Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation for Bladder Cancer

Publication date: Available online 23 January 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Brian C. Baumann, Jiwei He, Wei-Ting Hwang, Kai N. Tucker, Justin E. Bekelman, Harry W. Herr, Seth P. Lerner, Thomas J. Guzzo, S. Bruce Malkowicz, John P. Christodouleas
Purpose/ObjectivesTo inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a local-regional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may impact the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials due to early disease progression, death, or loss to follow-up shortly after cystectomy; bias due to different statistical methodologies to estimate LF; and subgrouping bias due to different definitions of the LF subgroups.Methods and MaterialsThe LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy +/- chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses.ResultsYear of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. Using more stringent inclusion criteria, 26 SWOG patients (10%) and 60 (14%) from the single-institution cohort were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risk with 3-year rates of 7%, 17%, and 36%, respectively (p<0.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated.ConclusionsThese sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.

Teaser

To inform trials of adjuvant radiotherapy for bladder cancer, a local-regional failure (LF) risk stratification was developed. We assessed the impact of multiple potential biases on the model's validity for predicting outcomes. The predictions were not invalidated by time bias from evolving surgical techniques, use of different statistical methods to estimate LF risk, subgrouping bias due to differing definitions for the LF subgroups, or trial accrual bias from including patients ineligible for adjuvant RT trials.


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