Bladder cancer studies help pinpoint risk of recurrence

Among the excellent papers on the basic science, diagnosis, and treatment of bladder cancer presented at the AUA meeting, a number of important take-home messages emerged on disease recurrence, providing urologists with guidance in how aggressive to be with monitoring and subsequent treatment.

Patients with two or more recurrences of superficial bladder tumors, with an average of <12 months for recurrence, are at higher risk of developing an upper urinary tract cancer. Patients in lower-risk groups can forgo upper tract imaging.

The specter of upper tract transitional cell carcinoma in patients who have had a diagnosis of bladder cancer has prompted a number of protocols for upper tract monitoring. The most stringent is that of annual intravenous pyelography. However, the risk of upper tract tumors overall is in the range of 4% to 5% in the bladder cancer population.

Among men undergoing radical cystectomy with TCC of the bladder, urethral tumor recurrence occurs in 7% overall, but those undergoing orthotopic diversion and those without any prostate involvement demonstrate a significantly lower incidence.

The possibility of TCC in the retained urethra after cystectomy has prompted various protocols to identify the risk for this event.

Although not a contraindication to orthotopic bladder construction, prostatic stromal involvement by tumor increases the risk of urethral occurrences. While patients with orthotopic bladder replacement have an overall lower incidence of urethral cancer than those having ileal conduit diversion, careful questioning about urethral spotting or discomfort warrants urethroscopy. Periodic voided urine for cytology yielding positive results would also warrant urethroscopy.

For patients with an intact bladder, careful urethroscopy at the time of cystoscopy is a mandatory step in the assessment protocol. For patients with recurrent bladder cancer, specifically carcinoma in situ, biopsy of the prostatic urethra should be considered.

The fluorescent in situ hybridization (FISH) assay detected all invasive and in-situ TCCs of the bladder in a study of patients followed for TCC.

Cystoscopic evaluation in follow-up of TCC of the bladder remains the gold standard for detection and subsequent treatment of recurrent tumor. However, this is an invasive procedure. For the 500,000-plus patients with a history of TCC that are currently assessed with cystoscopy, a noninvasive urine test that is both sensitive and specific for both low- and high-grade tumors represents one of the holy grails of urothelial cancer management.

Cytology is very specific, but lacks sensitivity, specifically for low- and intermediate-grade tumors. FISH identifies chromosomal amplifications and deletions that are associated with urothelial neoplasia.

FISH operating characteristics are more favorable than cytology, specifically with regard to better sensitivities for low- and intermediate-range tumors while maintaining a high specificity. It also provides a lead time before detection of clinical recurrence. This study found that a positive FISH assay, when urine cytology was negative or atypical, predicted subsequent tumor occurrence in 36% of grade I/II Ta TCC; 100% ŽT1 TCC; and 100% carcinoma in situ. However, FISH is one of the most costly urine detection assays.

Patients undergoing transurethral resection plus one immediate postoperative instillation of chemotherapy show a 39% lower rate of recurrence than patients who receive TUR alone.

TCC of the bladder is notorious for tumor recurrence or "new tumor occurrences." The mechanism is based on both a field disease theory of panurothelial dysplasia or implantation on the traumatized areas of urothelium by tumor cells that have been released into the fluid-filled bladder at the time of resection. Theoretically, implantation can be prevented by the instillation of the chemotherapeutic regimen immediately after the procedure to negate the ability of dislodged tumor cells to adhere, implant, and multiply.

Numerous clinical trials have shown that patients receiving immediate instillation of chemotherapy after resection reduces the incidence of recurrence when compared with controls not receiving chemotherapeutic instillation.