Urol. 2002 Jan. 167(1):75-9. [Medline].

  66. Apolo AB, Vogelzang NJ, Theodorescu D. New and promising strategies in the management of bladder cancer. Am Soc Clin Oncol Educ Book. 2015. 35:105-12. [Medline]. [Full Text].

  67. Grossfeld GD, Litwin MS, Wolf JS Jr, Hricak H, Shuler CL, Agerter DC, et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy--part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology. 2001 Apr. 57(4):604-10. [Medline].

  68. Murphy WM, Crabtree WN, Jukkola AF, Soloway MS. The diagnostic value of urine versus bladder washing in patients with bladder cancer. J Urol. 1981 Sep. 126(3):320-2. [Medline].

  69. Lokeshwar VB, Soloway MS. Current bladder tumor tests: does their projected utility fulfill clinical necessity?. J Urol. 2001 Apr. 165(4):1067-77. [Medline].

  70. Grossman HB, Soloway M, Messing E, Katz G, Stein B, Kassabian V, et al. Surveillance for recurrent bladder cancer using a point-of-care proteomic assay. JAMA. 2006 Jan 18. 295(3):299-305. [Medline].

  71. Al-Sukhun S, Hussain M. Molecular biology of transitional cell carcinoma. Crit Rev Oncol Hematol. 2003 Aug. 47(2):181-93. [Medline].

  72. Halling KC, Kipp BR. Bladder cancer detection using FISH (UroVysion assay). Adv Anat Pathol. 2008 Sep. 15(5):279-86. [Medline].

  73. Soloway MS, Briggman V, Carpinito GA, Chodak GW, Church PA, Lamm DL, et al. Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol. 1996 Aug. 156(2 Pt 1):363-7. [Medline].

  74. van Rhijn BW, van der Poel HG, van der Kwast TH. Urine markers for bladder cancer surveillance: a systematic review. Eur Urol. 2005 Jun. 47 (6):736-48. [Medline].

  75. [Guideline] Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Compérat E, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol. 2013 Oct. 64 (4):639-53. [Medline]. [Full Text].

  76. Hall MC, Chang SS, Dalbagni G, Pruthi RS, Seigne JD, Skinner EC, et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol. 2007 Dec. 178(6):2314-30. [Medline].

  77. Greene LF, Page DL, Fleming D, et al. American Joint Committee on Cancer (AJCC) Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002.

  78. [Guideline] Stenzl A, Cowan NC, De Santis M, Jakse G, Kuczyk MA, Merseburger AS, et al. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2009 Apr. 55(4):815-25. [Medline].

  79. Chedgy EC, Black PC. Radical Cystectomy and the Multidisciplinary Management of Muscle-Invasive Bladder Cancer. JAMA Oncol. 2016 May 5. [Medline]. [Full Text].

  80. Mitin T. Rethinking Radical Cystectomy as the Best Choice for Most Patients With Muscle-Invasive Bladder Cancer. JAMA Oncol. 2016 May 5. [Medline]. [Full Text].

  81. Teo MT, Dyrskjøt L, Nsengimana J, Buchwald C, Snowden H, Morgan J, et al. Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer. Ann Oncol. 2014 Apr. 25 (4):877-83. [Medline]. [Full Text].

  82. Serretta V, Galuffo A, Pavone C, Allegro R, Pavone-MacAluso M. Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of bladder: Phase I-II study on marker lesions. Urology. 2005 Jan. 65(1):65-9. [Medline].

  83. Sylvester RJ, van der Meijden AP, Witjes JA, Kurth K. Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials. J Urol. 2005 Jul. 174(1):86-91; discussion 91-2. [Medline].

  84. Witjes JA, Hendricksen K. Intravesical pharmacotherapy for non-muscle-invasive bladder cancer: a critical analysis of currently available drugs, treatment schedules, and long-term results. Eur Urol. 2008 Jan. 53(1):45-52. [Medline].

  85. Zaharoff DA, Hoffman BS, Hooper HB, Benjamin CJ Jr, Khurana KK, Hance KW, et al. Intravesical immunotherapy of superficial bladder cancer with chitosan/interleukin-12. Cancer Res. 2009 Aug 1. 69(15):6192-9. [Medline]. [Full Text].

  86. Islam MA, Bhuiyan ZH, Shameem IA. Intravesical adjuvant therapy using mitomycin C. Mymensingh Med J. 2006 Jan. 15(1):40-4. [Medline].

  87. Herr HW, Dalbagni G, Donat SM. Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer. Eur Urol. 2011 Jul. 60(1):32-6. [Medline].

  88. Schmidbauer J, Witjes F, Schmeller N, Donat R, Susani M, Marberger M. Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy. J Urol. 2004 Jan. 171(1):135-8. [Medline].

  89. Jichlinski P, Guillou L, Karlsen SJ, Malmström PU, Jocham D, Brennhovd B, et al. Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study. J Urol. 2003 Jul. 170(1):226-9. [Medline].

  90. Hungerhuber E, Stepp H, Kriegmair M, Stief C, Hofstetter A, Hartmann A, et al. Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology. 2007 Feb. 69(2):260-4. [Medline].

  91. Kausch I, Sommerauer M, Montorsi F, Stenzl A, Jacqmin D, Jichlinski P, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol. 2010 Apr. 57(4):595-606. [Medline].

  92. Waknine Y. FDA Approves Cysview for Cystoscopic Detection of Papillary Bladder Cancer. Medscape Medical News, June 4, 2010. Available at http://www.medscape.com/viewarticle/722923. Accessed: January 10, 2013.

  93. Booth CM, Tannock IF. Benefits of Adjuvant Chemotherapy for Bladder Cancer. JAMA Oncol. 2015 Sep. 1 (6):727-8. [Medline].

  94. Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer. ClinicalTrials.gov. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT01224665. Accessed: January 4, 2013.

  95. Mukesh M, Cook N, Hollingdale AE, Ainsworth NL, Russell SG. Small cell carcinoma of the urinary bladder: a 15-year retrospective review of treatment and survival in the Anglian Cancer Network. BJU Int. 2009 Mar. 103(6):747-52. [Medline].

  96. Ehdaie B, Maschino A, Shariat SF, Rioja J, Hamilton RJ, Lowrance WT, et al. Comparative outcomes of pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation in patients treated with radical cystectomy. J Urol. 2012 Jan. 187(1):74-9. [Medline].

  97. Brinkman MT, Karagas MR, Zens MS, Schned A, Reulen RC, Zeegers MP. Minerals and vitamins and the risk of bladder cancer: results from the New Hampshire Study. Cancer Causes Control. 2010 Apr. 21(4):609-19. [Medline]. [Full Text].

  98. O'Donnell MA, Lilli K, Leopold C. Interim results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alfa-2b for superficial bladder cancer. J Urol. 2004 Sep. 172(3):888-93. [Medline].

  99. Nepple KG, Lightfoot AJ, Rosevear HM, O'Donnell MA, Lamm DL. Bacillus Calmette-Guérin with or without interferon a-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer. J Urol. 2010 Nov. 184(5):1915-9. [Medline].

  100. Kamat AM, Dickstein RJ, Messetti F, Anderson R, Pretzsch SM, Gonzalez GN, et al. Use of fluorescence in situ hybridization to predict response to bacillus Calmette-Guérin therapy for bladder cancer: results of a prospective trial. J Urol. 2012 Mar. 187(3):862-7. [Medline]. [Full Text].

  101. Barlow L, McKiernan JM, Benson MC. Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle invasive bladder cancer after previous bacillus Calmette-Guérin therapy. J Urol. 2013 Mar. 189(3):834-9. [Medline].

  102. Schmidbauer J, Witjes F, Schmeller N, Donat R, Susani M, Marberger M. Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy. J Urol. 2004 Jan. 171(1):135-8. [Medline].

  103. Jichlinski P, Guillou L, Karlsen SJ, Malmström PU, Jocham D, Brennhovd B, et al. Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study. J Urol. 2003 Jul. 170(1):226-9. [Medline].

  104. Hungerhuber E, Stepp H, Kriegmair M, Stief C, Hofstetter A, Hartmann A, et al. Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology. 2007 Feb. 69(2):260-4. [Medline].

  105. Fradet Y, Grossman HB, Gomella L, Lerner S, Cookson M, Albala D, et al. A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol. 2007 Jul. 178(1):68-73; discussion 73. [Medline].

  106. Jocham D, Witjes F, Wagner S, Zeylemaker B, van Moorselaar J, Grimm MO, et al. Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol. 2005 Sep. 174(3):862-6; discussion 866. [Medline].

  107. Stenzl A, Burger M, Fradet Y, Mynderse LA, Soloway MS, Witjes JA, et al. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol. 2010 Nov. 184(5):1907-13. [Medline].

  108. Hermann GG, Mogensen K, Carlsson S, Marcussen N, Duun S. Fluorescence-guided transurethral resection of bladder tumours reduces bladder tumour recurrence due to less residual tumour tissue in Ta/T1 patients: a randomized two-centre study. BJU Int. 2011 Oct. 108(8 Pt 2):E297-303. [Medline].

  109. Tilki D, Reich O, Svatek RS, Karakiewicz PI, Kassouf W, Novara G, et al. Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients. J Urol. 2010 May. 183(5):1757-63. [Medline].

  110. Davis JW, Castle EP, Pruthi RS, Ornstein DK, Guru KA. Robot-assisted radical cystectomy: an expert panel review of the current status and future direction. Urol Oncol. 2010 Sep-Oct. 28(5):480-6. [Medline].

  111. Chang SS, Cookson MS. Radical cystectomy for bladder cancer: the case for early intervention. Urol Clin North Am. 2005 May. 32(2):147-55. [Medline].

  112. Sánchez-Ortiz RF, Huang WC, Mick R, Van Arsdalen KN, Wein AJ, Malkowicz SB. An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol. 2003 Jan. 169(1):110-5; discussion 115. [Medline].

  113. Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT01224665. Accessed: November 13, 2012.

  114. Raghavan D, Burgess E, Gaston KE, Haake MR, Riggs SB. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer. Semin Oncol. 2012 Oct. 39(5):588-97. [Medline].

  115. Winquist E, Kirchner TS, Segal R, Chin J, Lukka H. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004 Feb. 171(2 Pt 1):561-9. [Medline].

  116. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28. 349(9):859-66. [Medline].

  117. Herr HW, Faulkner JR, Grossman HB, Natale RB, deVere White R, Sarosdy MF, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol. 2004 Jul 15. 22(14):2781-9. [Medline].

  118. Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1. 29(16):2171-7. [Medline]. [Full Text].

  119. Mooso BA, Vinall RL, Mudryj M, Yap SA, deVere White RW, Ghosh PM. The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence. J Urol. 2015 Jan. 193 (1):19-29. [Medline].

  120. Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan. 16 (1):76-86. [Medline].

  121. Saxman SB, Propert KJ, Einhorn LH, Crawford ED, Tannock I, Raghavan D, et al. Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1997 Jul. 15(7):2564-9. [Medline].

  122. Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan. 42(1):50-4. [Medline].

  123. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20. 23(21):4602-8. [Medline].

  124. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20. 23(21):4602-8. [Medline].

  125. Iwasaki K, Obara W, Kato Y, Takata R, Tanji S, Fujioka T. Neoadjuvant gemcitabine plus carboplatin for locally advanced bladder cancer. Jpn J Clin Oncol. 2013 Feb. 43(2):193-9. [Medline].

  126. Bellmunt J, Théodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Sep 20. 27(27):4454-61. [Medline].

  127. Ploeg M, Kums AC, Aben KK, van Lin EN, Smits G, Vergunst H, et al. Prognostic factors for survival in patients with recurrence of muscle invasive bladder cancer after treatment with curative intent. Clin Genitourin Cancer. 2011 Sep. 9(1):14-21. [Medline].

  128. Bruins HM, Djaladat H, Ahmadi H, Sherrod A, Cai J, Miranda G, et al. Incidental cancer of the prostate in patients with bladder urothelial carcinoma: comprehensive analysis of 1476 radical cystoprostatectomy specimens. J Urol. 2013 May 23. [Medline].

  129. Zehnder P, Studer UE, Daneshmand S, et al. Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node-positive bladder cancer who are unfit for or who decline adjuvant chemotherapy. BJU Int. 2014 Apr. 113(4):554-60. [Medline].

  130. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 Mar 4. [Medline].

 
Previous
Next
 
In an ileal conduit, a small segment of ileum is taken out of continuity with the gastrointestinal tract but is maintained on its mesentery. Ureters are anastomosed to one end of this ileal segment, and the other end is brought out as a stoma to the abdominal wall.
In an Indiana pouch, a urinary reservoir is created from detubularized right colon and an efferent limb of terminal ileum. Terminal ileum is plicated and brought to the abdominal wall. The continence mechanism is the ileocecal valve.
In an orthotopic neobladder, a segment of ileum is used to construct a neobladder, which is connected to the urethra. Orthotopic neobladder most closely restores the natural storage and voiding function of the native bladder.
The classic appearance of carcinoma in situ as a flat, velvety patch. However, using special staining techniques such as 5-aminolevulinic acid, it has been shown that significant areas of carcinoma in situ are easily overlooked by conventional cystoscopy. Courtesy of Abbott and Vysis Inc.
Papillary bladder tumors such as this one are typically of low stage and grade (Ta-G1). Courtesy of Abbott and Vysis Inc.
Sessile lesions as shown usually invade muscle, although occasionally a tumor is detected at the T1-G3 stage prior to muscle invasion. Courtesy of Abbott and Vysis Inc.
Photograph in which fluorescence in situ hybridization centromere staining identifies aneuploidy of chromosome 3. Multiple instances of overexpression of the chromosome (note the multiple red dots, which identify centromeres of this chromosome) prove aneuploidy.
Cross-section through the bladder, uterus, and vagina with squamous cell carcinoma of the bladder infiltrating through the bladder wall into the vaginal wall.
High power, Pap stain showing high grade urothelial carcinoma on a bladder wash cytology.
Intermediate power, H and E stain of urothelial carcinoma in situ. The superficial cells shed into the urine and correlate with those seen in cytologic bladder washing or urine cytology.
High power, H and E stain of high grade urothelial carcinoma. This tumor is now invasive into the muscularis propria (smooth muscle seen in center of image).
Histopathology of bladder shows eggs of Schistosoma haematobium surrounded by intense infiltrates of eosinophils and other inflammatory cells.
(A) When infused into the bladder, the optical imaging agent hexaminolevulinate (Cysview) accumulates preferentially in malignant cells. (B) On blue-light cystoscopy, the collection of hexaminolevulinate within tumors is visible as bright red spots. Courtesy of Gary David Steinberg, MD, FACS.
Table 1. Clinical Findings and Recommended Action in Patients with Negative Cystoscopy
Cystoscopy Findings Urine Cytology Findings FISH* Findings Action
Negative Negative Negative† Routine follow-up
Negative Negative Positive‡ Increased frequency of surveillance, whether FISH findings are false positive or anticipatory positive
Negative Positive Negative or positive Cancer until proven otherwise
  • Upper tract imaging with contrast
  • Cystoscopy with retrograde pyelography, washings, and/or ureteroscopy
  • Evaluate urethra
  • Increased frequency of surveillance upon negative findings
*FISH - Fluorescent in situ hybridization.



†Negative predictive value 95%.



‡Positive predictive value 30%.



Table 2. Recurrence and Progression Rates at 5 Years for Ta, T1, and CIS TCC of the Bladder Treated With BCG
Stage Recurrence, % Progression, %
Ta 55 11
T1 61 31
CIS 45 23
G1 61 2-4
G2 56 5-7
G3 50-70 30-40
Table 3. Most Common Complications of Radical Cystectomy
Early Complications Rate, % Late Complications Rate, %
Ileus 10 Small-bowel obstruction 7.4
Wound infection 5.5 Ureteroenteric stricture 7.0
Sepsis 4.9 Renal calculi 3.9
Pelvic abscess 4.7 Acute pyelonephritis 3.1
Hemorrhage 3.4 Parastomal hernia 2.8
Wound dehiscence 3.3 Stomal stenosis 2.8
Bowel obstruction 3.0 Incisional hernia 2.2
Enterocutaneous fistula 2.2 Fistula 1.3
Rectal injury 2.2 Rectal complications < 1
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.