Introduction

We have previously reported that elevated pre-cystectomy serum levels of epithelial tumor markers (TM) and lack of TM response to neoadjuvant chemotherapy (NAChT) are associated with worse oncological outcome in patients with invasive urothelial bladder cancer (UBC). Herein, we evaluate elevation of TM levels during follow-up and their predictive role in tumor recurrence. _x000D_

Methods

Under IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 409 patients with invasive UBC between August 2011 and August 2016. Excluded from the study were metastatic (13), palliative or inoperable (5) cases. Markers were measured at different time points during follow-up.

Results

A total of 391 cystectomy patients were included in the study with median age of 71 years and 79% males. Pathology was organ-confined in 59% and NAChT was given in 35% of population. Elevated precystectomy level of any of the tumor markers (31% of patients) was independently associated with worse RFS (p<0.001; HR=2.81) and OS (p<0.001; HR=3.97). After completion of cystectomy, we were able to document normal serum marker levels from 288 cases, of whom 26 patients (9%) developed tumor marker relapse later during follow up. This subset showed significantly more clinical recurrences (89% in elevated vs. 12% in stable group, RR= 7.41), and death (24% vs. 7%, RR=3.4). Median time from tumor marker relapse to clinical recurrence was 46 days (IQR 0-179), and median time to mortality was 308 days (IQR 119-574). Details of tumor markers course in the 23 patients with marker relapse followed by clinical recurrence is shown in figure 1. Further Survival analysis using landmark time-point with log rank showed there is a significant difference in cancer-specific survival between the groups (median 284 vs 547 days; p=0.01) (Figure 2).

Conclusions

To our knowledge, this is the first pilot study showing predictive role of epithelial tumor marker for recurrence of invasive urothelial bladder cancer. Patients with marker relapse following cystectomy are at significant increased risk of recurrence and mortality. A larger, controlled study with longer follow up is needed to determine their role in predicting survival.

Funding

None