Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome

Abstract

What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome.

Objectives: To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC.

Patients and methods: Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed.

Results: Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38-0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001).

Conclusions: Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.