Predicting risk of multiple levels of recurrence and progression after initial diagnosis of nonmuscle-invasive bladder cancer in a multisite, community-based cohort

Background: Nonmuscle-invasive bladder cancer (NMIBC) has heterogeneous recurrence and progression outcomes. Available risk calculators estimate recurrence and progression but do not predict the recurrence stage or grade, which may influence downstream treatment. The objective of this study was to predict risk-stratified NMIBC recurrence and progression based on recurrence tumor classification and grade.

Methods: In total, 2956 patients with NMIBC (<T2) who were diagnosed at Kaiser Permanente Northwest and Geisinger from 1994 to 2015 were identified. Recurrences were annotated for tumor classification and grade. Four risk-stratified outcomes were created based on the tumor classification and grade of the recurrence: 1) any recurrence, 2) intermediate-risk recurrence (Ta high grade, carcinoma in situ, T1 low grade) or higher, 3) high-risk recurrence (T1 high grade) or progression (clinical T2), and 4) progression. Multivariable Cox proportional hazards regression was used to compute 1-year and 5-year risk estimates for each outcome based on initial tumor classification and grade.

Results: Over a median follow-up of 29.4 months, there were 1062 recurrences (35.9%), including 111 progressions (3.8%). The adjusted hazard of high-risk recurrence or progression increased, depending on initial tumor classification and grade: The adjusted hazard ratio was 2.60 (95% CI, 1.62-4.15) for Ta high-grade tumors, 4.74 (95% CI, 3.01-7.47) for tumor in situ or Ta with carcinoma in situ, and 7.14 (95% CI, 4.97-10.26) T1 high-grade tumors. Using Ta high-grade tumors as an example, the 1-year and 5-year predicted rates of adjusted risk of a high-risk recurrence or progression were 4.4% and 7.9%, respectively.

Conclusions: The 1-year and 5-year predicted risk of high-risk recurrences and progression increased with higher tumor classification and grade at diagnosis. These granular risk estimates may further inform risk-stratified treatment and surveillance for patients with NMIBC.