What is the role of lab tests in the preoperative workup of partial cystectomy?

Updated: Apr 03, 2019
  • Author: E Jason Abel, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Answer

Laboratory evaluation is performed for diagnosis and surgical preparation. Diagnostic laboratory evaluation for urothelial cancer may include 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 human interpretation and varying sensitivity. Urine cytology relies on a trained pathologist for examination. Thus, low-grade well-differentiated urothelial tumor cells that appear cytologically normal can contribute to a false negative rate of approximately 20%. In addition, well-differentiated tumors are thought to be more cohesive; thus cytology has a lower yield. For these low-grade well-differentiated tumors, cytology sensitivity can range from 35-65%. Conversely, for high-grade urothelial tumors, cytology can be highly specific and have very few false negative results. The false positive rate for urine cytology is approximately 1-12%, mostly due to urothelial atypia, inflammation, or changes associated with chemotherapy or radiation.

The search for more sensitive and specific urothelial tumor markers with the goal of decreasing the need for invasive procedures has led to the development of multiple molecular biology–based tests. These include tests targeting bladder tumor antigen (BTA) (BTA stat test and BTA TRAK test), nuclear matrix protein 22 (NMP-22), fibrin degradation products (FDPs), telomerase, hyaluronic acid and hyaluronidase, cytokeratins, Lewis X antigen, vascular endothelial growth factor (VEGF), soluble Fas, and surviving. Other tests include microsatellite analyses, fluorescent in situ hybridization (FISH) assays, and immunocytologic tests. Of these numerous markers under investigation, 6 are currently FDA approved for bladder cancer surveillance, including BTA, ImmunoCyt, NMP-22, and FISH.

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 (VEGF) to support angiogenesis. VEGF 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 FDPs have been observed in patients with bladder cancer.

Multiple chromosome alterations have been associated 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 urothelial cancer.

ImmunoCyt is an immunocytochemistry assay that utilizes a mixture of 3 monoclonal antibodies that can detect bladder tumor cells in the urine.

Although most of the new tumor markers yield a better sensitivity than conventional urinary cytology, their specificity is not as good as conventional methods. A recent comparison of the urinary markers reported a sensitivity of 12-85% for cytology, 53-78% for BTA-Stat, 51-100% for BTA-TRAK, 50-65% for NMP-22, 50-65% for ImmunoCyt, and 69-100% for FISH.

The same study reported specificity of 78-100% for cytology, 69-87% for BTA-Stat, 73-93% for BTA-Trak, 60-95% for NMP-22, 62-78% for ImmunoCyt, and 65-96% for FISH. Some promising investigational tests are underway for telomerase and BLCA-4. BLCA-4 is a nuclear matrix protein with early reports suggesting it may have both high sensitivity and specificity for bladder cancer (96% and 81-100%, respectively). [19, 20]

New urine tumor markers have shown potential for clinical utility in screening for bladder cancer and potentially even diagnosing or predicting recurrence, but their high cost and lower specificity place them in a limited role. Often they are used in combination with cytology to add diagnostic dimensions, but they have not replaced the need for cystoscopy.

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 assess renal function.

Blood reserves and bleeding risk can be determined by a complete blood count, prothrombin time, and activated partial thromboplastin time.

Presence of infection can be investigated with a white blood cell count, urinalysis, and culture.

Liver function tests and alkaline phosphatase may be suggestive of liver and bone metastases.

A baseline EKG can help identify underlying arrhythmias. For patients at high surgical risk, cardiac clearance may be warranted.


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