eMedicine Specialties > Urology > Cancer, Bladder, Penis, and Urethra

Cystectomy, Partial: Workup

Author: Jason T Jankowski, MD, Staff Physician, Department of Urology, University Hospitals of Cleveland, Case Western Reserve University
Coauthor(s): Edward E Cherullo, MD, Assistant Professor, Department of Urology, Case Western Reserve University School of Medicine; Matthew L Steinway, MD, Staff Physician, Department of Urology, University Hospitals of Cleveland, Case Western Reserve University; Adrian H Feng, MD, Consulting Staff, Department of Urology, Urology Associates LTD
Contributor Information and Disclosures

Updated: Jan 14, 2008

Workup

Laboratory Studies

Laboratory evaluation is performed for diagnosis and surgical preparation. Diagnostic laboratory evaluation for urothelial cancer includes urinalysis, cytology, and urinary tumor marker levels.

  • Urinalysis can be used to detect microscopic and gross hematuria.
  • Conventional microscopic urine cytology may reveal tumor cells. Limitations of cytology include a false-negative rate of approximately 20%. Low-grade well-differentiated tumors can appear cytologically normal, accounting for some of this low specificity. In addition, well-differentiated tumors are thought to be more cohesive; thus, cytology has a lower yield. These two factors may account for the significant false-negative rate in cytological testing. The false-positive rate is approximately 1-12%, mostly because of urothelial atypia, inflammation, or changes associated with chemotherapy or radiation.
  • Recently, other urinary tumor markers associated with urothelial neoplasia have been developed and studied. These include the bladder tumor antigen (BTA) stat test, BTA TRAK test, nuclear matrix protein 22 (NMP-22), fibrin degradation products (FDPs), telomerase, hyaluronic acid, cytokeratins, DNA aneuploidy, Lewis X antigen expression, vascular endothelial growth factor, fluorescent in situ hybridization (FISH), and immunocytology.
    • BTA assays are based on an antibody-detectable tumor marker that is used to detect BTA, a basement membrane antigen released when cancer cells are invading and breaking down basement membrane.
    • The BTA stat test is used to identify a protein similar to human complement factor H. Bladder cancer cells exhibit factor H, which interacts with complement C3b to inhibit the membrane attack complex and protects from immune attack.
    • NMP-22 is a nuclear matrix protein associated with DNA replication. Higher levels of NMP-22 have been found in the urine of patients with bladder cancer.
    • Bladder cancer cells produce vascular endothelial growth factor to support angiogenesis. This increases vessel wall permeability of blood and plasma proteins, such as plasminogen, fibrinogen, and other clotting factors. Escaped factors result in a fibrin clot that is broken down into FDPs, which are then released into the urine. Increased urinary levels of FDP have been observed in patients with bladder cancer.
    • FISH is a technique that involves fluorescently labeled DNA probes to assess cells for chromosomal alterations. FISH can be used to identify cells in the urine that have the chromosomal abnormalities consistent with transitional cell carcinoma. Studies of FISH reveal a sensitivity of 71-81% and a specificity of 94-96%.
  • Although most of the new urinary markers yield a better sensitivity than conventional urinary cytology, their specificity is not as good. A recent comparison of the urinary markers reported a sensitivity of 44% for cytology, 74% for BTA stat, 53% for NMP-22, 52% for FDPs, and 70% for telomerase. The study reported a specificity of 95% for cytology, 73% for BTA stat, 60% for NMP-22, 91% for FDPs, and 99% for telomerase. The nuclear matrix protein BLCA-4 is the newest urinary tumor marker being investigated. An early study reports that this marker yields a sensitivity of 96% and a specificity of 81-100%.14

The general preoperative medical condition of the patient and the possible presence of metastatic disease should be assessed.

  • Serum electrolytes help reveal any concomitant medical condition and help assess renal function.
  • Blood reserves and bleeding risk can be determined with the help of a complete blood count, prothrombin time, and activated partial thromboplastin time.
  • The presence of an infection can be investigated with a white blood cell count, urinalysis, and culture.
  • Liver function tests and alkaline phosphatase may indicate liver and bone metastases.

Imaging Studies

Routine studies performed for staging bladder cancer include chest radiography, intravenous pyelography (IVP), CT scanning of the abdomen and pelvis, bone scan, and liver function tests. Mandatory preoperative imaging focuses on diagnosing and staging bladder cancer. Staging evaluation is a valuable tool to help determine whether the patient has superficial or muscle-infiltrating disease.

  • Intravenous pyelography: IVP is required in all patients with cystoscopic evidence of bladder cancer. IVP enables evaluation of the collecting system of the kidneys, ureters, and bladder for any associated tumors. Retrograde pyelography during cystoscopy can serve as an alternative to IVP.
  • CT urography: In recent years, CT urography has become a viable option to image the upper urinary tract. Some studies indicate the sensitivity and specificity of CT scanning surpasses that of IVP. Furthermore, many patients undergo CT scanning of the abdomen and pelvis as part of their staging evaluation (see Staging); thus, the upper urinary tract may be evaluated in the same setting.
  • MRI
    • Gadolinium-enhanced and gadolinium-excreted MRI scans have also been used to image the renal pelvis and ureters. Whether MRI is as accurate as IVP or retrograde pyelography is currently under investigation.
    • MRI generally does not provide more information than a CT scan. If bone metastases are suspected, MRI is more sensitive for detection than a CT scan or a radionucleotide bone scan. Recent work on collecting system imaging with MRI is ongoing. In addition, recently published studies using ferumoxtran-10–enhanced MRI suggest that this modality may improve lymph node staging in patients with bladder cancer.
  • Ureteroscopy: ureteroscopy can help directly visualize and allow for biopsy of any suspicious lesion in the ureter or renal collecting system. However, ureteroscopy is invasive.
  • CT scanning
    • Aggressive imaging, such as CT scanning of the abdomen and pelvis and bone scans, is not necessary to evaluate superficial disease. These forms of imaging usually are reserved for documented invasive disease. CT scan itself may provide information regarding depth of tumor invasion, pelvic and paraaortic lymphadenopathy, and the presence of liver or adrenal metastases. CT scan may fail to detect nodal metastases in as many as 40% of patients. Liver metastases smaller than 2 cm in diameter likewise are difficult to detect. Also, CT scan can make only gross assessments of extravesical involvement.
    • Although CT scanning of the chest is the most sensitive in evaluating for pulmonary metastases, this modality CT reveals many lesions smaller than 1 cm in diameter that may represent calcified granulomas. Plain radiography of the chest is usually used instead because standard films usually reveal lesions larger than 1 cm.
  • Bone scanning: This is not commonly performed in patients with normal alkaline phosphatase levels but may be performed as a baseline from which to compare future bone scans.
  • Positron emission tomography (PET): Currently, PET scanning has a limited role in the evaluation of bladder cancer. PET scanning has shown promise in detecting lymph node metastasis or distant soft-tissue metastasis; however, because of the low urinary excretion of commonly used radioisotopes involved in PET scans, they are not yet helpful in the pelvic imaging of bladder cancer.

Diagnostic Procedures

  • Cystoscopy should be performed in all patients in whom bladder cancer is suggested.
  • Biopsy samples should be obtained from multiple sites (including the urethra) before partial cystectomy is considered.
  • Retrograde pyelography can be performed at the same time if findings from an IVP or CT urography are inconclusive to adequately evaluate the upper urinary tracts. With the advances in endoscopic equipment and fiberoptics, ureteroscopy has enabled direct visual inspection of any suggestive upper-tract lesions, with the ability to obtain a biopsy specimen and even treat superficial lesions.
  • Selective saline wash cytologies or brush biopsies may be performed for further evaluation of the upper tract.
  • Transurethral resection with superficial and deep-muscle biopsy is an important tool to evaluate the depth of invasion and tumor pathology. Bladder perforation and possible spillage of tumor cells outside of the bladder should be avoided. However, recent evidence suggests that, even with extraperitoneal or intraperitoneal perforation, the risk of extravesical tumor seeding is low.
  • Pelvic lymphadenectomy during cystectomy remains the most accurate way of determining disease in the lymphatic system. Primary regions of lymphatic spread of bladder cancer include the perivesical, hypogastric, obturator, external iliac, and presacral nodes. Boundaries of the lymphadenectomy include the iliac bifurcations, femoral canals, genitofemoral nerves, and the bladder pedicles. Lymphadenectomy may also provide a therapeutic benefit. Of the 10-40% of patients with lymph node metastases who present for radical cystectomy, 35-70% have only limited metastases and 10-35% may be cured with cystectomy and lymphadenectomy. Laparoscopic lymphadenectomy prior to primary tumor resection has not been standard practice.

Histologic Findings

Primary solitary bladder cancer is a common indication for consideration of partial cystectomy. More than 90% of bladder cancers are transitional cell carcinomas. Of these, 70% are papillary, 10% are nodular, and 20% are mixed. When confined to the urothelium, the cancer is called carcinoma in situ. The other 10% of tumors are composed predominantly of squamous cell carcinomas (3-7%) and adenocarcinomas (2%). Secondary metastatic disease in the bladder accounts for less than 1% of all bladder cancers.

Not uncommonly, multiple tumor types coexist in the same bladder. The most common combination is a high-grade papillary transitional cell carcinoma with carcinoma in situ. Elements of squamous cell carcinoma are also frequently found with transitional cell cancers. Adenocarcinomas and transitional cell carcinoma is a less common combination. Tumors that contain transitional cell elements are still classified as a transitional cell carcinoma.

Carcinoma in situ

Carcinoma in situ consists of poorly differentiated transitional cell carcinoma cells confined to the urothelium. Carcinoma in situ may be papillary or flat in architecture. These cells demonstrate poor intercellular cohesiveness; thus, urine cytopathology is a very sensitive test. Carcinoma in situ may be present in more than 25% of patients with high-grade superficial tumors and, thus, can exist concurrently with cancer found elsewhere in the bladder. When found, partial cystectomy is contraindicated.

Transitional cell carcinoma

Histopathology is used to grade bladder cancer tumors. No uniform grading system exists; most grading systems are based on the degree of anaplasia of the tumor cells. Usually, 3-4 grades are considered, corresponding to the level of cellular differentiation. Tumor grade strongly correlates with stage and prognosis.

Grades and descriptions of transitional cell carcinoma are as follows:

  • Grade 0 - Papilloma with fewer than 7 epithelial cell layers and no abnormalities in histology
  • Grade I - Well-differentiated thin fibrovascular stalks with a thickened urothelium that contain more than 7 cell layers and that exhibit slight anaplasia and pleomorphism; possible increased nuclear-to-cytoplasmic ratio and prominence of nuclear membrane; rare mitotic figures
  • Grade II - Moderately differentiated, wider fibrovascular core, greater cell disturbance with loss of cellular polarity, higher nuclear-to-cytoplasmic ratio, nuclear pleomorphism and prominent nucleoli, and more frequent mitotic figures
  • Grade III - Poorly differentiated, marked pleomorphism, high nuclear-to-cytoplasmic ratios, and frequent mitotic figures; cells that remain undifferentiated from basement membrane to surface

Squamous cell carcinoma

Histologically, squamous cell carcinomas are composed of keratinized islands that show various degrees of differentiation. Eccentric cellular aggregates known as squamous pearls also exist. Urinary cytopathology is less sensitive in detecting squamous cell carcinoma. Histologic tumor differentiation is less predictive of overall prognosis than it is for transitional cell carcinomas, although tumor stage shows a strong correlation with prognosis.

Adenocarcinoma

All histologic variants of enteric adenocarcinoma, including signet-ring and colloid variants, can be found in the bladder. Most adenocarcinomas are mucin-producing and are either papillary or solid in architecture. Signet-ring adenocarcinoma can produce linitis plastica of the bladder. Most adenocarcinomas are poorly differentiated and invasive upon presentation.

Staging

The American Joint Committee has designated staging based on the tumor, node, and metastases (TNM) classification.
  • The TNM system for the primary tumor (T) is as follows:
    • Stage TX - Primary tumor cannot be assessed
    • Stage T0 - No evidence of primary tumor
    • Stage Ta - Noninvasive papillary carcinoma
    • Stage Tis - Carcinoma in situ
    • Stage T1 - Invades subepithelial connective tissue
    • Stage T2a - Invades superficial muscle (inner half)
    • Stage T2b - Invades deep muscle (outer half)
    • Stage T3a - Microscopic invasion of perivesical tissue
    • Stage T3b - Macroscopic invasion of perivesical tissue
    • Stage T4a - Invades prostate, uterus, and vagina
    • Stage T4b - Invades pelvic sidewall and abdominal wall
  • The following is the TNM system for the regional lymph nodes (N). Note that regional lymph nodes are in the pelvis; all others are considered distant lymph nodes.
    • Stage NX - Regional lymph nodes cannot be assessed
    • Stage N0 - No regional lymph node metastasis
    • Stage N1 - Metastasis in a single lymph node, 2 cm or smaller in greatest dimension
    • Stage N2 - Metastasis in a single lymph node, larger than 2 cm but not larger than 5 cm in greatest dimension; or, multiple lymph nodes, none larger than 5 cm in greatest dimension
    • Stage N3 - Metastasis in a lymph node larger than 5 cm in greatest dimension
  • The TNM system for distant metastasis (M) is as follows:
    • Stage MX - Distant metastasis cannot be assessed
    • Stage M0 - No distant metastasis
    • Stage M1 - Distant metastasis

While overstaging is relatively uncommon, clinical understaging occurs in as many as 53% of patients.

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Workup: Cystectomy, Partial
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References
Further Reading
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Further Reading

For more information, see Medscape's Bladder Cancer Resource Center.

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Keywords

bladder cancer, partial cystectomy, cystectomy, transitional cell carcinoma, bladder sparing, urachal carcinoma, bladder diverticula, cystic hydatid disease, cavernous hemangioma, interstitial cystitis, colovesical fistula, vesicovaginal fistula, bladder endometriosis, urothelial cancer, urothelial malignancy, bladder carcinoma, segmental resection of the bladder

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Contributor Information and Disclosures

Author

Jason T Jankowski, MD, Staff Physician, Department of Urology, University Hospitals of Cleveland, Case Western Reserve University
Jason T Jankowski, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

Coauthor(s)

Edward E Cherullo, MD, Assistant Professor, Department of Urology, Case Western Reserve University School of Medicine
Edward E Cherullo, MD is a member of the following medical societies: Alpha Omega Alpha and American Urological Association
Disclosure: Nothing to disclose.

Matthew L Steinway, MD, Staff Physician, Department of Urology, University Hospitals of Cleveland, Case Western Reserve University
Matthew L Steinway, MD is a member of the following medical societies: American College of Surgeons, American Urological Association, and Endourological Society
Disclosure: Nothing to disclose.

Adrian H Feng, MD, Consulting Staff, Department of Urology, Urology Associates LTD
Adrian H Feng, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Gamal Mostafa Ghoniem, MD, FACS, Fellowship Program Director, Clinical Professor of Surgery, Head, Section of Voiding Dysfunction, Female Urology and Reconstruction, Cleveland Clinic Florida
Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Society for Urology and Engineering, and Society of University Urologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center
J Stuart Wolf, Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Bradley Fields Schwartz, DO, FACS, Associate 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 Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

 
 
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