Introduction

Management of T1 bladder cancer (T1-BC) is a therapeutic challenge. Tumor grade is an important prognostic factor to aid in treatment decision making. Currently, the AUA guidelines advise use of WHO 2004 grade over the 1973 classification, although in the literature, neither has been proven superior over the other. In this study, we compared the prognostic value of these WHO classifications in T1-BC.

Methods

Three uro-pathologists revised the slides of 601 primary (first diagnosis) T1-BCs from patients treated with BCG in four university hospitals between 1983 and 2006. Grade was defined according to WHO 1973 (grade 1-3) and 2004 (low-grade; LG and high-grade; HG). Association with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed for each system with multivariable cox-regression models. We corrected for age, sex, multiplicity, size (>3cm vs. ≤3 cm) and concomitant CIS.

Results

Median age was 71 (IQR 15) years and 196/601 (33%) tumors had concomitant CIS. After revision, 188 (31%) tumors were grade 2 and 413 (69%) grade 3 (WHO 1973). According to WHO 2004, 47 (8%) tumors were LG and 554 (92%) were HG. At a median follow-up of 5.9 (IQR 3.0) years, progression (≥cT2 and/or N1 and/or M1) occurred in 148 (25%) patients and 94 (16%) patients died of BC. Grade 3 tumors were associated with a worse PFS (HR 2.1, p<0.001) and CSS (HR 3.4, p<0.001) than grade 2 tumors. WHO 2004 grade had no prognostic value for progression (HG vs. LG HR 2.0, p=0.077) or CSS (HG vs. LG HR 1.6, p=0.292). The only prognostic factor for progression on multivariable analysis was WHO 1973 grade (HR 2.0, p=0.001). Grade 3 tumors (HR 3.0, p<0.001), increasing age (HR 1.03, p=0.003) and tumor size >3cm (HR 1.8, p=0.008) were all independently associated with worse CSS.

Conclusions

In T1-BC, WHO 1973 grade has a strong prognostic value, whereas the 2004 system is not prognostic. The superior value of WHO 1973 grade in T1-BC suggests that the 1973 system should be recommended by clinical non-muscle-invasive BC guidelines.

Funding

None