Originally published as JCO Early Release 10.1200/JCO.2008.16.5951 on March 30 2009

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Grade and Stage at Presentation Do Not Predict Mortality in Patients With Bladder Cancer Who Survive Their Disease

From the Departments of Urology and Biostatistics, University of Rochester, Rochester, NY; State of Wisconsin Department of Health; and Departments of Pathology, Preventative Medicine, and Surgery, University of Wisconsin, Madison, WI.

Corresponding author: Edward M. Messing, MD, University of Rochester, School of Medicine and Dentistry, Department of Urology, 601 Elmwood Ave, Box 656, Rochester, NY 14642; e-mail: edward_messing{at}urmc.rochester.edu.

Purpose Our goal was to determine whether presenting grade and stage of bladder cancer (BC), which directly affect disease-specific survival, also influence time to and cause of non-BC deaths.

Methods Histology slides of all men who lived in Wisconsin age 50 years diagnosed with BC in 1988 were reviewed centrally, and time and cause of death as reported to the state's tumor registry were recorded. Competing risks analyses based on grade, tumor stage, and age at diagnosis were generated to correlate time and causes of death (BC or non-BC) with tumor histology and age at presentation.

Results Grade-stage categories were assigned to 509 patients with BC as follows: LGN = low grade (grade 1 or 2), nonmuscle invading (stage Ta or T1); HGN = high grade (grade 3 or carcinoma in situ), nonmucle invading (stage Ta, T1, or TIS); and INV = any grade, muscle invasive ( stage T2). Three hundred nine patients (60.7%) were LGN, 80 (15.7%) were HGN, and 120 (23.6%) were INV. Grade-stage category predicted overall (P = .0001) and BC-specific (P < .0001) mortality but not non-BC mortality (P = .72), with hazard ratios of 1.095 (95% CI, 0.783 to 1.531) for HGN versus LGN, 1.137 (95% CI, 0.799 to 1.617) for INV versus LGN, and 1.038 (95% CI, 0.670 to 1.607) for INV versus HGN. Age had a highly significant effect on overall and non-BC deaths (P < .0001) but only marginally predicted BC deaths (P = .054). Time to non-BC death did not differ significantly between grade-stage category (P = .12) or cause of death (P = .81).

Conclusion Grade-stage category at diagnosis predicts overall and BC mortality but not mortality from other causes. Thus, particularly for INV disease, because BC represents the major threat to life, aggressive therapies that have been shown to be effective are justified.

Supported in part by an Empire State Grant (New York State). The state of Wisconsin supported the original study design and implementation including requesting and reviewing pathology slides, assigning stage and grade, and correlating with a given patient (blinded to investigators). The Empire State Grant (R.M.) helped support the collection and management of data and assisted in its analysis. The Ashley Family Foundation supported, in part, the analysis and interpretation of data and preparation and review of manuscript.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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