The relationship between serial measurements of the level of a bladder tumor associated antigen and the potential for recurrence

Purpose: We evaluate the relationship between a serially assessed quantitat ive diagnostic marker (QDM) and the hazard function for the diagnosis of re currence of bladder cancer. The marker is based on a bladder tumor associat ed antigen (BTA TRAK*) assay. We present a rigorous approach to the evaluat ion of diagnostic markers to be used for recurrence monitoring. Materials and Methods: Archival voided urine samples serially collected fro m 187 patients with a prior diagnosis of transitional cell carcinoma of the bladder were measured for BTA TRAK, an assay performed in clinical laborat ories. Al patients had been treated for stage Ta or T1 transitional cell ca rcinoma and were undergoing periodic assessments for recurrence. The result s from the QDM were not used in case management. Time to histologically con firmed recurrence of transitional cell carcinoma was modeled using proporti onal hazard regression with the serial measurements of QDM, levels and othe r variables as covariates. QDM levels are in the model as a time dependent covariate on the base 10 logarithmic scale. Results: The estimated hazard ratio for QDM level indicated a 60% increase in the hazard for the diagnosis of recurrence for each 10-fold increment in the marker level (p = 0.013). Conclusions: A statistically significant relationship between the serially assessed QDM levels and the hazard for the diagnosis of recurrence has been established but the definition of optimum strategies for use of this relat ionship in clinical practice will require further study. Meanwhile, a prude nt action based on the statistical relationship would be to shorten surveil lance intervals for patients with high QDM levels.