Diagnostic Considerations

The presentation in bladder cancer may resemble a urinary tract infection (UTI), or the 2 conditions may coexist. Both UTIs and bladder cancer can cause hematuria, and bacteriuria occurs in about 50% of patients with squamous cell carcinoma (SCC). Patients with bladder cancer may have spontaneous resolution of gross or microscopic hematuria, which may lull the patient and the clinician into erroneously believing that no significant entity is present. UTIs are usually associated with irritative voiding symptoms (eg, dysuria, frequency, urgency). However, around 80% of patients who have carcinoma in situ (CIS) will also present with irritative voiding symptoms. ^[64]

CIS is often misdiagnosed as a bladder infection and treated as such. Patients with irritative voiding symptoms that do not resolve with treatment for UTI require further evaluation. The investigation should include urine cultures for fungi and tuberculosis, as well as cytology studies.

The first step in a bladder cancer workup involves the patient undergoing cystoscopy in an office setting. Cystoscopy in patients with CIS may reveal a characteristic red, velvety appearance that resembles an area of inflammation. In some cases, however, CIS is not visible on gross inspection. If there is a suspicious area or visible tumor a biopsy or resection should be done during repeat cystoscopy performed in the operating room. ^[64]

Diagnostic tests include a urine cytology test and/or tests for one of several available bladder cancer markers. These tests are highly sensitive in detecting CIS. Bladder biopsies are needed to firmly establish a diagnosis. Urinary cytology is highly specific for urothelial bladder cancer, with improved sensitivity for high-grade tumors and cytology obtained by bladder wash or barbotage.

Unfortunately, urinary cytology is not especially helpful in early diagnosis of SCCs. Most of these tumors are not diagnosed until they are at an advanced stage.

With small cell carcinoma, the main differential diagnoses are high-grade urothelial carcinoma, lymphoma, and sarcoma. Additionally, metastatic small cell carcinoma should be ruled out based on the available clinical information. Because small cell carcinoma of the urinary bladder is often mixed with urothelial carcinoma and because any presence of small cell carcinoma is justifiable to render the diagnosis, it is important to thoroughly examine the tumor tissue.

Differential Diagnoses

Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females
Hemorrhagic Cystitis: Noninfectious
Nephrolithiasis
Renal Cell Carcinoma
Renal Transitional Cell Carcinoma
Ureteral Trauma
Urinary Tract Infection (UTI) in Males

Workup

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Media Gallery

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.
Bladder cancer. The classic appearance of carcinoma in situ is 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.
Bladder cancer. Papillary bladder tumors such as this one are typically of low stage and grade (Ta-G1). Courtesy of Abbott and Vysis Inc.
Bladder cancer. 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.
Bladder cancer. 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.
Bladder cancer. Cross-section through the bladder, uterus, and vagina with squamous cell carcinoma of the bladder infiltrating through the bladder wall into the vaginal wall.
Bladder cancer. High power, Pap stain showing high grade urothelial carcinoma on a bladder wash cytology.
Bladder cancer, Intermediate power, H&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.
Bladder cancer. High power, H&E stain of high grade urothelial carcinoma. This tumor is now invasive into the muscularis propria (smooth muscle seen in center of image).
Bladder cancer. Histopathology of bladder shows eggs of Schistosoma haematobium surrounded by intense infiltrates of eosinophils and other inflammatory cells.
Bladder cancer. (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.

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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 random bladder and urethral biopsies, retrograde pyelography, selective ureteral 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

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Author

Kara N Babaian, MD, FACS Assistant Professor, Director of Urologic Oncology, Division of Urology, Southern Illinois University School of Medicine

Kara N Babaian, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society of Clinical Oncology, American Urological Association, European Association of Urology, North Central Section of the American Urological Association (AUA), Society of Urologic Oncology, Society of Women in Urology

Disclosure: Participation in a clinical trial for: Janssen.

Coauthor(s)

Parker G Adams, BS DO Candidate, Kansas City University of Medicine and Biosciences College of Osteopathic Medicine

Parker G Adams, BS is a member of the following medical societies: American Urological Association

Disclosure: Nothing to disclose.

Courtney McClure, DO Resident Physician, Department of Urology, Ascension Healthcare

Disclosure: Nothing to disclose.

Brandon Tompkins, BS DO Candidate, Kansas City University of Medicine and Biosciences College of Osteopathic Medicine

Disclosure: Nothing to disclose.

Megan McMurray, DO Resident Physician, Department of Urology, Southern Illinois University School of Medicine

Megan McMurray, DO is a member of the following medical societies: American Association of Clinical Urologists, American Urological Association, Association of Women Surgeons, Society of Women in Urology

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, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoscopic and Robotic Surgeons, Society of University Urologists

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Endourological Society Board of Directors; President Elect North Central Section of the American Urological Association<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cook Medical.

Additional Contributors

Gary D Steinberg, MD, FACS Professor and Director, Perlmutter Cancer Center, Goldstein Bladder Cancer Program, NYU Langone Health, NYU Urology Associates

Gary D Steinberg, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Society of Clinical Oncology, American Urological Association, International Society of Urology, Society of Laparoscopic and Robotic Surgeons, Society of Urologic Oncology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Heat Biologics; CG Oncology; PhotoCure; Merck; Roche/Genentech; Ciclomed; Taris Biomedical (now Janssen); MDxHealth; Fidia Farmaceuticals; Urogen, Ferring; Aduro; Boston Scientific; Bristol Myers Squibb; Astra Zeneca; Pfizer, Janssen; others<br/>Member of Clinical Trial Protocol Committees for: for: Merck; BMS; Janssen; CG Oncology; Pfizer; PhotoCure; Fidia; Seagen; Protara.

Kush Sachdeva, MD Southern Oncology and Hematology Associates, Inspira Health Network

Disclosure: Nothing to disclose.

Bagi RP Jana, MD, MBA, MHA, FACP Professor of Cancer Medicine, MD Anderson Cancer Center; Professor of Medicine, University of Texas Medical Branch at Galveston

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

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