Bladder cancer detection: Multiple tumor markers ideal

San Francisco-Interim results from a long-term study of active and former chemical industry workers suggest that tumor markers in urine may emerge as a practical and reliable noninvasive diagnostic for bladder cancer.

After 6 years of screening, a combination of three markers emerged as the most accurate indication of asymptomatic bladder cancer.

"We cannot recommend the use of one marker over another," said study co-author Karl-Dietrich Sievert, MD, professor and vice-chairman of the department of urology at Eberhard-Karls University, Tubingen, Germany. "For now, we need a combination of markers to identify hidden bladder cancers. We need to develop better tests."

Approximately 91% of 1,772 eligible current and former chemical workers have enrolled in UroScreen, a total of 1,611 participants. Annual bladder cancer screening began in 2003 and included urine samples for cytology; chromosomal aberrations evaluated by the UroVysion test (Abbott Laboratories, Abbott Park, IL); quantitative measures of nuclear matrix protein 22 (NMP22 BladderChek test, Matritech, Inc., Newton, MA); by immunoassay; and assessment for microhematuria. Cystoscopy was recommended if one or more of the assays were positive. Additionally, survivin was analyzed by mRNA assay. The mean age of participants in the study was 58 years.

Between September 2003 and September 2009, there were a total of 6,391 preventive check-ups among the 1,611 UroScreen participants. Within the group, 290 individuals had one or more positive tumor markers, including positive cytology (five), polyploid cells on UroVysion (57), NMP22 (209), or survivin (138). There were 19 participants with positive UroVysion plus cytology and/or NMP22 results. Of the 290 individuals with positive markers, 182 had volunteered for cystoscopy as of September 2009.

Within the cystoscopy group, there were nine bladder carcinomas and two bladder papillomas, and four of the tumor patients had evidence of hematuria. Cystoscopy also found six bladder tumors and one papilloma in patients who were negative for cytology, UroVysion, and NMP22.

Hematuria 'most consistent' indicator

Hematuria is the single most consistent tumor indicator, Dr. Sievert said, but neither hematuria nor any other single tumor marker appeared as a reliable diagnostic tool. The combination of two or more markers was a more consistent indicator of the presence of bladder cancer while hematuria plus one or more tumor markers was still more indicative of the presence of a bladder tumor.

Tumor markers for bladder cancer are important to both Germany's public health insurance system and to the German Social Accident Insurance, which is responsible for the cost of treating work-related cancers. Payers are particularly interested in developing reliable tumor markers, Dr. Sievert noted, because early detection yields better cure rates and lowers overall costs of care.

"We need to keep pushing the medical industry to develop these tests and provide clinically useful markers," he said.

Funding for the study was provided by Abbott, Matritech, and Fujirebio Diagnostics Inc.